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2,332,600 | Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block. | Although signs of sympathetic blockade following interscalene brachial plexus block include Horner's syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block.</AbstractText>Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg(-1)) followed by a continuous infusion (0.25 mg kg(-1) h(-1)). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end-inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation.</AbstractText>Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp-induced cutaneous vasoconstrictor and heat-induced vasodilator responses were attenuated.</AbstractText>Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.</AbstractText> |
2,332,601 | Block of sodium channels by divalent mercury: role of specific cysteinyl residues in the P-loop region. | Divalent mercury (Hg(2+)) blocked human skeletal Na(+) channels (hSkM1) in a stable dose-dependent manner (K(d) = 0.96 microM) in the absence of reducing agent. Dithiothreitol (DTT) significantly prevented Hg(2+) block of hSkM1, and Hg(2+) block was also readily reversed by DTT. Both thimerosal and 2,2'-dithiodipyridine had little effect on hSkM1; however, pretreatment with thimerosal attenuated Hg(2+) block of hSkM1. Y401C+E758C rat skeletal muscle Na(+) channels (mu1) that form a disulfide bond spontaneously between two cysteines at the 401 and 758 positions showed a significantly lower sensitivity to Hg(2+) (K(d) = 18 microM). However, Y401C+E758C mu1 after reduction with DTT had a significantly higher sensitivity to Hg(2+) (K(d) = 0.36 microM) than wild-type hSkM1. Mutants C753Amu1 (K(d) = 8.47 microM) or C1521A mu1 (K(d) = 8.63 microM) exhibited significantly lower sensitivity to Hg(2+) than did wild-type hSkM1, suggesting that these two conserved cysteinyl residues of the P-loop region may play an important role in the Hg(2+) block of the hSkM1 isoform. The heart Na(+) channel (hH1) was significantly more sensitive to low-dose Hg(2+) (K(d) = 0.43 microM) than was hSkM1. The C373Y hH1 mutant exhibited higher resistance (K(d) = 1.12 microM) to Hg(2+) than did wild-type hH1. In summary, Hg(2+) probably inhibits the muscle Na(+) channels at more than one cysteinyl residue in the Na(+) channel P-loop region. Hg(2+) exhibits a lower K(d) value (<1. 23 microM) for inhibition by forming a sulfur-Hg-sulfur bridge, as compared to reaction at a single cysteinyl residue with a higher K(d) value (>8.47 microM) by forming sulfur-Hg(+) covalently. The heart Na(+) channel isoform with more than two cysteinyl residues in the P-loop region exhibits an extremely high sensitivity (K(d) < 0. 43 microM) to Hg(+), accounting for heart-specific high sensitivity to the divalent mercury. |
2,332,602 | The anesthetic and recovery profile of two doses (60 and 80 mg) of plain mepivacaine for ambulatory spinal anesthesia. | Reports of transient neurological symptoms with the use of subarachnoid lidocaine has generated interest in alternate local anesthetics of intermediate duration, such as mepivacaine. This prospective randomized, double-blinded, dose-response study examined the anesthetic and recovery profiles of 60- and 80-mg doses of preservative-free plain mepivacaine for ambulatory spinal anesthesia. Sixty patients undergoing ambulatory anterior cruciate ligament repair of the knee under spinal anesthesia were randomized into two groups; Group 1 (29 patients) received 4 mL of 1.5% (60-mg dose) and Group 2 (31 patients) received 4 mL of 2% (80-mg dose) of plain mepivacaine. All patients received a combined spinal-epidural anesthetic technique. The epidural catheter was used only in the event the surgery outlasted the duration of surgical anesthesia with subarachnoid mepivacaine. Epidural supplementation was administered in three patients (12%) in Group 1 and one patient (3%) in Group 2 when the sensory block regressed to L-1 with surgery expected to last longer than 15 min. The cephalad dermatome level of the block and degree of motor block was comparable in the two groups. Times to two-segment and T-10 regression were comparable in the two groups (112 +/- 26 min in Group 1 versus 122 +/- 28 min in Group 2). Time to L-1 regression was significantly longer in Group 2 (146 +/- 28 min in Group 1 versus 159 +/- 19 min in Group 2). All of the ambulatory milestones were significantly faster in Group 1. Side effects, such as hypotension and emesis were negligible, severe bradycardia and urinary retention did not occur, and none of the patients in the two groups reported transient neurological symptoms over 24 h. In conclusion, plain mepivacaine in a 60- or 80-mg dose is a suitable local anesthetic choice for ambulatory spinal anesthesia with respect to anesthetic, as well as recovery profiles.</AbstractText>We evaluated the anesthetic and recovery profiles of 60- and 80-mg doses of plain mepivacaine for ambulatory spinal anesthesia. Both doses produced comparable sensory and motor block. Sensory and motor regression and ambulatory milestones were 20-30 min longer with the 80-mg dose. Side effects were negligible and transient neurological symptoms were not reported during a 24-h follow-up.</AbstractText> |
2,332,603 | Comparison of ropivacaine 0.1%-fentanyl and bupivacaine 0.125%-- fentanyl infusions for epidural labour analgesia. | To compare analgesic efficacies of ropivacaine-fentanyl and bupivacaine-fentanyl infusions for labour epidural analgesia.</AbstractText>In this double- blind, randomized study 100, term, nulliparous women were enrolled. Lumbar epidural analgesia (LEA) was started at cervical dilatation < 5 cm using either bupivacaine 0.25% followed by bupivacaine 0.125% + 2 microg x ml(-1) fentanyl infusion (n=50) or ropivacaine 0.2% followed by ropivacaine 0.1% + 2 microg x ml(-1) fentanyl infusion (n=50). Every hour maternal vital signs, visual analog scale (VAS) pain score, sensory levels, and motor block (Bromage score) were assessed. Data were expressed as mean +/-1 SD and analyzed using Chi -Squared and Mann-Whitney U tests at <0.05.</AbstractText>The onset times were 10.62+/-4.9 and 11.3+/-4.7 min for the bupivacaine and ropivacaine groups respectively (P = NS). The median VAS scores were not different between the groups at any of the evaluation periods. However, at least 80% of patients in the ropivacaine group had no demonstrable motor block after the first hour compared with only 55% of patients given bupivacaine (P =0.01).</AbstractText>Both bupivacaine and ropivacaine produce satisfactory labour analgesia. However, ropivacaine infusion is associated with less motor block throughout the first stage of labour and at 10 cm dilatation.</AbstractText> |
2,332,604 | [Endothelins and chronic cardiac insufficiency]. | Endothelins (ET) comprise a group of substances which are produced and have regulatory functions in different systems of the organism. The main cardiovascular ET is ET-1 which is so far the most potent vasoconstrictor substance. In the pathophysiology of cardiac insufficiency ET-1 promotes cardiac hypertrophy, is involved in vasoconstriction, delayed relaxation and reduced left ventricular contractility. The ET-1 level correlates with pulmonary vascular hypertension. By vasoconstriction of renal arteries ET leads to volume retention. Big-ET is a very efficient neurohumoral marker in the diagnosis of developed cardiac failure which can lead to more accurate prognostic stratification. ET-1 is probably important for assessment of the diagnosis of cardiac insufficiency only in severe cardiac failure. The favourable effect of ET block in cardiac insufficiency was proved for the non-selective ETA/ETB blocker and selective ETA blocker. The selective ETB blocker has an adverse haemodynamic effect in treatment of heart failure but by suppression of aldosterone it can prevent fluid retention. In the treatment of cardiac failure blockers of endothelin converting enzyme seem perspective as they reduce adversely activated neurohumoral factors. |
2,332,605 | Inducible nitric oxide synthase mediates delayed myocardial protection induced by activation of adenosine A(1) receptors: evidence from gene-knockout mice. | The mechanism of delayed preconditioning induced by activation of adenosine A(1) receptors (A(1)ARs) is not fully understood. We determined the role of inducible nitric oxide synthase (iNOS) in mediating adenosine-induced late cardioprotection using pharmacological inhibitors and iNOS gene-knockout mice.</AbstractText>Adult male mice were treated with saline or an A(1)AR agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA). Twenty-four hours later, the hearts were perfused in Langendorff mode and subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 mg/kg IP) and S-methylisothiourea (SMT; 3 mg/kg IP) were used to block A(1)ARs and iNOS, respectively. Infarct size (IS) was measured by triphenyltetrazolium chloride staining, and iNOS expression was measured by Western blots. Myocardial IS was reduced from 24.0+/-3. 2% in the saline group to 12.2+/-2.5% in CCPA-treated mice (P<0.05). The infarct-reducing effect of CCPA was abrogated by DPCPX (29.3+/-3. 4%) and SMT (32.3+/-2.6%) and was absent in mice with targeted ablation of iNOS (23.9+/-1.6%). CCPA produced improvement in postischemic end-diastolic pressure, developed pressure, and rate-pressure product, which was also blocked by DPCPX and SMT. Increased iNOS protein expression observed in CCPA-treated hearts was diminished by DPCPX.</AbstractText>Selective activation of A(1)ARs produces delayed cardioprotection against ischemia/reperfusion injury in the mouse. Increased iNOS expression concomitant with the lack of protective effect of A(1)AR activation in iNOS gene-knockout mice suggests a direct cause-and-effect relationship of iNOS in adenosine-induced late cardioprotection.</AbstractText> |
2,332,606 | Barnidipine block of L-type Ca(2+) channel currents in rat ventricular cardiomyocytes. | The effects of barnidipine and nifedipine on L-type Ca(2+) current (I(Ca(L))) were investigated in ventricular cardiomyocytes from rats. Both barnidipine and nifedipine reduced I(Ca(L)) in a concentration and voltage dependent manner; the EC(50) were 80 and 130 nM at a holding potential of -80 mV, respectively, and 18 and 6 nM at -40 mV, respectively. Both drugs induced a leftward shift of the steady-state inactivation curve of I(Ca(L)). Using a twin pulse protocol, the relationships between the amount of block of I(Ca(L)) by either drug, seen during the second pulse, and the length of the first pulse were described by monoexponential functions reflecting onset of block, dependent on drug concentration. The onset of block by barnidipine was three times faster than that by nifedipine. With both drugs, recovery of I(Ca(L)) was 50 times slower than under control conditions and described by monoexponential functions reflecting offset of block (independent of drug concentration). The offset of block with barnidipine was three times slower than that with nifedipine. The time constants of block and unblock of I(Ca(L)) by both drugs were used to calculate binding and unbinding and to predict their effects at two frequencies. It is suggested that barnidipine exhibits a higher affinity to the inactivated Ca(2+) channel state as compared to nifedipine. |
2,332,607 | Differential effects of cyclosporine A, methylprednisolone, mycophenolate, and rapamycin on CD154 induction and requirement for NFkappaB: implications for tolerance induction. | Recent experimental data indicate that the targeting of the costimulatory molecule CD40-ligand (CD154) may well offer an opportunity for tolerance induction in transplant recipients and patients with autoimmune diseases, although the optimal therapeutic strategy for clinical application of CD154 monoclonal antibody (mAb) is unclear.</AbstractText>We undertook vascularized heterotopic cardiac allograft transplantation in completely MHC-mismatched mice, treated recipients with CD154 mAb plus various immunosuppressive agents, and performed flow cytometric analysis of CD154 expression by T cells activated in vitro in the presence of corresponding immunosuppressive agents. We also tested the extent to which CD154 induction was NFkappaB-dependent by using NFkappaB/p50-deficient mice as allograft recipients and as source of cells for in vitro studies of CD154 induction, and through use of proteasome inhibitors to block IkappaBalpha degradation and NFKB activation in wild-type mice.</AbstractText>Concomitant use of cyclosporin A or methylprednisolone, but not rapamycin or mycophenolate, inhibited CD154 mAb-induced allograft survival. The differential effects of these agents on CD154 mAb-induced tolerance correlated with their capacity to inhibit activation-induced CD154 expression on CD4+ T cells. Full expression of CD154 expression was found to require NF-kappaB activation, and CD154 mAb was ineffective in NF-kappaB/p50 deficient allograft recipients or control mice in which NF-kappaB activation was blocked by proteasome inhibition.</AbstractText>Strategies to use CD154 mAb clinically must take into account the effects of immunosuppressive agents on CD154 induction, which seems to be at least partially NF-kappaB dependent. Our data suggest that ligation of surface-expressed CD154 provides an important signal that modulates T cell activation and thereby contributes to the effects of CD154 mAb, in addition to previously recognized actions involving blockade of CD40/CD154-dependent cell activation and activation-induced cell death.</AbstractText> |
2,332,608 | Stereoselective interactions of the enantiomers of chromanol 293B with human voltage-gated potassium channels. | Selective inhibitors of the slow component of the cardiac delayed rectifier K(+) current, I(Ks), are of interest as novel class III antiarrhythmic agents and as tools for studying the physiologic roles of the I(Ks) current. Racemic chromanol 293B is an inhibitor of both native I(Ks) and its putative molecular counterpart, the KvLQT1+minK ion channel complex. We synthesized the (+)-[3S,4R] and (-)-[3R,4S] enantiomers of chromanol 293B using chiral intermediates of known absolute configuration and determined their relative potency to block recombinant human K(+) channels that form the basis for the major repolarizing K(+) currents in human heart, including KvLQT1+minK, human ether-a-go-go-related gene product (hERG), Kv1.5, and Kv4.3, corresponding to the slow (I(Ks)), rapid (I(Kr)), and ultrarapid (I(Kur)) delayed rectifier currents and the transient outward current (I(To)), respectively. K(+) channels were expressed in mammalian cells and currents were recorded using the whole-cell patch-clamp technique. We found that the physicochemical properties and relative potency of the enantiomers differed from those reported previously, with (-)-[3R,4S]293B nearly 7-fold more potent in block of KvLQT1+minK than (+)-[3S,4R]293B, indicating that the original stereochemical assignments were reversed. K(+) current inhibition by (-)-293B was selective for KvLQT1+minK over hERG, whereas the stereospecificity of block for KvLQT1+minK and Kv1.5 was preserved, with (-)-293B more potent than (+)-293B for both channel complexes. We conclude that the (-)-[3R,4S] enantiomer of chromanol 293B is a selective inhibitor of KvLQT1+minK and therefore a useful tool for studying I(Ks). |
2,332,609 | Link between heart disease, cholesterol, and Alzheimer's disease: a review. | Increased prevalence of Alzheimer's disease-like beta-amyloid deposits in the neuropil and within neurons occurs in the brains of non-demented individuals with heart disease. Heart disease is a prevalent finding in Alzheimer's disease, and may be a forerunner to the dementing disorder. In the cholesterol-fed rabbit model of human coronary heart disease there is production and accumulation of beta-amyloid in the brain. This accumulation of beta-amyloid can be reversed by removing cholesterol from the rabbits' diet. In culture cells, a cholesterol challenge has been shown to increase production of beta-amyloid, and dramatic reductions of cholesterol produced by HMG Co-A reductase inhibitors decrease production of beta-amyloid. Increased beta-amyloid production is also produced by dietary cholesterol in a number of transgenic mouse models of Alzheimer's disease. Administration of HMG Co-A reductase inhibitors may block beta-amyloid production caused by dietary cholesterol in rabbits. Clinical trials testing the benefit of HMG Co-A reductase inhibitors in the treatment of Alzheimer's disease are underway. |
2,332,610 | [Hemodynamic effects of spinal anesthesia with 2% lidocaine in comparison to 0.5% isobaric bupivacaine]. | Our study compared the haemodynamic changes after spinal anesthesia with 2% lignocaine and 0.5% plain bupivacaine.</AbstractText>A controlled, randomized trial was performed on 30 patients scheduled for arthroscopic knee surgery. 2% lignocaine and 0.5% plain bupivacaine were used for spinal anaesthesia. We measured cardiac output (electrical bioimpedance cardiography), blood pressure and development of sensory blockade before and for 25 minutes after spinal anaesthesia.</AbstractText>In patients developing a sensory block below T6 there were no differences between both anaesthetics in haemodynamic parameters. But in patients developing a sensory block at or above T6 there was a greater drop in mean arterial pressure and cardiac output and a faster decrease in heart rate for bupivacaine compared to patients receiving Lignocaine.</AbstractText>In patients developing a sensory block at or above the T6 dermatome, the decrease in cardiac output and mean arterial pressure in the first 25 min after spinal anaesthesia is smaller when 2% lignocaine rather than 0.5% bupivacaine is used for blockade.</AbstractText> |
2,332,611 | Low-affinity block of cardiac K(+) currents by nifedipine. | Nifedipine inhibits a variety of K(+) currents with IC(50) between 4 and 40 microM. Among the more sensitive of these are two types (transient outward and ultrarapid hKv1.5) found in the heart. To evaluate the actions of the drug on other prominent cardiac K(+) currents, guinea-pig ventricular myocytes were voltage-clamped for measurement of inwardly rectifying K(+) current (I(K1)), rapidly activating delayed-rectifier K(+) current (I(Kr)), and slowly activating delayed-rectifier K(+) current (I(Ks)). The currents were unaffected by < or =10 microM nifedipine, but inhibited by higher concentrations; IC(50) values were 260 microM for I(K1), 275 microM for I(Kr), and 360 microM for I(Ks). The time- and voltage-dependent properties of I(Ks) were unaffected by the drug, and full block was attained on the first depolarisation after a rest. The results establish that the sensitivity of I(Kr) and I(Ks) to inhibition by nifedipine is approximately 50 times lower than the sensitivity of other cardiac delayed-rectifier K(+) currents. |
2,332,612 | The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block. | Neonatal lupus erythematosus is caused by the transplacental passage of maternal autoantibodies. The aim of this study was to determine the risk of connective tissue disorders in mothers of children with cutaneous neonatal lupus erythematosus, as compared with the risk in mothers of children with congenital heart block, which is also often caused by maternal autoantibodies.</AbstractText>We prospectively studied all mothers of children with cutaneous neonatal lupus erythematosus during a 14-year period at the Hospital for Sick Children, Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for study. The health and antibody status of the mothers were determined at the birth of the child and at followup.</AbstractText>All mothers had anti-Ro antibodies at the time of birth. Initially 10 mothers were healthy and 14 mothers had either a defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital heart block were asymptomatic at follow-up (P <0.005).</AbstractText>The majority of mothers of children with cutaneous neonatal lupus erythematosus had a defined or undifferentiated autoimmune disorder at the time of the child's birth, and others developed these conditions during follow-up. The health of these mothers appears to differ from that of mothers of children with congenital heart block.</AbstractText> |
2,332,613 | Inhibition by nickel of the L-type Ca channel in guinea pig ventricular myocytes and effect of internal cAMP. | The characteristics of nickel (Ni) block of L-type Ca current (I(Ca, L)) were studied in whole cell patch-clamped guinea pig cardiac myocytes at 37 degrees C in the absence and presence of 100 microM cAMP in the pipette solution. Ni block of peak I(Ca,L) had a dissociation constant (K(d)) of 0.33 +/- 0.03 mM in the absence of cAMP, whereas in the presence of cAMP, the K(d) was 0.53 +/- 0.05 mM (P = 0.006). Ni blocked Ca entry via Ca channels (measured as I(Ca, L) integral over 50 ms) with similar kinetics (K(d) of 0.35 +/- 0.03 mM in cAMP-free solution and 0.30 +/- 0.02 mM in solution with cAMP, P = not significant). Under both conditions, 5 mM Ni produced a maximal block that was complete for the first pulse after application. Ni block of I(Ca,L) was largely use independent. Ni (0. 5 mM) induced a positive shift (4 to 6 mV) in the activation curve of I(Ca,L). The block of I(Ca,L) by 0.5 mM Ni was independent of prepulse membrane potential (over the range of -120 to -40 mV). Ni (0.5 mM) also induced a significant shift in I(Ca,L) inactivation: by 6 mV negative in cAMP-free solution and by 4 mV positive in cells dialyzed with 100 microM cAMP. These data suggest that, in addition to blocking channel conductance by binding to a site in the channel pore, Ni may bind to a second site that influences the voltage-dependent gating of the L-type Ca channel. They also suggest that Ca channel phosphorylation causes a conformational change that alters some effects of Ni. The results may be relevant to excitation-contraction coupling studies, which have employed internal cAMP dialysis, and where Ni has been used to block I(Ca,L) and Ca entry into cardiac cells. |
2,332,614 | Effects of forearm bier block with bretylium on the hemodynamic and metabolic responses to handgrip. | We tested the hypothesis that a reduction in sympathetic tone to exercising forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip protocol before and after forearm bier block with bretylium as forearm blood flow (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR indexes) and autonomic reflex responses (heart rate, blood pressure, and sympathetic nerve traffic) were measured. Bretylium inhibits the release of norepinephrine at the neurovascular junction. Bier block increased blood flow as well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02, respectively). However, despite this increase in flow, venous K(+) release and H(+) release were both increased during exercise (P < 0.002 for both indexes). Additionally, minimal muscle pH measured during the first minute of recovery with NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036, simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier block. The results support the conclusion that sympathetic stimulation to muscle during exercise not only limits muscle blood flow but also appears to limit anaerobiosis and H(+) release, presumably through a preferential recruitment of oxidative fibers. |
2,332,615 | Interleukin-1beta, Src- and non-Src tyrosine kinases, and nitric oxide synthase induction in rat aorta in vitro. | We studied the potential roles for endogenous interleukin-1beta (IL-1beta) and for several signaling pathways in the spontaneous induction in vitro of inducible nitric oxide synthase (iNOS) in endothelium-denuded rat aorta rings. Added IL-1beta augmented, whereas the IL-1beta receptor antagonist IL-1ra blocked, spontaneous iNOS induction. Furthermore, increases in IL-1beta mRNA preceded those of iNOS mRNA. Mitogen-activated protein kinase kinase and phosphatidyl inositol 3' kinase inhibition did not block iNOS induction, whereas nuclear factor kappaB inhibition did. The sarcoma virus tyrosine kinase (Src) family-selective inhibitor 4-amino-5(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) blocked the upregulation of IL-1beta mRNA and the subsequent induction of iNOS but not the induction of iNOS stimulated by exogenously added IL-1beta. In contrast, the non-Src inhibitors TP 47/AG 213 and genistein and the tyrosine phosphatase inhibitor vanadate did not affect the spontaneous upregulation of IL-1beta mRNA but blocked both the IL-1beta-mediated and spontaneous induction of iNOS. We conclude that 1) the upregulation of tissue IL-1beta, via a signaling pathway involving a Src family kinase, plays a key role in rat vascular iNOS induction and 2) non-Src tyrosine kinases play roles downstream from IL-1beta for iNOS induction. |
2,332,616 | PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation. | In this study we used an in vitro model of delayed preconditioning to investigate activation of mitogen-activated protein kinases (MAPKs) and their potential role in protection. Neonatal rat cardiomyocytes were preconditioned using a buffer containing glycolytic inhibitors and low pH (minimal metabolic preconditioning; MMPC) consisting of modified Krebs buffer, 10 mM 2-deoxyglucose, and 20 mM lactate, pH 6.8, for 2 h followed by 24 h of simulated reperfusion before lethal simulated ischemia (LSI). MAPK activation during the MMPC protocol was determined using phospho-specific antisera and the effect on protection determined following LSI. Rapid, transient phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 MAPK was observed during each of the MMPC, reperfusion, and LSI phases; an effect blocked by MAPK inhibitors PD-98059 and SB-203580, respectively, but not by the protein kinase C (PKC) inhibitor Ro31-8220. However, although MMPC was blocked by Ro31-8220, treatment with the MAPK inhibitors during the preconditioning protocol did not block delayed protection conferred by MMPC. Thus the data suggest that, in this model of delayed preconditioning, protection appears to be PKC dependent but independent of ERK1/2 or p38 MAPK activation. |
2,332,617 | Coronary artery bypass grafting in the conscious patient without endotracheal general anesthesia. | Over the past several years, considerable experience has accumulated in performing coronary anastomoses on the beating heart, and various aspects of minimally invasive approaches have been simplified. In an attempt to further simplify and decrease the "invasiveness" of this procedure, performing this operation without endotracheal general anesthesia was deemed feasible in certain subsets of patients.</AbstractText>Between October 1998 and June 1999, 5 patients underwent coronary artery bypass grafting without endotracheal general anesthesia, using high thoracic epidural block to construct extension grafts with a short segment of radial artery, between the in situ left or right internal thoracic arteries and the left anterior descending (n = 4) or right coronary arteries (n = 1). There were 2 female and 3 male patients, with a mean age of 67.4 +/- 8.3 years.</AbstractText>The perioperative course of the patients was uneventful. There was no perioperative morbidity or mortality. No patient was converted to general anesthesia or to conventional operation. Control angiograms revealed patent anastomoses in all patients. In 1 patient, spasm of the radial artery graft was observed that was relieved 3 weeks later spontaneously. Mean length of hospital stay was 2.2 +/- 0.4 days. All patients were symptom free and returned to normal daily life at the first postoperative month.</AbstractText>Our initial experience confirms the feasibility of performing coronary bypass grafting in the conscious patient without endotracheal general anesthesia.</AbstractText> |
2,332,618 | Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. | The transmembrane protein CD36 has been identified in isolated cell studies as a putative transporter of long chain fatty acids. In humans, an association between CD36 deficiency and defective myocardial uptake of the fatty acid analog 15-(p-iodophenyl)-3-(R, S)-methyl pentadecanoic acid (BMIPP) has been reported. To determine whether this association represents a causal link and to assess the physiological role of CD36, we compared tissue uptake and metabolism of two iodinated fatty acid analogs BMIPP and 15-(p-iodophenyl) pentadecanoic acid (IPPA) in CD36 null and wild type mice. We also investigated the uptake and lipid incorporation of palmitate by adipocytes isolated from both groups. Compared with wild type, uptake of BMIPP and IPPA was reduced in heart (50-80%), skeletal muscle (40-75%), and adipose tissues (60-70%) of null mice. The reduction was associated with a 50-68% decrease in label incorporation into triglycerides and in 2-3-fold accumulation of label in diglycerides. Identical results were obtained from studies of [(3)H]palmitate uptake in isolated adipocytes. The block in diglyceride to triglyceride conversion could not be explained by changes in specific activities of the key enzymes long chain acyl-CoA synthetase and diacylglycerol acyltransferase, which were similar in tissues from wild type and null mice. It is concluded that CD36 facilitates a large fraction of fatty acid uptake by heart, skeletal muscle, and adipose tissues and that CD36 deficiency in humans is the cause of the reported defect in myocardial BMIPP uptake. In CD36-expressing tissues, uptake regulates fatty acid esterification at the level of diacylglycerol acyltransferase by determining fatty acyl-CoA supply. The membrane transport step may represent an important control site for fatty acid metabolism in vivo. |
2,332,619 | Fast maximum entropy approximation in SPECT using the RBI-MAP algorithm. | In this work, we present a method for approximating constrained maximum entropy (ME) reconstructions of SPECT data with modifications to a block-iterative maximum a posteriori (MAP) algorithm. Maximum likelihood (ML)-based reconstruction algorithms require some form of noise smoothing. Constrained ME provides a more formal method of noise smoothing without requiring the user to select parameters. In the context of SPECT, constrained ME seeks the minimum-information image estimate among those whose projections are a given distance from the noisy measured data, with that distance determined by the magnitude of the Poisson noise. Images that meet the distance criterion are referred to as feasible images. We find that modeling of all principal degrading factors (attenuation, detector response, and scatter) in the reconstruction is critical because feasibility is not meaningful unless the projection model is as accurate as possible. Because the constrained ME solution is the same as a MAP solution for a particular value of the MAP weighting parameter, beta, the constrained ME solution can be found with a MAP algorithm if the correct value of beta is found. We show that the RBI-MAP algorithm, if used with a dynamic scheme for estimating beta, can approximate constrained ME solutions in 20 or fewer iterations. We compare results for various methods of achieving feasible images on a simulation of Tl-201 cardiac SPECT data. Results show that the RBI-MAP ME approximation provides images and quantitative estimates close to those from a slower algorithm that gives the true ME solution. Also, we find that the ME results have higher spatial resolution and greater high-frequency noise content than a feasibility-based stopping rule, feasibility-based low-pass filtering, and a quadratic Gibbs prior with beta selected according to the feasibility criterion. We conclude that fast ME approximation is possible using either RBI-MAP with the dynamic procedure or a feasibility-based stopping rule, and that such reconstructions may be particularly useful in applications where resolution is critical. |
2,332,620 | Effects of graded levels of potato by-products in barley- and corn-based beef feedlot diets: I. Feedlot performance, carcass traits, meat composition, and appearance. | To measure effects of diet on feedlot performance, carcass characteristics, and beef appearance, 144 crossbred beef steers (333+/-.44 kg) were allotted within weight block (3) to a randomized complete block design with a 2 x 3 factorial arrangement of dietary treatments. Main effects were grain (barley or corn) and level of potato by-product (PB) (0, 10, or 20% of diet DM). Steers were fed diets containing 83% concentrate (grain plus PB), 10% supplement, and 7% alfalfa on a DM basis for an average of 130 d. Level of PB quadratically affected (P < .10) DM intake and gain such that steers fed 10% PB ate more and gained faster. Corn-fed steers were more (P < .05) efficient (5.8 vs 6.3 kg DM/kg gain) and had more (P < .05) kidney, pelvic, and heart fat (2.2 vs 2.0%) than barley-fed steers. A grain x PB interaction was detected (P < .10) for marbling score, which was minimized in steers fed barley diets (small 0) but maximized in those fed corn diets (small 30) at 10% PB. Diet did not affect beef firmness or beef color score. Barley-fed beef had whiter fat (P < .05) than corn-fed beef (2.6 vs 2.9 on a 1 to 7 scale); however, fat luster score was not affected by diet. Small differences were noted in fatty acid profile, purge, drip loss, and muscle pH. No differences were noted in color measurements due to dietary treatment over 7 d of retail shelf life. Overall, differences were small and probably not biologically important. These results indicate that these diets had minimal effects on beef appearance and carcass characteristics, meat composition, and water retention properties. |
2,332,621 | Exercise induces lipoprotein lipase and GLUT-4 protein in muscle independent of adrenergic-receptor signaling. | Exercise increases the expression of lipoprotein lipase (LPL) and GLUT-4 in skeletal muscle. Intense exercise increases catecholamines, and catecholamines without exercise can affect the expression of both LPL and GLUT-4. To test the hypothesis that adrenergic-receptor signaling is central to the induction of LPL and GLUT-4 by exercise, six untrained individuals [age 28 +/- 4 (SD) yr, peak oxygen uptake 3.6 +/- 0.3 l/min] performed two exercise bouts within 12 days. Exercise consisted of cycling at approximately 65% peak oxygen uptake for 60 min with (block trial) and without (control trial) adrenergic-receptor blockade. Exercise intensity was the same during the block and control trials. Plasma catecholamine concentrations were significantly higher and heart rates were significantly lower during the block trial compared with the control trial, consistent with known effects of adrenergic-receptor blockade. However, blockade did not prevent the induction of either LPL or GLUT-4 proteins assayed in biopsies of skeletal muscle. LPL was significantly increased by 170-240% and GLUT-4 was significantly increased by 32-51% at 22 h after exercise compared with before exercise during both the control and block trials. These findings provide evidence that exercise increases muscle LPL and GLUT-4 protein content via signals generated by alterations in cellular homeostasis and not by adrenergic-receptor stimulation. |
2,332,622 | Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation. | Apoptosis has been implicated in ischemic heart disease, but its mechanism in cardiomyocytes has not been elucidated. In this study, we investigate the effects of hypoxia and reoxygenation in adult cardiomyocytes and the molecular mechanism involved in cardiomyocyte apoptosis. Morphologically, reoxygenation induced rounding up of the cells, appearance of membrane blebs that were filled with marginated mitochondria, and ultrastructural findings characteristic of apoptosis. Reoxygenation (18 hours of reoxygenation after 6 hours of hypoxia) and prolonged hypoxia (24 hours of hypoxia) resulted in a 59% and 51% decrease in cellular viability, respectively. During reoxygenation, cell death occurred predominantly via apoptosis associated with appearance of cytosolic cytochrome c and activation of caspase-3 and -9. However, nonapoptotic cell death predominated during prolonged hypoxia. Both caspase inhibition and Bcl-2 overexpression during reoxygenation significantly improved cellular viability through inhibition of apoptosis but had minimal effect on hypoxia-induced cell death. Bcl-2 overexpression blocked reoxygenation-induced cytochrome c release and activation of caspase -3 and -9, but caspase inhibition alone did not block cytochrome c release. These results suggest that apoptosis predominates in cardiomyocytes after reoxygenation through a mitochondrion-dependent apoptotic pathway, and Bcl-2 prevents reoxygenation-induced apoptosis by inhibiting cytochrome c release from the mitochondria and prevents activation of caspase-3 and -9. |
2,332,623 | [Combined subarachnoid-epidural technique for obstetric analgesia]. | Combined spinal-epidural blockade for labor pain has enjoyed increasing popularity in obstetric anesthesia. The usual procedure is to use a single space and a single needle for dural puncture, inserting a spinal needle through an epidural needle followed by insertion of a catheter. A small dose of one or several substances (usually a lipophilic opioid and a local anesthetic) is first injected in the intrathecal space to provide rapid, effective analgesia with minimal muscle blockade. The epidural catheter is used if labor lasts longer than the spinal block, if the spinal block is insufficient, or in case of cesarean section. Combined spinal-epidural blockade is a safe, valid alternative to conventional epidural analgesia and has become the main technique for providing obstetric analgesia in many hospitals. The most widely-recognized advantage of the technique is high maternal satisfaction with rapid and effective analgesia. Mobility of the lower extremities is preserved and the mother is often able to walk. Because opioids are injected into the intrathecal space and because the technique is more invasive than standard epidural analgesia, the potential risk to mother and fetus increases. |
2,332,624 | Comparison of L-type calcium channel blockade by nifedipine and/or cadmium in guinea pig ventricular myocytes. | We tested the assumption that nifedipine blocks L-type calcium current [I(Ca(L))] at +10 mV and unmasks Na(+)/Ca(2+) exchange-triggered contractions in guinea pig isolated ventricular myocytes. Voltage-clamp pulses elicited I(Ca(L)) at +10 mV and evoked contractions in myocytes superfused with Tyrode's solution (35 degrees C). Nifedipine blocked I(Ca(L)) with an IC(50) of 0.3 microM; this decreased to 50 nM at a holding potential of -40 mV, indicating preferential block of inactivated L-type Ca(2+) channels. Use-independent block of I(Ca(L)) increased with concentration (10-100 microM) and application time when nifedipine was rapidly applied (t(1/2) = approximately 0.2 s) during rest intervals (5-30 s). The fraction of use-dependent block of I(Ca(L)) diminished with increasing drug concentration. Nifedipine also accelerated I(Ca(L)) inactivation on the first test pulse. The combination of 30 microM nifedipine/30 microM Cd(2+) (Nif 30/Cd 30) was as effective as 100 microM nifedipine to suppress I(Ca(L)) on the first test pulse at +10 mV. The incidence of complete block of contractions, as for complete block of I(Ca(L)), increased as a function of nifedipine concentration and application time. Neither nifedipine nor Nif 30/Cd 30 affected Na(+)/Ca(2+) exchange current at +10 to +100 mV. Contractions at +100 mV, although as large as those at +10 mV, were delayed in onset and resistant to nifedipine or Nif 30/Cd 30. We conclude that nifedipine-sensitive I(Ca(L)) triggers contractions at +10 mV, whereas nifedipine-resistant Na(+)/Ca(2+) exchange current initiates those at +100 mV. |
2,332,625 | Coexpression with beta(1)-subunit modifies the kinetics and fatty acid block of hH1(alpha) Na(+) channels. | Voltage-gated cardiac Na(+) channels are composed of alpha- and beta(1)-subunits. In this study beta(1)-subunit was cotransfected with the alpha-subunit of the human cardiac Na(+) channel (hH1(alpha)) in human embryonic kidney (HEK293t) cells. The effects of this coexpression on the kinetics and fatty acid-induced suppression of Na(+) currents were assessed. Current density was significantly greater in HEK293t cells coexpressing alpha- and beta(1)-subunits (I(Na,alpha beta)) than in HEK293t cells expressing alpha-subunit alone (I(Na,alpha)). Compared with I(Na,alpha), the voltage-dependent inactivation and activation of I(Na,alpha beta) were significantly shifted in the depolarizing direction. In addition, coexpression with beta(1)-subunit prolonged the duration of recovery from inactivation. Eicosapentaenoic acid [EPA, C20:5(n-3)] significantly reduced I(Na,alpha beta) in a concentration-dependent manner and at 5 microM shifted the midpoint voltage of the steady-state inactivation by -22 +/- 1 mV. EPA also significantly accelerated channel transition from the resting state to the inactivated state and prolonged the recovery time from inactivation. Docosahexaenoic acid [C22:6(n-3)], alpha-linolenic acid [C18:3(n-3)], and conjugated linoleic acid [C18:2(n-6)] at 5 microM significantly inhibited both I(Na,alpha beta) and I(Na,alpha.) In contrast, saturated and monounsaturated fatty acids had no effects on I(Na,alpha beta). This finding differs from the results for I(Na,alpha), which was significantly inhibited by both saturated and unsaturated fatty acids. Our data demonstrate that functional association of beta(1)-subunit with hH1(alpha) modifies the kinetics and fatty acid block of the Na(+) channel. |
2,332,626 | Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans. | The expression of endothelial adhesion molecules and their functional significance in leukocyte adhesion to human myocardial blood vessels in acute myocardial infarction (AMI) were studied.</AbstractText>Leukocyte extravasation, mediated by specific adhesion molecules, exacerbates tissue injury after restoration of blood supply to an ischemic tissue. Experimental myocardial reperfusion injury can be alleviated with antibodies that block the function of adhesion molecules involved in leukocyte emigration, but the relevant molecules remain poorly characterized in human AMI.</AbstractText>Semiquantitative immunohistochemistry and in vitro adhesion assays were used to study the expression and granulocyte binding abilities of different endothelial adhesion molecules in human AMI. Changes in the molecular nature of vascular adhesion protein-1 (VAP-1) were evaluated using immunoblotting.</AbstractText>Certain endothelial adhesion molecules (intercellular adhesion molecule [ICAM-2], CD31 and CD73) were expressed in myocardial blood vessels homogeneously in normal and ischemic hearts, whereas others (E-selectin and peripheral lymph node addressin) were completely absent from all specimens. The synthesis of ICAM-1 was locally, and that of P-selectin regionally, upregulated in the infarcted hearts when compared with nonischemic controls. Vascular adhesion protein-1 showed ventricular preponderance in expression and alterations in posttranslational modifications during ischemia-reperfusion. Importantly, P-selectin, ICAM-1 and VAP-1 mediated granulocyte binding to blood vessels in the ischemic human heart.</AbstractText>Human P-selectin, ICAM-1 and VAP-1 appear to be the most promising targets when antiadhesive interventions preventing leukocyte-mediated tissue destruction after myocardial ischemia are planned.</AbstractText> |
2,332,627 | Effect of renal denervation on renin gene expression, concentration, and secretion in mature ovine fetus. | To determine the role of the renal nerves on renin secretion and expression in the mature ovine fetus, we performed bilateral renal denervation on eight fetuses of time-dated pregnant ewes (126.8 +/- 0.6 days gestation) and compared renin in them to seven fetuses that underwent sham denervation (126.7 +/- 0.6 days gestation). Fetal arterial and venous catheters were implanted, and after 5-7 days of recovery isoproterenol was infused. Plasma active renin was lower in denervated animals than in intact animals under basal conditions and at each dose of isoproterenol. Plasma prorenin levels were lower in denervated fetuses but unaffected by isoproterenol. Denervation did not change renal renin, prorenin, or renin mRNA, but it did block isoproterenol-induced increases in renin mRNA in renocortical cells in vitro. We conclude that the renal nerves are required for renin secretory mechanisms and responsiveness of renin mRNA to beta-adrenergic stimulation but not for the expression of renin in the fetal kidney. We propose that one or more of the factors that maintain renin expression in the perinatal period may be absent or may be replaced by the renal nerves in the adult. |
2,332,628 | State-dependent barium block of wild-type and inactivation-deficient HERG channels in Xenopus oocytes. | The effects of Ba2+ on current resulting from the heterologous expression of the human ether-à-go-go related gene (HERG) (IHERG) was studied with two-electrode voltage clamp techniques in Xenopus oocytes. Ba2+ produced time- and voltage-dependent block of IHERG. Significant inhibition was seen at concentrations as low as 1 microM. Inhibition was greatest at step potentials between -40 and 0 mV; at more positive potentials, inhibition decreased in association with time-dependent unblocking of channels. An inactivation-attenuated mutant of HERG (S631A) was prepared and expressed in Xenopus oocytes. Ba2+ block of S631A differed from that of HERG in that extensive unblocking was no longer seen at positive potentials and the voltage dependence of step current block was greatly attenuated. A mathematical model was applied to analyse quantitatively the inhibitory effects of Ba2+ on IHERG. The model suggested similar voltage-dependent affinity of Ba2+ for the open and closed states, along with absence of binding to the inactivated state, and accounted well for Ba2+ effects on both wild-type and S631A channels. We conclude that Ba2+ potently inhibits IHERG in a characteristic state-dependent fashion, with strong unblocking at positive potentials related to the presence of an intact C-type inactivation mechanism. |
2,332,629 | Mechanism of suppression of cardiac L-type Ca(2+) currents by the phospholipase A(2) inhibitor mepacrine. | Phospholipase A(2) plays a crucial role in the release of arachidonic acid (AA) from membrane phospholipids and in myocardial injury during ischemia and reperfusion. Mepacrine, a phospholipase A(2) inhibitor, has been shown to protect the heart from ischemic injury. In order to examine the mechanism of this protection, we investigated the effects of mepacrine on the L-type Ca(2+) current (I(Ca,L)) in rat single ventricular myocytes. Extracellular application of mepacrine significantly inhibited I(Ca,L) in a tonic- and use-dependent manner. The inhibition was also concentration-dependent with an IC(50) of 5.2 microM. Neither the activation nor the steady-state inactivation of I(Ca,L) was altered by mepacrine. The mepacrine-induced inhibition of I(Ca,L) was reversible after washout of the inhibitor. Addition of 1 microM AA partially reversed the mepacrine-induced inhibition of I(Ca,L). Intracellular dialysis, with 2 mM cAMP, significantly increased I(Ca, L), but did not prevent the mepacrine-induced inhibition of I(Ca,L). In addition, extracellular application of isoproterenol or membrane permeable db-cAMP did not reverse the mepacrine-induced inhibition of I(Ca,L). Biochemical measurement revealed that incubation of ventricular myocytes with mepacrine significantly reduced intracellular cAMP levels. The mepacrine-induced reduction of cAMP production was abolished by addition of AA. Our results demonstrate that mepacrine strongly inhibits cardiac I(Ca,L). While mepacrine is a phospholipase A(2) inhibitor and reduces cAMP production, its inhibitory effect on I(Ca,L) mainly results from a direct block of the channel. Therefore, we speculate that the protective effect of mepacrine during myocardial ischemia and reperfusion mostly relates to its blockade of Ca(2+) channels. |
2,332,630 | Propofol dosage achieving spontaneous breathing during balanced regional anesthesia with the laryngeal mask airway. | To assess an anesthetic technique achieving spontaneous breathing through the laryngeal mask airway (LMA) during combined epidural block and propofol anesthesia.</AbstractText>Prospective, consecutive case series study.</AbstractText>Operating room at a general hospital.</AbstractText>112 ASA physical status I and II adult surgery patients; 32 patients for lower extremity surgery are enrolled into study 1, and 30 patients for lower extremity surgery and 50 patients for lower abdominal gynecology surgery are enrolled into study 2.</AbstractText>In study 1, patients were given 1.5 to 2.0 mg/kg followed by a 3 mg/kg/h of infusion of propofol, after epidural block, and they were fitted with the LMA. Thirty minutes after induction, the dose of propofol was increased to 4, 5, 6, and 7 mg/kg/h every 15 minutes. In study 2, the patients were given 1.5 to 2.0 mg/kg and 5 mg/kg/h of propofol and the LMA insertion, after epidural block.</AbstractText>PaO(2)/FIO(2), PaCO(2), tidal volume or respiratory rate, blood pressure, heart rate, and eye opening and motor response scales in conformity with Glasgow coma scale were recorded. Study 1 suggested an induction dose of 1.5 to 2.0 mg/kg and an infusion of 5 mg/kg/h as an appropriate dose to preserve spontaneous breathing with the LMA and to maintain reasonable depth of anesthesia. Study 2 showed that respiratory and circulatory conditions, depth of anesthesia, and other data related to anesthesia were clinically acceptable.</AbstractText>The best infusion dose of propofol to achieve spontaneous breathing with the LMA seems to be 5 mg/kg/h, and the present balanced regional anesthesia with the LMA, using propofol infusion at 1.5 to 2.0 mg/kg and 5 mg/kg/h combined with epidural block, may be useful in clinical practice for lower extremity and lower abdominal gynecologic operations.</AbstractText> |
2,332,631 | JTV-519, a novel cardioprotective agent, improves the contractile recovery after ischaemia-reperfusion in coronary perfused guinea-pig ventricular muscles. | A newly synthesized benzothiazepine derivative, JTV-519 (JT) has been reported to be cardioprotective. However, the precise mechanism underlying the cardioprotective effect of this drug is unknown. Coronary-perfused guinea-pig ventricular muscles were subjected to 20-min no-flow ischaemia followed by 60-min reperfusion (I/R). I/R significantly decreased the contraction in untreated preparations (control group, 34+/-4% of baseline value, n=6). Brief administration of JT (1.0 microM) prior to ischaemia significantly improved the postischaemic contractile recovery (63+/-5% of baseline value, n=4), as compared to the control group. JT (1.0 microM) slightly prolonged action potential duration before ischaemia and induced conduction disturbance (2 : 1 block) after the initiation of ischaemia. The cardioprotective effect of JT was antagonized by chelerythrine (CH, 5.0 microM), an inhibitor of protein kinase C (PKC) or by 5-hydroxydecanoic acid (5-HD, 400 microM), an inhibitor of mitochondrial ATP-sensitive K(+) (K(ATP)) channels. These results suggest that the protective effect of JT is due to the opening of mitochondrial K(ATP) channels, which, in turn, is linked to PKC activation. |
2,332,632 | Relationship between cortical electrical and cardiac autonomic activities in the awake lizard, Gallotia galloti. | ECG and EEG signals were simultaneously recorded in lizards, Gallotia galloti, both in control conditions and under autonomic nervous system (ANS) blockade, in order to evaluate possible relationships between the ANS control of heart rate and the integrated central nervous system activity in reptiles. The ANS blockers used were prazosin, propranolol, and atropine. Time-domain summary statistics were derived from the series of consecutive R-R intervals (RRI) of the ECG to measure beat-to-beat heart rate variability (HRV), and spectral analysis techniques were applied to the EEG activity to assess its frequency content. Both prazosin and atropine did not alter the power spectral density (PSD) of the EEG low frequency (LF: 0.5-7.5 Hz) and high frequency (HF: 7.6-30 Hz) bands, whereas propranolol decreased the PSD in these bands. These findings suggest that central beta-adrenergic receptor mechanisms could mediate the reptilian waking EEG activity without taking part any alpha(1)-adrenergic and/or cholinergic receptor systems. In 55% of the lizards in control conditions, and in approximately 43% of the lizards under prazosin and atropine, a negative correlation between the coefficient of variation of the series of RRI value (CV(RRI)) and the mean power frequency (MPF) of the EEG spectra was found, but not under propranolol. Consequently, the lizards' HRV-EEG-activity relationship appears to be independent of alpha(1)-adrenergic and cholinergic receptor systems and mediated by beta-adrenergic receptor mechanisms. |
2,332,633 | Effect of the dry-cold season dormancy on the tonic and phasic neural control of heart rate in the toad, Bufo paracnemis. | This work examined basal heart rate and autonomic cardiac tone as well as sympathetic cardiac reactivity to hypotension induced by systemic nitroprusside injection in dormant toads (dry-cold season), Bufo paracnemis, comparing the values with those of toads collected during the active months (hot-rainy season). Autonomic tone was calculated according to the method of Lin and Horwath ('72), which allows its evaluation as a percentage of intrinsic heart rate. Specimens were maintained in an outdoors terrarium except for the week preceding surgery, when they were transferred to indoor nonclimatized tanks. The heart rate of dormant toads (27.8 +/- 2.7 beats/min) was lower than that of active toads at rest (38.6 +/- 2. 3). Cholinergic tone was higher than adrenergic tone both in active (26.2% and 7.8%, respectively) and aestivated (19.5% and 4.8%, respectively) animals. Thus, cholinergic tone and adrenergic tone were both lower in dormant animals. The reflex tachycardia elicited by nitroprusside-induced hypotension was lower in aestivated toads (9.3 +/- 0.9 beats/min) when compared to active toads (19.9 +/- 1.0), indicating a reduced sympathetic reactivity. Nitroprusside-induced hypotensions were not different in the two groups. We conclude that at rest Bufo paracnemis heart is under the influence of a double cholinergic and adrenergic tone, and that both influences, as well as the reflex adrenergic reactivity to the unloading produced by nitroprusside-induced hypotension, are reduced in aestivated toads. |
2,332,634 | Late post-myocardial infarction induces a tetrodotoxin-resistant Na(+)Current in rat cardiomyocytes. | Left ventricular remodeling after myocardial infarction is accompanied by electrical abnormalities that might predispose to rhythm disturbances. To get insight into the ionic mechanisms involved, we studied myocytes isolated from four different regions of the rat ventricles, 4-6 months after ligation of the left coronary artery. Using the whole-cell patch-clamp technique, we never observed T-type Ca(2+)current in both diseased and control hearts. In contrast, in 41 out of 78 cells isolated from 16 post-myocardial infarcted rats, analysed in the presence of 30 m m Na(+)ions, we found a tetrodotoxin (TTX)-resistant Na(+)current with quite variable amplitude in every investigated region. Albeit being resistant to 100 microM TTX, this Na(+)-dependent current was highly sensitive to lidocaine since 3 microM lidocaine induced about 65% tonic block. It was also inhibited by 5 microM nifedipine and 2 m m Co(2+), but was insensitive to 100 microM Ni(2+). The TTX-resistant Na(+)channel availability was shifted rightward by 25-30 mV with respect to TTX-sensitive Na(+)current; therefore, a large "window current" might flow in the voltage range from -70 to -20 mV. In conclusion, in late post-myocardial infarction, a Na(+)current with specific kinetics and pharmacology may provide inward charges in a critical range of membrane voltages that are able to alter action potential time course and trigger ventricular arrhythmia. These apparent new characteristics of the Na(+)channel might result in part from environmental changes during heart remodeling. |
2,332,635 | Exogenous nitric oxide can trigger a preconditioned state through a free radical mechanism, but endogenous nitric oxide is not a trigger of classical ischemic preconditioning. | Nitric oxide (NO) has been reported to play an important role in the late phase of ischemic preconditioning (PC) in the rabbit heart. However, the role of NO in the early phase of ischemic PC ("classical PC") is controversial. Accordingly, the present study was designed to determine whether NO contributes to the cardioprotective effect of classical PC in rabbits. Isolated hearts experienced 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size was measured with triphenyltetrazolium chloride. In control hearts infarction was 30.2+/-3.3% of the risk zone. PC with 5 min of global ischemia and 10 min of reperfusion reduced infarct size to 10.2+/-2.4% (P<0.05). Perfusion with 2 microm S-nitroso-N-acetylpenicillamine (SNAP), a NO donor, in lieu of ischemia mimicked PC (4.4+/-1.9% infarction, P<0.01 v control). To determine whether this protection was dependent on either protein kinase C (PKC) as has previously been demonstrated for classical PC or free radicals known to be produced during exogenous NO administration, chelerythrine (5 microm), a PKC inhibitor, or N-(2-mercaptopropionyl)-glycine (300 microm), a free radical scavenger, was administered with or shortly after SNAP. Neither drug had any independent effect on infarct size, and each blocked SNAP's cardioprotection (31.0+/-5.1 and 25.7+/-5.2% infarction, resp.). N(omega)-nitro- L -arginine methyl ester (L -NAME, 100 microm), a NO synthase inhibitor, failed to block the cardioprotection from the above ischemic PC protocol (9.5+/-2.8% infarction, P<0.05 v control). L -NAME alone had no effect on infarct size (30.6+/-2.7%). These results suggest that the beneficial effect of exogenous NO production during SNAP pretreatment is mediated by a protein kinase C-dependent pathway via MPG-sensitive oxidants. However, we were unable to show any contribution of endogenous NO to classical PC's protection in isolated rabbit hearts. |
2,332,636 | The effect of acute hyperglycaemia on QTc duration in healthy man. | <AbstractText Label="AIMS/HYPOTHESIS" NlmCategory="OBJECTIVE">Prolongation of heart rate-adjusted QT (QTc) is associated with an increased risk of coronary heart disease and sudden death. The objective of this study was to investigate whether acute increases of plasma glucose concentrations in healthy subjects could influence QTc and QTc dispersion.</AbstractText>Plasma glucose concentrations were quickly raised to 15 mmol/l in 20 healthy subjects (10 men/10 women) and maintained for 2 h. On another occasion, and in random order, all subjects underwent the same hyperglycaemic clamp as above and an infusion of the somatostatin analogue octreotide (25 microg as iv bolus followed by a 0.5 g/min infusion) to block the release of endogenous insulin.</AbstractText>Systolic and diastolic blood pressures, heart rate and plasma catecholamine concentrations showed significant increases (p < 0.05) starting after 60 min of hyperglycaemia. QTc, QTc dispersion and PR interval also showed significant increments at 120 min of the hyperglycaemic clamp. The infusion of octreotide did not influence QTc duration, QTc dispersion, PR interval and the haemodynamic effects of acute hyperglycaemia.</AbstractText><AbstractText Label="CONCLUSION/INTERPRETATION" NlmCategory="CONCLUSIONS">The results show that acute hyperglycaemia produces significant increments of QTc and QTc dispersion in normal subjects. In this context, endogenously released insulin during acute hyperglycaemia seems to play a minor part.</AbstractText> |
2,332,637 | Effects of humanized monoclonal antibody to rhesus CD11a in rhesus monkey cardiac allograft recipients. | Leukocyte function-associated antigen-1 (LFA-1, CD11a) monoclonal antibody (mAb) affects many leukocyte functions without cell depletion. We hypothesized that the use of a humanized, anti-rhesus modified LFA-1 mAb (H2C12) in rhesus monkeys would cause: (1) prolonged heart allograft survival, (2) inhibition of primary but not secondary antibody responses, and (3) minimal drug toxicity.</AbstractText>Control (n=5) and H2C12-treated (n=7) (8-20 mg/kg i.v. on day -1 followed by 10 mg/kg/day) adult male rhesus recipients were inoculated with GP120 protein antigen on day -28 and -1 and grafted with heterotopic abdominal hearts (day 0). Donor-recipient pairs were equally MLR mismatched (4329.8+/-1124.1 CPM controls vs. 7289.0+/-1926.5 treated, P=NS). Mean heart allograft survival as evaluated by daily abdominal palpation was significantly prolonged in high dose recipients (23.0+/-2.6, n=4) vesus controls (8.2+/-1.3, n=5, P<0.02, Mann-Whitney U test). H2C12 treatment did not produce signs of cytokine release or toxicity, was nondepleting, but down-modulated PBL CD11a expression to 43.4+/-3.6% (n=4) of control levels (n=5) at day 7 as demonstrated by flow cytometry. It had no effect on postoperative Con A or MLR and did not prevent mAb clearance due to the rhesus-antihuman antibody response. The addition of mycophenolate mofitil prevented rhesus-antihuman antibody response with therapeutic H2C12 levels seen for >35 days.</AbstractText>The use of this mAb to block CD11a had the benefit of being a well tolerated, highly targeted therapy. These are the first results showing that monotherapy with anti-leukocyte function-associated antigen-1 mAb prolonged survival of MLR mismatched allogenic cardiac grafts in primates.</AbstractText> |
2,332,638 | Changes in catecholaminergic pathways innervating the rat heart ventricle during morphine dependence. Involvement Of alpha(1)- and alpha(2)-adrenoceptors. | In the present study, we examined the effects of alpha(1)- and the alpha(2)-adrenoceptors blockade on the changes in the ventricular content of catecholamines in rats withdrawn from morphine. Rats were given morphine by s.c. implantation of morphine pellets for 5 days. On the seventh day, morphine withdrawal was induced by s.c. administration of naloxone (1 mg/kg), and rats were killed 30 min later. Pretreatment with yohimbine (alpha(2)-adrenoceptor) or prazosin (alpha(1)-adrenoceptor) 15 min prior to naloxone administration attenuated some of the behavioural signs of morphine withdrawal. In addition, biochemical analysis indicated that yohimbine completely abolished the withdrawal-induced increase in noradrenaline and dopamine turnover in the right ventricle. By contrast, prazosin did not block the hyperactivity of catecholaminergic neurons in the heart during withdrawal. These data suggest that the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal is dependent upon alpha(2)-adrenoceptor activation. In addition, the present results rule out the involvement of alpha(1)-adrenoceptors. |
2,332,639 | Post-junctional mechanisms involved in the potentiation of cardiac adrenergic responses by cocaine. | Cocaine cardiotoxicity is partly due to sympathetic activation of the heart resulting from inhibition of catecholamine uptake at the sympathetic nerve terminal and possible central sympathetic stimulation and/or inhibition. This study evaluated the role of postsynaptic mechanisms in potentiation by cocaine of cardiac adrenergic responses. Cardiovascular responses (arterial and left ventricular pressure, contractility and heart rate) to increasing doses of noradrenaline and to isoproterenol were obtained in anesthetized cats during a control period, after irreversible alpha-adrenoceptor blockade with phenoxybenzamine (5 mg/kg i.v.), and after cocaine (5 mg/kg, i.v.). Responses to noradrenaline were significantly reduced by phenoxybenzamine with lowering of the maximal rise of all parameters. Cocaine shifted the dose-response curve of noradrenaline to the left and enhanced its maximal effects. Some responses to isoproterenol, which is not taken up by nerve terminals, were also enhanced by cocaine. Pretreatment with chlorisondamine or verapamil prevented the cocaine-induced enhancement of the maximal response to noradrenaline and the response to isoproterenol, but it did not inhibit potentiation of submaximal doses. Lidocaine did not potentiate the response to noradrenaline or isoproterenol. Use of chlorisondamine instead of cocaine potentiated responses to all noradrenaline doses and enhanced the responses to isoproterenol. These results suggest that the potentiation by cocaine of cardiac responses to adrenergic stimuli involves presynaptic mechanisms to block noradrenaline re-uptake, and postsynaptic mechanisms to raise the maximal responses. The latter may result from inhibition of central sympathetic outflow or from activation of cardiac Ca(+) channels, leading to increased cardiac sensitivity to noradrenaline. |
2,332,640 | Endogenous tachykinins cause bradycardia by stimulating cholinergic neurons in the isolated guinea pig heart. | The purpose of this study was to determine if endogenous tachykinins can cause bradycardia in the isolated perfused guinea pig heart through stimulation of cholinergic neurons. Capsaicin was used to stimulate release of tachykinins and calcitonin gene-related peptide (CGRP) from cardiac afferents. A bolus injection of 100 nmol capsaicin increased heart rate by 26 +/- 7% from a baseline of 257 +/- 14 beats/min (n = 6, P < 0.01). This positive chronotropic response was converted to a minor bradycardic effect in hearts with 1 microM CGRP-(8-37) present to block CGRP receptors. The negative chronotropic response to capsaicin was markedly potentiated in another group of hearts with the further addition of 0.5 microM neostigmine to inhibit cholinesterases. In this group, capsaicin decreased heart rate by 30 +/- 10% from a baseline of 214 +/- 6 beats/min (n = 8, P < 0.05). This large bradycardic response to capsaicin was inhibited by 1) infusion of neurokinin A to desensitize tachykinin receptors or 2) treatment with 1 microM atropine to block muscarinic receptors. The latter observations implicate tachykinins and acetylcholine, respectively, as mediators of the bradycardia. These findings support the hypothesis that endogenous tachykinins could mediate axon reflexes to stimulate cholinergic neurons of the intrinsic cardiac ganglia. |
2,332,641 | TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II. | The present study was conducted to explore the possible contribution of a recently described leak K+ channel, TASK (TWIK-related acid-sensitive K+ channel), to the high resting K+ conductance of adrenal glomerulosa cells. Northern blot analysis showed the strongest TASK message in adrenal glomerulosa (capsular) tissue among the examined tissues including heart and brain. Single-cell PCR demonstrated TASK expression in glomerulosa cells. In patch-clamp experiments performed on isolated glomerulosa cells the inward current at -100 mV in 30 mM [K+] (reflecting mainly potassium conductance) was pH sensitive (17+/-2% reduction when the pH changed from 7.4 to 6.7). In Xenopus oocytes injected with mRNA prepared from adrenal glomerulosa tissue the expressed K+ current at -100 mV was virtually insensitive to tetraethylammonium (3 mM) and 4-aminopyridine (3 mM). Ba2+ (300 microM) and Cs+ (3 mM) induced voltage-dependent block. Lidocaine (1 mM) and extracellular acidification from pH 7.5 to 6.7 inhibited the current (by 28% and 16%, respectively). This inhibitory profile is similar (although it is not identical) to that of TASK expressed by injecting its cRNA. In oocytes injected with adrenal glomerulosa mRNA, TASK antisense oligonucleotide reduced significantly the expression of K+ current at -100 mV, while the sense oligonucleotide failed to have inhibitory effect. Application of angiotensin II (10 nM) both in isolated glomerulosa cells and in oocytes injected with adrenal glomerulosa mRNA inhibited the K+ current at -100 mV. Similarly, in oocytes coexpressing TASK and ATla angiotensin II receptor, angiotensin II inhibited the TASK current. These data together indicate that TASK contributes to the generation of high resting potassium permeability of glomerulosa cells, and this background K+ channel may be a target of hormonal regulation. |
2,332,642 | [Study of presurgical anxiety in urologic, gynecologic, and ophthalmologic surgery as a function of the administration or non-administration of anxiolytic premedication]. | Anxiety commonly appears before surgery, triggering a set of events that can be described as a general stress response. We measured changes in preoperative stress in relation to premedication or not with diazepam in patients undergoing urologic, gynecologic and ophthalmologic surgery.</AbstractText>We enrolled 87 patients undergoing elective surgery in urology (n = 30), gynecology (n = 30) and ophthalmology (n = 27). Randomly, the patients were premedicated with diazepam, placebo or nothing. During the preoperative visit the patient was administered a test to determine the level of anxiety and blood pressure, heart rate and potassium plasma concentration (K+) the night before surgery and moments before entering the operating theater.</AbstractText>No significant differences in anxiety between patients undergoing different types of surgery were detected in the operating theater; however, at that time, anxiety was found to be significantly less among patients premedicated with diazepam than among those given placebo. Preoperative anxiety was significantly less in ophthalmology patients and in those premedicated with diazepam. Both systolic and diastolic blood pressure increased significantly among urologic and ophthalmologic surgery patients and in those who were not premedicated with diazepam regardless of type of surgery. Heart rate did not change significantly. Potassemia decreased significantly in all patients.</AbstractText>The discrepancy between the psychological and somatic response to the stress conditions studied may be the result of the calming effect of the preoperative visit by the anesthesiologist and to premedication with a tranquilizer. However, neither the preoperative visit nor premedication seem to completely block the stress response.</AbstractText> |
2,332,643 | Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. | Hyperphosphatemia is a predictable consequence of chronic renal failure and is present in most patients on dialysis. Traditionally, the risk associated with elevated serum phosphorus has focused on its impact on renal osteodystrophy. A growing body of evidence, however, suggests that abnormalities in serum phosphorus, calcium-phosphorus product (CaxP), and parathyroid hormone (PTH) levels are resulting in vascular and visceral calcification, thereby contributing to the substantially increased risk of cardiovascular death in this population. In this analysis, we review in detail the literature that describes these associations. We show that the current treatment paradigm for serum phosphorus and secondary hyperparathyroidism is ineffective for a large segment of dialysis patients. Currently, 60% of hemodialysis patients have phosphorus greater than 5.5 mg/dL, and 40% have CaxP greater than 60 mg(2)/dL(2). It is our belief that prevention of uremic calcification, cardiac death, and vascular disease should assume primary importance when evaluating the risks associated with elevated levels of phosphorus, CaxP, and PTH. We recommend that target levels should become 9.2 to 9.6 mg/dL for calcium, 2.5 to 5.5 mg/dL for phosphorus, less than 55 mg(2)/dL(2) for CaxP product, and 100 to 200 pg/mL for intact PTH. |
2,332,644 | G protein-mediated FMRFamidergic modulation of calcium influx in dissociated heart muscle cells from squid, Loligo forbesii. | The actions of the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) on the L-type (ICa,L) and T-type (ICa,T) calcium currents were investigated in muscle cells dissociated from the heart of squid, Loligo forbseii. The heart muscle cells could be divided into type I and type II cells, on the basis of morphological differences in the dissociated myocytes. FMRFamide induced a substantial block of the L-type calcium current seen in type I cells; this inhibition was rapid, reversible and dose dependent (IC50 = 0.1 microM). FMRFamide induced an increase in the amplitude of the L-type calcium current in the type II heart muscle cells, but had no effect on the T-type calcium current in either type of dissociated heart muscle cell, even at concentrations much higher than those found to affect the L-type calcium current. Internal dialysis of isolated type I heart muscle cells with guanosine 5'-O-(3-thiotriphosphate (GTPgammaS, 100 microM), a non-hydrolysable GTP analogue, mimicked the FMRFamide inhibition of the Ca2+ current and occluded any further FMRFamide-induced inhibition. Internal dialysis of these cells with guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS, 100 microM) reduced the FMRFamide-induced inhibition of the peak Ca2+ current. The inhibitory effects of FMRFamide were abolished by pre-incubation of the cells with pertussis toxin (200 ng ml-1). The activation kinetics of ICa,L were not affected by FMRFamide application, nor by internal perfusion with GTPgammaS, and the FMRFamide-induced reduction in ICa,L was not relieved by large depolarising prepulses. These data indicate that FMRFamide can modulate ICa,L, but not ICa,T, in squid heart muscle cells, and that the underlying G protein pathway is dissimilar to that commonly associated with transmitter modulation of channel activity. The FMRFamide-modulated increase in ICa,L seen in the type II heart muscle cells was not mediated by a PTX-sensitive G protein pathway. |
2,332,645 | Fetal oxygen saturation during epidural and paracervical analgesia. | We wanted to assess changes in fetal oxygenation during maternal epidural or paracervical analgesia in labor.</AbstractText>A prospective, open and non-randomized study. Twenty healthy parturients were enrolled before they asked for pain relief. Informed consent was obtained. Fetal and maternal oxygen saturations were measured before and up to 1 h after the initiation of analgesia. Fetal oximetry was performed with the Nellcor N-400 oximeter+FS-14B fetal oxygen sensor (Nellcor Puritan Bennett, Pleasanton, California, USA). Maternal oximetry was done with Datex Satlite portable monitor (Datex, Finland). Visual analog scale was used for assessing pain relief. Two-way analysis of variance and students t-test were used for statistical analyses.</AbstractText>Fetal oxygenation initially improved in both groups. The saturation then returned to baseline in both groups. In the epidural group, the values remained at baseline or slightly below, while in the paracervical group the saturation remained a little higher than baseline (p=0.009). No change was seen in maternal oxygenation or heart rate. No change in fetal heart rate was found either. Epidural block was superior to paracervical block with respect to pain relief (p=0.002).</AbstractText>There was a small but significant difference in fetal oxygenation between epidural and paracervical groups during the observation period. The magnitude of the difference is hardly clinically significant. A larger, randomized study is needed to elucidate the mechanisms behind this finding.</AbstractText> |
2,332,646 | Isoproterenol and cAMP regulation of the human brain natriuretic peptide gene involves Src and Rac. | Brain natriuretic peptide (BNP) gene expression and chronic activation of the sympathetic nervous system are characteristics of the development of heart failure. We studied the role of the beta-adrenergic signaling pathway in regulation of the human BNP (hBNP) promoter. An hBNP promoter (-1818 to +100) coupled to a luciferase reporter gene was transferred into neonatal cardiac myocytes, and luciferase activity was measured as an index of promoter activity. Isoproterenol (ISO), forskolin, and cAMP stimulated the promoter, and the beta(2)-antagonist ICI 118,551 abrogated the effect of ISO. In contrast, the protein kinase A (PKA) inhibitor H-89 failed to block the action of cAMP and ISO. Pertussis toxin (PT), which inactivates Galpha(i), inhibited ISO- and cAMP-stimulated hBNP promoter activity. The Src tyrosine kinase inhibitor PP1 and a dominant-negative mutant of the small G protein Rac also abolished the effect of ISO and cAMP. Finally, we studied the involvement of M-CAT-like binding sites in basal and inducible regulation of the hBNP promoter. Mutation of these elements decreased basal and cAMP-induced activity. These data suggest that beta-adrenergic regulation of hBNP is PKA independent, involves a Galpha(i)-activated pathway, and targets regulatory elements in the proximal BNP promoter. |
2,332,647 | Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. | Channels formed by coassembly of the KCNQ1 (KvLQT1) subunit and the minK subunit underlie slowly activating cardiac delayed rectifier (I(Ks)) in the heart, whereas two other members of the KCNQ channel family, KCNQ2 and KCNQ3, coassemble to underlie the M current in the nervous system. Because of their important physiological function, KCNQ channels have potential as drug targets, and an understanding of possible mechanisms that would enable tissue-specific targeting of these channels will be of significant value to drug development. In this study, we examined the role of the minK subunit in determining the response of KCNQ1 channels to blockade by the cognitive enhancer XE991. Coexpression with minK markedly decreased the sensitivity of KCNQ1 to blockade by XE991. When measured at the end of a 500-ms step, XE991 blockade of the KCNQ1+minK current had a K(D) value of 11.1 +/- 1.8 microM, approximately 14-fold less sensitive than the block of the KCNQ1 current (K(D) = 0.78 +/- 0.05 microM). In addition, XE991 reduced activation and deactivation time constants and caused a rightward shift in the activation curve of KCNQ1+minK, but affected none of these parameters for KCNQ1 alone. Also, XE991 block of KCNQ1+minK, but not of KCNQ1, was time- and voltage-dependent. We conclude that the presence of minK in the I(Ks) channel complex gives rise to differential sensitivity of KCNQ and I(Ks) channels to blockade by XE991. Our results have implications for drug development by demonstrating the important potential role of accessory subunits in determining the pharmacological properties of KCNQ channels. |
2,332,648 | In vivo beta3-adrenergic stimulation of human thermogenesis and lipid use. | To investigate the role of the human beta3-adrenergic receptor in in vivo isoproterenol (INN, isoprenaline)-induced thermogenesis and lipid use.</AbstractText>Eight male volunteers participated in two studies. In the first study subjects received oral dosages of 2.5, 7.5, 15, and 40 mg nadolol or propranolol (both beta1- and beta2-adrenergic receptor antagonists) at random, after which isoproterenol (beta1-, beta2-, and beta3-adrenergic receptor agonist) was infused in an individually determined dosage (range, 19 to 35 ng/kg x min) that increased energy expenditure by 25% without pretreatment. In the second study, 50, 100, and 200 ng/kg x min isoproterenol or saline solution were infused after pretreatment with 80 mg nadolol. In both studies energy expenditure and respiratory exchange ratio were measured by indirect calorimetry and, at the end of each infusion period, blood samples were taken and tremor score (only first study), heart rate, and blood pressure were measured.</AbstractText>In the first study, nadolol or propranolol in doses < or =40 mg could not fully block beta1-adrenergic receptor-mediated increases in heart rate and systolic blood pressure. Propranolol in doses < or =7.5 mg could not fully block the beta2-adrenergic receptor-mediated increase in tremor score during isoproterenol infusion. The increases found in thermogenesis and lipid use could therefore be explained by concomitant beta1- and beta2-adrenergic stimulation. In the second study, isoproterenol infusion induced a significant increase in heart rate, but no increases in thermogenesis and lipid use were found compared with infusion of saline solution.</AbstractText>No evidence could be found for a beta3-adrenergic receptor-mediated increase in human thermogenesis and lipid use during isoproterenol infusion after pretreatment with nadolol or propranolol.</AbstractText> |
2,332,649 | Gene transfer of virally encoded chemokine antagonists vMIP-II and MC148 prolongs cardiac allograft survival and inhibits donor-specific immunity. | Introducing immunomodulatory molecules into allografts by gene transfer may avoid the side-effects of systemic immunosuppression. vMIP-II and MC148 are two recently identified chemokine homologues encoded by human herpes virus 8 and Molluscum contagiosum, respectively, that have antagonistic activities against multiple different CC and CXC chemokine receptors. We hypothesized that introduction of these molecules into cardiac allografts may block leukocyte infiltration into the grafts and prolong survival. Vascularized and nonvascularized cardiac allografts in mice were performed and plasmid DNA encoding vMIP-II, MC148 and/or vIL-10 was transferred into the allograft at the time of transplantation. Gene transfer of either vMIP-II or MC148 into cardiac allografts markedly prolonged graft survival. Combining gene transfer of either one of these chemokine antagonists with vIL-10 gene transfer, which has a mechanistically different immunosuppressive action, further enhanced graft survival. vMIP-II and MC148 gene transfer both resulted in a marked decrease of donor-specific cytotoxic T lymphocytes (CTL) infiltrating the grafts and inhibited alloantibody production. These results demonstrate that plasmid-mediated gene transfer of virally encoded chemokine antagonists vMIP-II and MC148 can block donor-specific lymphocyte immunity within cardiac allografts and prolong graft survival. This is a new mechanistic approach to analyze, treat, and prevent graft rejection. Delivery of these or related molecules by gene transfer or conventional pharmacologic means may represent a novel therapeutic modality for alloactivation. |
2,332,650 | Severe bradycardia and bradypnea following vaginal oocyte retrieval: a possible toxic effect of paracervical mepivacaine. | We report a case of a patient with a history of heart conduction disease, symptom-free and without treatment in the last years, who experienced a severe cardiac complication associated with in vitro fertilization (IVF) with vaginal oocyte retrieval (VOR). Eighty-five minutes after the VOR a severe bradycardia and bradypnea occurred, requiring an emergency application of a pacemaker. Presumably the condition occurred because of a toxic effect of the 400 mg of mepivacaine administered paracervically. It is concluded that in the paracervical anesthesia in the IVF cycles the therapeutic range should be scrupulously followed in patients with heart condition. |
2,332,651 | QT interval prolongation in asymptomatic anti-SSA/Ro-positive infants without congenital heart block. | To analyze the electrocardiograms (EKGs) of infants born to mothers with anti-SSA/Ro antibodies in order to evaluate the QT interval (the time from the beginning of the QRS complex to the end of the T wave).</AbstractText>Sera from mothers and children were analyzed for anti-Ro and anti-SSB/La antibodies by enzyme-linked immunosorbent assay (ELISA) and by Western blot analysis. Fine specificity of anti-Ro antibodies was evaluated by solid-phase ELISA against recombinant 52- and 60-kd proteins and by Western blot. A retrospective chart review was conducted for EKG analysis. Twenty-eight EKG tracings (21 from anti-Ro-positive and 7 from anti-Ro-negative infants born to mothers with autoimmune diseases) were analyzed by a single investigator who was blinded to the infant's antibody status. The QT interval was measured and corrected for heart rate according to Bazett's formula.</AbstractText>The mean QT interval was significantly longer in anti-Ro-positive than in anti-Ro-negative infants, also after correction for heart rate (QTc) (P = 0.001). Nine of 21 anti-Ro-positive infants and 0 of 7 anti-Ro-negative infants had QTc values above the upper normal limit (440 msec). A 24-hour EKG recording was performed on 5 patients and confirmed the QT prolongation. These infants were subsequently treated with a beta-blocker in order to prevent arrhythmias.</AbstractText>Infants born to mothers who carry anti-Ro autoantibodies may show QT interval prolongation and should be monitored with EKG during the first months of life.</AbstractText> |
2,332,652 | alpha B-crystallin gene induction and phosphorylation by MKK6-activated p38. A potential role for alpha B-crystallin as a target of the p38 branch of the cardiac stress response. | The MAPK kinase MKK6 selectively stimulates p38 MAPK and confers protection against stress-induced apoptosis in cardiac myocytes. However, the events lying downstream of p38 that mediate this protection are unknown. The small heat shock protein, alphaB-crystallin, which is expressed in only a few cell types, including cardiac myocytes, may participate in MKK6-mediated cytoprotection. In the present study, we showed that, in cultured cardiac myocytes, expression of MKK6(Glu), an active form of MKK6, led to p38-dependent increases in alphaB-crystallin mRNA, protein, and transcription. MKK6(Glu) also induced p38-dependent activation of the downstream MAPK-activated protein kinase, MAPKAP-K2, and the phosphorylation of alphaB-crystallin on serine-59. Initially, exposure of cells to the hyperosmotic stressor, sorbitol, stimulated MKK6, p38, and MAPKAP-K2 and increased phosphorylation of alphaB-crystallin on serine 59. However, after longer times of exposure to sorbitol, the cells began to undergo apoptosis. This sorbitol-induced apoptosis was increased when p38 was inhibited in a manner that would block alphaB-crystallin induction and phosphorylation. Thus, under these conditions, the activation of MKK6, p38, and MAPKAP-K2 by sorbitol can provide a degree of protection against stress-induced apoptosis. Supporting this view was the finding that sorbitol-induced apoptosis was nearly completely blocked in cells expressing MKK6(Glu). Therefore, the cytoprotective effects of MKK6 in cardiac myocytes are due, in part, to phosphorylation of alphaB-crystallin on serine 59 and to the induction of alphaB-crystallin gene expression. |
2,332,653 | Naltrexone does not block the subjective effects of oral Delta(9)-tetrahydrocannabinol in humans. | Delta(9)-tetrahydrocannabinol (THC) and opioids have many common effects. In addition, some THC effects in laboratory animals can be blocked or attenuated by opioid antagonists. This suggests that opioid systems mediate or modulate some THC effects. To determine whether opioid systems mediate THC effects in humans, the effects of the opioid antagonist naltrexone on subjective responses to THC were examined in 14 marijuana users. Subjects participated in a double-blinded, cross-over design in which each subject received all combinations of naltrexone (0 or 50 mg) and THC (0, 7.5, or 15 mg). THC increased heart rate and self-reported drug effects, such as euphoria and marijuana-like effects, and decreased psychomotor performance. Naltrexone increased heart rate and decreased self-reported measures of vigor and hunger but did not alter any of the effects of THC. These results suggest that the subjective, physiological, and behavioral effects of THC in humans are not mediated through opioid systems. |
2,332,654 | Immune responses to SS-A 52-kDa and 60-kDa proteins and to SS-B 50-kDa protein in mothers of infants with neonatal lupus erythematosus. | Mothers who have anti-SS-A/Ro and anti-SS-B/La antibodies have a greater risk of bearing infants with neonatal lupus erythematosus (NLE). However, most mothers with anti-SS-A/Ro and anti-SS-B/La antibodies give birth to infants with no evidence of NLE. We studied mothers who had the combination of clinical evidence of connective tissue disorder, positive antinuclear antibody and positive anti-SS-A/Ro and/or anti-SS-B/La antibodies. We analysed SS-A/Ro and SS-B/La antibody responses to recombinant 60-, 52- and 50-kDa proteins in eight mothers of NLE infants and 19 mothers whose children did not have NLE. Molecular analysis of the anti-SS-A/Ro and anti-SS-B/La antibodies was carried out by enzyme-linked immunosorbent assay using recombinant 60-, 52- and 50-kDa proteins. The mothers of children with cutaneous NLE were all positive for a high titre of 50-kDa protein. Mothers of children with NLE with complete heart block (CHB) were positive for 52- and 60-kDa proteins. We conjecture that anti-SS-B/La antibody influences the development of cutaneous NLE, and that anti-SS-A/Ro antibody influences the development of NLE with CHB. |
2,332,655 | Central control of cardiac baroreflex responses during peripheral hyperosmolality. | Acute increases in peripheral osmolality evoke a pressor response and baroreflex-mediated bradycardia. These experiments were designed to determine if the fall in heart rate during peripheral sodium loading is 1) equivalent to bradycardia accompanying phenylephrine (PE) infusion, 2) mediated by the parasympathetic (PSNS) or sympathetic (SNS) nervous system, and 3) controlled by the median preoptic nucleus (MnPO). Male rats received an intravenous infusion of isotonic saline, hypertonic saline (2.5 M NaCl), or PE for 30 min. Blood pressure increased equivalently in the hypertonic NaCl and PE groups. However, heart rate fell more in animals infused with PE. Furthermore, pretreatment with methylatropine to block the PSNS had no effect on bradycardia, whereas blocking SNS influences on cardiac function significantly attenuated the fall in heart rate during peripheral hyperosmolality. Finally, kainic acid administration in the MnPO before testing increased bradycardia observed during hypertonic saline loading. Taken together, these data suggest that acute peripheral hyperosmolality acts at the MnPO to reduce cardiac SNS withdrawal during the pressor response that reduces the associated baroreflex bradycardia. |
2,332,656 | [Chronic cardiac insufficiency. Treatment with angiotensin I converting enzyme inhibitors and angiotensin II receptor antagonists].<Pagination><StartPage>743</StartPage><EndPage>748</EndPage><MedlinePgn>743-8</MedlinePgn></Pagination><Abstract><AbstractText>RENIN-ANGIOTENSIN SYSTEM: This system plays a major role in regulation of blood pressure. Angiotensin converting enzyme inhibitors (CEI) modify the balance between the vasocilator and diuretic properties of bradykinin and the vasoconstrictor and antidiuretic properties of angiotensin II, favoring vasodilatation and natriuresis. Angiotensin II receptor antagonists (ARAII) block AT1 receptors and stimulate AT2 receptors with favorable vasodilator and natriuretic affects. CEI: Converting enzyme inhibitors play an indispensable role in the treatment of heart failure and should be prescribed at high dosage. They have a long-term beneficial effect. ARAII: These compound could play a role in the future, but studies conducted to date comparing ARAII and CEI have been unable to demonstrate superior or equivalent effects with ARAII, and do not warrant their prescription for hypertension.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Juilliére</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>CHU Nancy-Brabois, Vandoeuvre-les-Nancy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Berder</LastName><ForeName>V</ForeName><Initials>V</Initials></Author></AuthorList><Language>fre</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Insuffisance cardiaque chronique. Traitement par les inhibiteurs de l'enzyme de conversion de l'angiotensine I et les antagonistes des récepteurs à l'angiotensine II.</VernacularTitle></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Presse Med</MedlineTA><NlmUniqueID>8302490</NlmUniqueID><ISSNLinking>0755-4982</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057911">Angiotensin Receptor Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000806">Angiotensin-Converting Enzyme Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>11128-99-7</RegistryNumber><NameOfSubstance UI="D000804">Angiotensin II</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000804" MajorTopicYN="N">Angiotensin II</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D057911" MajorTopicYN="Y">Angiotensin Receptor Antagonists</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000806" MajorTopicYN="N">Angiotensin-Converting Enzyme Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002303" MajorTopicYN="N">Cardiac Output, Low</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006333" MajorTopicYN="N">Heart Failure</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>5</Month><Day>8</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2000</Year><Month>6</Month><Day>8</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>5</Month><Day>8</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10797830</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10796371</PMID><DateCompleted><Year>2000</Year><Month>07</Month><Day>06</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>2</Issue><PubDate><Year>2000</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal>Lidocaine-prilocaine cream for analgesia during circumcision in newborn boys. | RENIN-ANGIOTENSIN SYSTEM: This system plays a major role in regulation of blood pressure. Angiotensin converting enzyme inhibitors (CEI) modify the balance between the vasocilator and diuretic properties of bradykinin and the vasoconstrictor and antidiuretic properties of angiotensin II, favoring vasodilatation and natriuresis. Angiotensin II receptor antagonists (ARAII) block AT1 receptors and stimulate AT2 receptors with favorable vasodilator and natriuretic affects. CEI: Converting enzyme inhibitors play an indispensable role in the treatment of heart failure and should be prescribed at high dosage. They have a long-term beneficial effect. ARAII: These compound could play a role in the future, but studies conducted to date comparing ARAII and CEI have been unable to demonstrate superior or equivalent effects with ARAII, and do not warrant their prescription for hypertension.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Juilliére</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>CHU Nancy-Brabois, Vandoeuvre-les-Nancy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Berder</LastName><ForeName>V</ForeName><Initials>V</Initials></Author></AuthorList><Language>fre</Language><PublicationTypeList><PublicationType UI="D004740">English Abstract</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Insuffisance cardiaque chronique. Traitement par les inhibiteurs de l'enzyme de conversion de l'angiotensine I et les antagonistes des récepteurs à l'angiotensine II.</VernacularTitle></Article><MedlineJournalInfo><Country>France</Country><MedlineTA>Presse Med</MedlineTA><NlmUniqueID>8302490</NlmUniqueID><ISSNLinking>0755-4982</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D057911">Angiotensin Receptor Antagonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000806">Angiotensin-Converting Enzyme Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>11128-99-7</RegistryNumber><NameOfSubstance UI="D000804">Angiotensin II</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000804" MajorTopicYN="N">Angiotensin II</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D057911" MajorTopicYN="Y">Angiotensin Receptor Antagonists</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000806" MajorTopicYN="N">Angiotensin-Converting Enzyme Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002303" MajorTopicYN="N">Cardiac Output, Low</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006333" MajorTopicYN="N">Heart Failure</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>5</Month><Day>8</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2000</Year><Month>6</Month><Day>8</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>5</Month><Day>8</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10797830</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10796371</PMID><DateCompleted><Year>2000</Year><Month>07</Month><Day>06</Day></DateCompleted><DateRevised><Year>2018</Year><Month>12</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>2</Issue><PubDate><Year>2000</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal><ArticleTitle>Lidocaine-prilocaine cream for analgesia during circumcision in newborn boys.</ArticleTitle><Pagination><StartPage>CD000496</StartPage><MedlinePgn>CD000496</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Neonates routinely undergo tissue-damaging interventions as part of medical treatment. The skin is the site of noxious stimulation for many procedures, including circumcision. EMLA (eutectic mixture of local anesthetics) penetrates intact skin and has the potential to reduce pain associated with circumcision.<AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To determine the effectiveness of EMLA compared to placebo or no treatment as an analgesic for circumcision in male newborns.<AbstractText Label="SEARCH STRATEGY" NlmCategory="METHODS">The guidelines of the Cochrane Neonatal Review Group were followed. No language restrictions were applied. Three reviewers (AT, KO, AO) agreed through a consensus process on the inclusion of a specific study.<AbstractText Label="SELECTION CRITERIA" NlmCategory="METHODS">Randomized controlled trials assessing the efficacy/effectiveness of EMLA to prevent circumcision associated pain. Behavioral and physiological outcome data were accepted for efficacy/effectiveness.<AbstractText Label="DATA COLLECTION AND ANALYSIS" NlmCategory="METHODS">Data abstracted from each report included gestational age at birth, timing and dosage regimen of EMLA, control group treatment and outcomes. Abstracted data were verified by the three investigators (AT, KO, AO).<AbstractText Label="MAIN RESULTS" NlmCategory="RESULTS">During the different stages of the surgical procedure for circumcision, the increase in heart rate was 12 - 27 beats per minute less for the EMLA group compared to placebo. In a single study, neonates treated with EMLA showed a higher oxygen saturation. Although the data from the three studies could not be combined, crying during circumcision was reported as less in the EMLA treated groups. In two studies, facial action was lower in the EMLA treated groups compared to placebo.<AbstractText Label="REVIEWER'S CONCLUSIONS" NlmCategory="CONCLUSIONS">EMLA reduces pain response during circumcision in newborn male infants. Other potentially more effective forms of analgesia for circumcision (such as dorsal penile nerve block, ring block) should be subjected to systematic reviews. |
2,332,657 | Digestive motor effects and vascular actions of CGRP in dog are expressed by different receptor subtypes. | Calcitonin gene-related peptide (CGRP) is a 37 AA peptide localized in blood vessels and nerves of the GI tract. Activation of CGRP receptors (subtypes 1 or 2) usually induces vasodilation and/or muscle relaxation, but its effects in dog and on gastroduodenal motility are still unclear. This study looked for the effect of CGRP and the antagonist CGRP8-37, specific for CGRP type 1 receptor, 1) on GI motility (interdigestive and postprandial), and 2) on hemodynamy, in conscious dogs. During the interdigestive period, the infusion of CGRP1-37 (200 pmol/kg/h) or CGRP8-37 (2000 pmol/kg/h) did not modify the duration of the migrating motor complex nor the release nor the motor action of plasma motilin. The gastric emptying of a solid meal (15 g meat/kg) was reduced by the administration of CGRP1-37 (AUC: 2196 +/- 288.6 versus 3618 +/- 288.4 with saline or T12: 78 +/- 7.3 versus 50 +/- 4.3 min; P < 0.01) and this effect was reversed by the antagonist CGRP8-37. CGRP1-37 significantly (P < 0. 01) diminished arterial pressures (118 +/- 1.6/64 +/- 1.4 vs. 125 +/- 1.4/75 +/- 1.2 mmHg with saline) and accelerated the basal cardiac rhythm (110 +/- 1.4 versus 83 +/- 1.6 beats/min). However, CGRP8-37 failed to block the cardiovascular effects of CGRP1-37. In dog, CGRP could influence digestive motility by slowing the gastric emptying of a meal through an action on CGRP-1 receptors. Hemodynamic effects of CGRP were not blocked by CGRP8-37 and seem therefore mediated by CGRP-2 receptor subtype. |
2,332,658 | Disease-related syncope. Analysis of a community-based hospital registry. | Syncope is characterized by sudden and transient loss of consciousness that follows a reduction or interruption of cerebral blood flow. The present study was designed to assess the prevalence of disease-related syncope in a wide sample of in-patients admitted for different diseases. A total of 16 809 patients (age range 18-99 years) were recruited from three hospitals in Florence in 1998. The community-based registry was reviewed to identify all patients suffering from complaints associated with syncope. Each disease-related syncope was matched with the number of patients suffering from that disease. Furthermore, each disease was expressed as a percentage of total cases included in the study. The odds ratio was calculated to determine the index of significant correlation between syncope and occasional diseases. Total syncopes were 775 (prevalence 4.46%), vasovagal syncopes were 336 (1.9% of total sample and 44% of total syncopes), and the disease-related syncopes were 439 (56% of total syncopes). We found a significant association between syncope and orthostatic hypotension, complete heart block, chronic cerebral disease, migraine, acute gastrointestinal haemorrhages and aortic stenosis. Furthermore, we found a significant association with acute gastrointestinal haemorrhage, which has not been described previously. Significant relationships emerged from our data which yield a new insight into the association between syncope and a wide range of systemic diseases. |
2,332,659 | A rapid food screener to assess fat and fruit and vegetable intake. | The U.S. Preventive Services Task Force recommends that Americans lower dietary fat and cholesterol intake and increase fiber and fruit/vegetables to reduce prevalence of heart disease, cancer, stroke, hypertension, obesity, and non-insulin-dependent diabetes mellitus in the United States. To provide preventive services to all, a rapid, inexpensive, and valid method of assessing dietary intake is needed.</AbstractText>We used a one-page food intake screener based on national nutrition data. Respondents can complete and score the screener in a few minutes and can receive immediate, brief feedback. Two hundred adults self-administered the food screener. We compared fat, fiber, and fruit/vegetable intake estimates derived from the screener with estimates from a full-length, 100-item validated questionnaire.</AbstractText>The screener was effective in identifying persons with high-fat intake, or low-fruit/vegetable intake. We found correlations of 0.6-0.7 (p<0. 0001) for total fat, saturated fat, cholesterol, and fruit/vegetable intake. The screener could identify persons with high percentages of calories from fat, total fat, saturated fat, or cholesterol, and persons with low intakes of vitamin C, fiber, or potassium.</AbstractText>This screener is a useful tool for quickly monitoring patients' diets. The health care provider can use it as a prelude to brief counseling or as the first stage of triage. Persons who score poorly can be referred for more extensive evaluation by low-cost paper-and-pencil methods. Those who still have poor scores at the second stage ultimately can be referred for in-person counseling.</AbstractText> |
2,332,660 | Local anaesthesia for awake fibreoptic nasotracheal intubation. | Awake fibreoptic nasotracheal intubation (FNI) is performed in potentially difficult airways under local anaesthesia. This observer-blinded study was designed to evaluate the efficacy of upper airway anaesthesia produced by nebulized lignocaine against combined regional block (CRB) for awake FNI.</AbstractText>Forty-eight ASA 1 adults were randomly allocated to receive 4 ml of 4%-nebulized lignocaine (nebulization group) or translaryngeal block, bilateral superior laryngeal nerve block and three 4% lignocaine-soaked cotton swabs in the nose (CRB group). Facial grimace and patient comfort were assessed by grimace and airway reactivity scores. Patients reported their discomfort on a 4-point score.</AbstractText>All patients underwent successful FNI without significant discomfort; 79% in the nebulization group and 83% of the patients in the CRB group reported the procedure to be comfortable. A higher grimace score was recorded on insertion of the endotracheal tube (ETT) through the nostril in the nebulization group when compared to the CRB group, P<0.005. Similarly, patients in the CRB group were more comfortable during passage of the ETT into the glottis, as compared to the nebulization group. A progressive increase in heart rate was observed in all patients from the beginning of the procedure, but the rise in the nebulization group was greater, (P<0.05) and also lasted longer than in the CRB group (P<0.05). Mean arterial pressure was higher in the nebulization group when compared to the CRB group (P<0.05), with patients belonging to the CRB group demonstrating considerable haemodynamic stability.</AbstractText>Both nebulization and CRB produced satisfactory anaesthesia of the upper airway, but CRB provided better patient comfort and haemodynamic stability.</AbstractText> |
2,332,661 | Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. | We have identified a 35 amino acid peptide toxin of the inhibitor cysteine knot family that blocks cationic stretch-activated ion channels. The toxin, denoted GsMTx-4, was isolated from the venom of the spider Grammostola spatulata and has <50% homology to other neuroactive peptides. It was isolated by fractionating whole venom using reverse phase HPLC, and then assaying fractions on stretch-activated channels (SACs) in outside-out patches from adult rat astrocytes. Although the channel gating kinetics were different between cell-attached and outside-out patches, the properties associated with the channel pore, such as selectivity for alkali cations, conductance ( approximately 45 pS at -100 mV) and a mild rectification were unaffected by outside-out formation. GsMTx-4 produced a complete block of SACs in outside-out patches and appeared specific since it had no effect on whole-cell voltage-sensitive currents. The equilibrium dissociation constant of approximately 630 nM was calculated from the ratio of association and dissociation rate constants. In hypotonically swollen astrocytes, GsMTx-4 produces approximately 40% reduction in swelling-activated whole-cell current. Similarly, in isolated ventricular cells from a rabbit dilated cardiomyopathy model, GsMTx-4 produced a near complete block of the volume-sensitive cation-selective current, but did not affect the anion current. In the myopathic heart cells, where the swell-induced current is tonically active, GsMTx-4 also reduced the cell size. This is the first report of a peptide toxin that specifically blocks stretch-activated currents. The toxin affect on swelling-activated whole-cell currents implicates SACs in volume regulation. |
2,332,662 | Regulation of contraction and relaxation by membrane potential in cardiac ventricular myocytes. | Control of contraction and relaxation by membrane potential was investigated in voltage-clamped guinea pig ventricular myocytes at 37 degrees C. Depolarization initiated phasic contractions, followed by sustained contractions that relaxed with repolarization. Corresponding Ca(2+) transients were observed with fura 2. Sustained responses were ryanodine sensitive and exhibited sigmoidal activation and deactivation relations, with half-maximal voltages near -46 mV, which is characteristic of the voltage-sensitive release mechanism (VSRM) for sarcoplasmic reticulum Ca(2+). Inactivation was not detected. Sustained responses were insensitive to inactivation or block of L-type Ca(2+) current (I(Ca-L)). The voltage dependence of sustained responses was not affected by changes in intracellular or extracellular Na(+) concentration. Furthermore, sustained responses were not inhibited by 2 mM Ni(2+). Thus it is improbable that I(Ca-L) or Na(+)/Ca(2+) exchange generated these sustained responses. However, rapid application of 200 microM tetracaine, which blocks the VSRM, strongly inhibited sustained contractions. Our study indicates that the VSRM includes both a phasic inactivating and a sustained noninactivating component. The sustained component contributes both to initiation and relaxation of contraction. |
2,332,663 | [Perinatal morbidity and mortality secondary to systemic lupus erythematosus in a tertiary care institution]. | Autoimmune diseases occur more often in procreation age women, being systemic lupus erythematosus (SLE) a multisystemic, chronic inflammatory illness, the prototype of them.</AbstractText>Evaluate the behavior of perinatal morbidity/mortality in a group of pregnant patients, identifying maternal and secondary neonatal complications secondary to SLE.</AbstractText>Between January 1992 and December 1997, seventy two cases of maternal SLE were seen at the Instituto Nacional de Perinatología in Mexico City. Maternal and neonatal files were reviewed retrospectively in search of maternal and neonatal complications secondary to SLE.</AbstractText>Maternal SLE diagnosis was confirmed in all cases: Ideal reproductive age was seen in 84.7% and extreme ages in 15.3% of the maternal population. Effective prenatal control was carried out in 87% of the pregnancies and 16.6% required at least one hospitalization during gestation. The most frequent complications were infectious (37.5%), haematologic (13.9%) and renal (5.5%). No mortality was seen in the maternal population. Normal weight for gestational age was seen in 58.3% of the neonates and low weight for gestational age in 41.6%; prematurity was seen in the same percentage (41.6%). The most frequent complications in the neonatal population were haematologic (18.0), respiratory (12.5%), metabolic (8.3%) and heart block and cutaneous lesions (1.4%). Neonatal lupus was diagnosed in 8.3%, and survival was of 94.4%).</AbstractText>Maternal and neonatal morbidity secondary to SLE was seen in less than 50% of the cases. Infectious complications, the most frequent in the maternal population, is probably secondary to medical treatment. Of the patients with neonatal lupus only 2.8% had heart block and cutaneous lesions. Maternal outcome and neonatal repercussion of maternal SLE do not differ in relation to other authors results. However it is necessary to evaluate the immunologic behavior and genetic predisposition because each population has a different of HLA antigens.</AbstractText> |
2,332,664 | Effects of epidural anesthesia on the cardiovascular response to a rapid increase in isoflurane concentration. | To compare circulatory variables to an abrupt increase in isoflurance concentration via mask in patients who received either upper thoracic or lumbar epidural anesthesia, or neither.</AbstractText>Prospective study.</AbstractText>Operating room at a university hospital.</AbstractText>45 ASA physical status I female patients scheduled for elective surgeries with general anesthesia.</AbstractText>Patients received thoracic (TEA group) or lumbar (LEA group) epidural anesthesia, or neither (control group) (n = 15 per group). An epidural catheter was inserted through the T1-T2 intervertebral space in the TEA group or L2-L3 in the LEA group, and 10 mL of 2% lidocaine without epinephrine was injected. Two minutes after induction of anesthesia with thiamylal, the inspired isoflurane concentration was rapidly increased from 0.5% to 5% and maintained for 5 minutes.</AbstractText>Heart rate and mean arterial pressure (MAP) were measured every minute. Mean analgesic levels obtained by epidural block were C4-T6 and T10-S1 in the TEA and LEA groups, respectively. Heart rate increased after the increase in isoflurane concentration in all groups, but increased significantly less in the TEA group than in the control or LEA groups (p < 0.05). Isoflurane also increased MAP in the control group throughout the 5-minute period, but only at the first minute of inhalation in the TEA and LEA groups. The increases in MAP in the TEA and LEA groups were significantly less than that in the control group (p < 0.05).</AbstractText>Epidural anesthesia can blunt circulatory responses to a sudden increase in isoflurane concentration.</AbstractText> |
2,332,665 | Performance of ordered-subset reconstruction algorithms under conditions of extreme attenuation and truncation in myocardial SPECT. | We studied the bias and variance characteristics of the ordered-subset expectation maximization (OSEM) and rescaled block-iterative EM (RBIEM) iterative reconstruction algorithms in myocardial SPECT under extreme, but realistic, conditions.</AbstractText>We used the 2-dimensional mathematic cardiac torso phantom to simulate 2 patient anatomies: a large male with a raised diaphragm and a female with large breast size, approximating extreme cases of attenuation conditions found in the clinic. For each anatomy, realistic 201Tl projection data were simulated for a 180 degrees acquisition arc. Three cases of truncation for a 90 degrees-configured dual detector system were simulated: no truncation, moderate truncation, and extreme truncation. For each case, an ensemble of 250 noise simulations was generated, and each noisy dataset was reconstructed with the OSEM and RBIEM algorithms. The reconstructions modeled only the effects of nonuniform attenuation and used a range of subset configurations. Over the ensemble, we computed means and variances of activity in 8 regions of interest (ROIs) in the heart as a function of iteration.</AbstractText>Under conditions of no truncation and moderate truncation, the results from OSEM and RBIEM were very close to those from maximum-likelihood EM (MLEM); in all cases, the difference in ROI means was <2.5%. For extreme truncation, the errors increased to as much as 11% with OSEM, but these were no greater than the errors for MLEM under the same conditions. The OSEM algorithm with 2 views per subset was found to result in much higher variance of ROI estimates for the same bias as compared with RBIEM or OSEM with 4 or more views per subset.</AbstractText>The OSEM and RBIEM algorithms are at least as robust to highly attenuating patients and truncation as MLEM algorithm and can be adequate substitutes for MLEM, even in extreme cases. Clinical users should apply the smallest number of subsets that can be accommodated by allowable processing time to reduce image noise and variance in quantitative estimates.</AbstractText> |
2,332,666 | Effect on acute rejection reaction and survival of the heart with the addition of dextran 60 to conventional immunosuppressive therapy in an experimental model of heterotopic heart transplantation. | Rejection reaction is an important complication in heart transplantation. Recent physiopathological findings suggest new immunosuppressive alternatives such as the use of substances that block interaction between leukocytes and endothelium or subsequent events. The objective of this work was to evaluate the effect of the combination of dextran 60 and conventional immunosuppressive therapy.</AbstractText>We used Sprague-Dawley rats, both sexes, with mean weight of 317.3 +/- 31.3 g on which we carried out heterotopic heart transplantation and then randomized into four groups. All groups received cyclosporine (2 mg/kg/day) and prednisone (0.5 mg/day). Group I (n = 5) also received 0.5 cc/kg/day of dextran 60, group II (n = 5) 1.0 cc/kg/day of dextran 60, group III (n = 5) 2 cc/kg/day, and group IV (n = 4) 0.9% saline solution 0.5 cc/kg/day. The incidence and severity of rejection reaction was evaluated as survival of transplanted hearts.</AbstractText>Significant differences were found between groups III and IV for incidence of rejection reaction (p = 0.039). However, there were no differences among groups (grade 3A or 3B) in the magnitude of the rejection reaction. Survival of hearts was better in all groups receiving dextran 60 (p = 0.031).</AbstractText>It was concluded that dextran 60 improves survival of transplanted hearts and decreases incidence of rejection reaction.</AbstractText> |
2,332,667 | p53, p21(WAF1/CIP1), and MDM2 involvement in the proliferation and apoptosis in an in vitro model of conditionally immortalized human vascular smooth muscle cells. | Using an in vitro model of a conditionally immortalized cell line, we have investigated how human vascular smooth muscle cells (VSMCs) are affected by the expression of simian virus 40 (SV40) large T antigen (LT antigen), which binds to cell cycle regulators such as the tumor suppressor protein p53. Cells were obtained after infection of saphenous vein-derived VSMCs with a nonreplicative retroviral vector containing a temperature-sensitive mutant of SV40 LT antigen and were shown to have maintained some characteristics and responses of VSMCs. Under permissive-temperature conditions (36 degrees C), the increased rate of cell proliferation was shown to be associated with expression of LT antigen and with LT antigen binding to and inactivation of p53. p53 inactivation failed to block apoptosis induced by serum withdrawal or UV irradiation. Downregulation of LT antigen expression at a nonpermissive temperature (39 degrees C) was shown to be associated with growth arrest, increased expression of the cell cycle inhibitor p21(WAF1/CIP1), increased murine double minute-2 promoter activity, and differential expression of murine double minute-2 gene products, suggesting that p53-induced transcription/transactivation may be involved in VSMC cycle control but not necessarily in apoptosis. The established SMC line HVTs-SM1 may be a useful model for study of the processes involved in myointimal hyperplasia and cellular aging, as well as for the study of cell cycle control in general. |
2,332,668 | Anesthetic efficacy and heart rate effects of the intraosseous injection of 1.5% etidocaine (1:200,000 epinephrine) after an inferior alveolar nerve block. | The purpose of this study was to determine the anesthetic efficacy and heart rate effects of an intraosseous (IO) injection of 1.5% etidocaine with 1:200,000 epinephrine after an inferior alveolar nerve block.</AbstractText>In a repeated-measures designed study, 48 subjects randomly received 2 combinations of injections at 2 separate appointments. The combinations were an inferior alveolar nerve (IAN) block (with 3% mepivacaine) + IO injection with 1.8 mL of 1.5% etidocaine hydrochloride containing 1:200,000 epinephrine, and an IAN + mock IO injection. The first molar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after the injection. Anesthesia was considered successful when 2 consecutive 80 readings (no subject response) were obtained. Heart rate (pulse rate) was measured with a pulse oximeter.</AbstractText>Lip numbness occurred in 100% of the subjects with both the techniques. For the first molar, anesthetic success for the IAN + mock IO and the IAN + IO etidocaine hydrochloride groups, respectively, were 81% and 100%. The differences were significant (P <.05) when the IAN + IO etidocaine hydrochloride technique was compared with the IAN + mock IO. A mean increase in heart rate of 32 beats/min occurred in 90% of the subjects with the IO injection of the etidocaine hydrochloride solution. In 89% of these subjects, the heart rate returned to within 5 beats of baseline values 4 minutes or less after solution deposition.</AbstractText>The IO injection of 1.8 mL of 1.5% etidocaine hydrochloride with 1:200,000 epinephrine, when used to augment an inferior alveolar nerve block, significantly increased anesthetic success in the first molar. The majority of subjects receiving the IO injection of the etidocaine hydrochloride solution had a transient increase in heart rate.</AbstractText> |
2,332,669 | A bradycardiac agent ZD7288 blocks the hyperpolarization-activated current (I(h)) in retinal rod photoreceptors. | Recently it has been reported that "I(f) channel blockers", which block the hyperpolarization-activated inward current (I(f)) in heart sino atrial node cells, also block the hyperpolarization-activated inward current (I(h)) in other tissues. Here we compared the effects of one of these agents, ZD7288 [4-(N-ethyl-N-phenylamino)-1, 2-dimethyl-6-(methylamino) pyrimidinium chloride], with those of Cs(+) on I(h) in amphibian rod photoreceptors using patch clamp and intracellular recordings. ZD7288 strongly inhibited I(h) in newt rod photoreceptors in a concentration-dependent manner (1-100 microM). ZD7288 exerted a blocking action on the conductance of I(h) with no alteration of its gating properties, and the blocking action of I(h) was not use-dependent. At concentrations as low as 1 microM, ZD7288 markedly enhanced the hyperpolarizing membrane responses of frog rod photoreceptors to bright light and delayed the response recovery, indicating that ZD7288 is highly selective for I(h). The apparent effect of the drug was slow in onset and irreversible, suggesting that ZD7288 act at a cytosolic site on the I(h) channel. These observations also confirm the involvement of I(h) in accelerating the response recovery process from deep membrane hyperpolarization induced by bright light in rod cells. |
2,332,670 | Anaplerosis of the citric acid cycle: role in energy metabolism of heart and skeletal muscle. | Efficient energy transfer in heart and skeletal muscle requires a series of moiety-conserved cycles. The intermediaries of the metabolic cycles are finely regulated to maintain a dynamic state of equilibrium. In heart muscle, depletion of the citric acid cycle (TCA cycle) through a block of 2-oxoglutarate dehydrogenase results in a rapid decline of contractile function, which is reversed by the addition of substrates promoting flux through the carboxylating enzymes, malic enzyme, pyruvate carboxylase and propionyl-CoA carboxylase. Anaplerosis describes a pathway, which replenishes a metabolic cycle. We show that enzymes for anaplerosis of the TCA cycle are expressed in heart and skeletal muscles. The role of anaplerosis of the TCA cycle in skeletal muscle is not entirely clear, but there is substantial evidence for its operational control during exercise. While the anaplerotic flux of carbon into the TCA cycle exceeds the removal of cycle intermediates, this process is only transient and reverses with prolonged exercise. It remains to be determined, however, whether the initial increase in TCA cycle intermediates is obligatory in order to attain high rates of TCA cycle flux, or primarily reflects a mass action phenomenon owing to increased substrate availability for anaplerotic pathways. |
2,332,671 | Cytokine-induced nitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes. | The present study examined whether nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) can directly inhibit aerobic energy metabolism and impair cell function in interleukin (IL)-1beta,-stimulated cardiac myocytes.</AbstractText>Recent reports have indicated that excessive production of NO induced by cytokines can disrupt cellular energy balance through the inhibition of mitochondrial respiration in a variety of cells. However, it is still largely uncertain whether the NO-induced energy depletion affects myocardial contractility.</AbstractText>Primary cultures of rat neonatal cardiac myocytes were prepared, and NO2-/NO3- (NOx) in the culture media was measured using Griess reagent.</AbstractText>Treatment with IL-1beta (10 ng/ml) increased myocyte production of NOx in a time-dependent manner. The myocytes showed a concomitant significant increase in glucose consumption, a marked increase in lactate production, and a significant decrease in cellular ATP (adenosine 5'-triphosphate). These metabolic changes were blocked by co-incubation with N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis. Sodium nitroprusside (SNP), a NO donor, induced similar metabolic changes in a dose-dependent manner, but 8-bromo-cyclic guanosine 3',5'-monophosphate (8-bromo-cGMP), a cGMP donor, had no effect on these parameters. The activities of the mitochondrial iron-sulfur enzymes, NADH-CoQreductase and succinate-CoQreductase, but not oligomycin-sensitive ATPase, were significantly inhibited in the IL-1beta, or SNP-treated myocytes. Both IL-1beta and SNP significantly elevated maximum diastolic potential, reduced peak calcium current (I(Ca)), and lowered contractility in the myocytes. KT5823, an inhibitor of cGMP-dependent protein kinase, did not block the electrophysiological and contractility effects.</AbstractText>These data suggest that IL-1beta-induced NO production in cardiac myocytes lowers energy production and myocardial contractility through a direct attack on the mitochondria, rather than through cGMP-mediated pathways.</AbstractText> |
2,332,672 | Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris. Clinical results from the Norwegian randomized trial. | The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris.</AbstractText>Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published.</AbstractText>One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2.</AbstractText>Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.)</AbstractText>Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.</AbstractText> |
2,332,673 | The effect of oral etilefrine premedication on the incidence of hypotension during spinal anaesthesia. | This study was designed to determine the efficacy of oral etilefrine in preventing hypotension induced by spinal anaesthesia. Forty patients, ASA grade I or II, aged 23-60 years, scheduled for orthopaedic surgery involving the lower extremity under spinal anaesthesia were studied. The patients were randomly allocated to one of two groups; the etilefrine group (n = 20) received oral etilefrine 15 mg (30 drops), 60 min before the subarachnoid block, and the control group (n = 20) received no etilefrine. Patients were given 0.5% isobaric bupivacaine intrathecally. Hypotension was defined as a 30% decrease from base-line for systolic arterial pressure and mean arterial pressure or systolic value <90 mmHg, and was treated with intravenous boluses of etilefrine 2 mg. The overall incidence of spinal anaesthesia induced hypotension was 25%, ranging from 20% in the etilefrine group to 30% in the control group. The fall in systolic arterial pressure and mean arterial pressure was significantly greater in the control group than in the etilefrine group (P < 0.05). The patients in the etilefrine group received less etilefrine supplement than those in control group and no subject in the etilefrine group required repeat etilefrine doses, while in the control group five patients received multiple etilefrine doses (P < 0.05). The mean heart rate remained fairly stable throughout the study periods. We conclude that oral etilefrine, given 60 min before surgery, reduces the fall in blood pressure during spinal anaesthesia. |
2,332,674 | Haemodynamic effects of a left stellate ganglion block in ASA I patients. An echocardiographic study. | In anaesthetized dogs, stellate ganglion blockade led to a moderate disturbance in left ventricular diastolic function. We investigated the effect of a left-sided block, following injection of 10 mL bupivacaine 0.5%, on echocardiographic variables of ventricular function in eight otherwise healthy patients with sympathetically mediated pain syndromes. After the blockade, heart rate (control: 66+/-3 (mean+/- SEM), block: 64+/-3 min-1) and mean arterial blood pressure (88.5+/-6.0 vs. 84.0+/-8.1 mmHg) were unchanged, but afterload decreased (end-systolic meridional wall stress; 69.6+/-9.9 vs. 59.8+/-7.1, P < 0.05). Stroke volume increased from 71.2+/-8.1 to 79.6+/-7.4 mL, P < 0.05. Variables of systolic function were unchanged, but relaxation was prolonged (isovolumic relaxation time; 71+/-5 vs. 81+/-4 ms, P < 0.05). In patients who were ASA I, there was a small impairment in echocardiographic variables during ventricular relaxation after a left stellate ganglion blockade. This small effect did not compromise ventricular function, and the heart responded with a small stroke volume increase to the simultaneous afterload reduction. |
2,332,675 | A comparison of the hemodynamic effects of paracervical block and epidural anesthesia for labor analgesia. | Both paracervical block (PCB) and epidural analgesia are sometimes associated with hemodynamic effects potentially harmful to the well-being of the fetus. Our study was designed to test the hypothesis that PCB would have a more profound effect on maternal and fetal blood flow than epidural analgesia.</AbstractText>Forty-four healthy primiparous parturients were randomized to receive either PCB (n=21) or epidural analgesia (n= 23) with 25 or 30 mg of bupivacaine, respectively, for labor analgesia. Maternal blood pressure and fetal heart rate were recorded. Blood flow was measured using a color Doppler device. The blood flow measurements consisted of assessment of the pulsatility indices (PI) of the right maternal femoral artery and the main branch of the uterine artery (placental side), the umbilical artery and the fetal middle cerebral artery. The measurements were performed before administration of analgesia and approximately 15-20 min later after the onset of analgesia.</AbstractText>Both methods provided in general good analgesia, but rescue medication was required more often after PCB. Epidural analgesia decreased maternal blood pressure more than PCB and the PI of maternal femoral artery decreased after onset of epidural analgesia, indicating epidural-induced vasodilation. The PI of the uterine artery increased after the onset of PCB, indicating vasoconstriction of this artery. No significant adverse effects or differences in the well-being of the newborn were observed, as indicated by similar Apgar scores and pH-status.</AbstractText>There were small differences in the effects of PCB and epidural analgesia on uteroplacental circulation as well as on maternal hemodynamics. PCB may have a vasoconstrictive effect on the uterine artery. This and the fact that the parturients required rescue analgesia more frequently after PCB than after epidural block speaks for the feasibility of the latter in obstetrics.</AbstractText> |
2,332,676 | Plasma concentration of fentanyl with xenon to block somatic and hemodynamic responses to surgical incision. | Although anesthesia with xenon has been supplemented with fentanyl, its requirement has not been established. This study was conducted to determine the plasma concentrations of fentanyl necessary to suppress somatic and hemodynamic responses to surgical incision in 50% patients in the presence of 0.7 minimum alveolar concentration (MAC) xenon.</AbstractText>Twenty-five patients were allocated randomly to predetermined fentanyl concentration between 0.5 and 4.0 ng/ml during 0.7 MAC xenon anesthesia. Fentanyl was administered using a pharmacokinetic model-driven computer-assisted continuous infusion device. At surgical incision each patient was monitored for somatic and hemodynamic responses. A somatic response was defined as any purposeful bodily movement. A positive hemodynamic response was defined as a more than 15% increase in heart rate or mean arterial pressure more than the preincision value. The concentrations of fentanyl to prevent somatic and hemodynamic responses in 50% of patients were calculated using logistic regression.</AbstractText>The concentration of fentanyl to prevent a somatic response to skin incision in 50% of patients in the presence of 0.7 MAC xenon was 0.72 +/- 0.07 ng/ml and to prevent a hemodynamic response was 0.94 +/- 0.06 ng/ml.</AbstractText>Comparing these results with previously published results in the presence of 70% nitrous oxide, the fentanyl requirement in xenon anesthesia is smaller than that in the equianesthetic nitrous oxide anesthesia.</AbstractText> |
2,332,677 | Interaction between transient metabolically mediated dilatation and pressure induced constriction in the canine coronary artery. | This study explored the interaction between metabolically mediated vasodilatation (ventricular extra-activation) and pressure induced vasoconstriction (transient augmentation of aortic diastolic pressure). Eight dogs having formalin-induced heart block were chronically instrumented with aortic and left ventricular catheters and an electromagnetic flow probe on the left circumflex coronary artery. At a heart rate of 60 beats/min a single ventricular extra-activation introduced at 200 ms after the normal paced beat resulted in a 13 +/- 1% decrease in diastolic coronary vascular resistance index (DCVRI) in the first response beat (D1) and a persistent vasodilatation lasting for five beats (D1-D5). An increase in aortic diastolic pressure (32 +/- 3% for 520 +/- 15 ms) resulted in 13 +/- 2% increase in DCVRI in the D1 which was not evident in subsequent beats. Following a combined intervention, DCVRI in D1 was not significantly different from control but DCVRI did decrease to a greater degree in the subsequent response beats (D2-D7). These data indicate that the responses of two opposing vasoactive stimuli, i.e., pressure induced vasoconstriction and metabolic vasodilatation, were negated in the first response beat. The metabolically mediated vasodilatation was unaltered in the subsequent response beats. |
2,332,678 | Simulated moderate altitude elevates serum erythropoietin but does not increase reticulocyte production in well-trained runners. | The purpose of this study was to investigate whether the modest increases in serum erythropoietin (sEpo) experienced after brief sojourns at simulated altitude are sufficient to stimulate reticulocyte production. Six well-trained middle-distance runners (HIGH, mean maximum oxygen uptake, VO2max = 70.2 ml x kg(-1) x min(-1) spent 8-11 h per night for 5 nights in a nitrogen house that simulated an altitude of 2650 m. Five squad members (CONTROL, mean VO2max= 68.9 ml x kg(-1) x min(-1) undertook the same training, which was conducted under near-sea-level conditions (600 m altitude), and slept in dormitory-style accommodation also at 600 m altitude. For both groups, this 5-night protocol was undertaken on three occasions, with a 3-night interim between successive exposures. Venous blood samples were measured for sEpo after 1 and 5 nights of hypoxia on each occasion. The percentage of reticulocytes was measured, along with a range of reticulocyte parameters that are sensitive to changes in erythropoiesis. Mean serum erythropoietin levels increased significantly (P < 0.01) above baseline values [mean (SD) 7.9 (2.4) mU x ml(-1)] in the HIGH group after the 1st night [11.8 (1.9) mU x ml(-1), 57%], and were also higher on the 5th night [10.7 (2.2) mU x ml(-1), 42%] compared with the CONTROL group, whose erythropoietin levels did not change. After athletes spent 3 nights at near sea level, the change in sEpo during subsequent hypoxic exposures was markedly attenuated (13% and -4% change during the second exposure; 26% and 14% change during the third exposure; 1st and 5th nights of each block, respectively). The increase in sEpo was insufficient to stimulate reticulocyte production at any time point. We conclude that when daily training loads are controlled, the modest increases in sEpo known to occur following brief exposure to a simulated altitude of 2650 m are insufficient to stimulate reticulocyte production. |
2,332,679 | Action potential propagation in inhomogeneous cardiac tissue: safety factor considerations and ionic mechanism. | Heterogeneity of myocardial structure and membrane excitability is accentuated by pathology and remodeling. In this study, a detailed model of the ventricular myocyte in a multicellular fiber was used to compute a location-dependent quantitative measure of conduction (safety factor, SF) and to determine the kinetics and contribution of sodium current (I(Na)) and L-type calcium current [I(Ca(L))] during conduction. We obtained the following results. 1) SF decreases sharply for propagation into regions of increased electrical load (tissue expansion, increased gap junction coupling, reduced excitability, hyperkalemia); it can be <1 locally (a value indicating conduction failure) and can recover beyond the transition region to resume propagation. 2) SF and propagation across inhomogeneities involve major contribution from I(Ca(L)). 3) Modulating I(Na) or I(Ca(L)) (by blocking agents or calcium overload) can cause unidirectional block in the inhomogeneous region. 4) Structural inhomogeneity causes local augmentation of I(Ca(L)) and suppression of I(Na) in a feedback fashion. 5) Propagation across regions of suppressed I(Na) is achieved via a I(Ca(L))-dependent mechanism. 6) Reduced intercellular coupling can effectively compensate for reduced SF caused by tissue expansion but not by reduced membrane excitability. |
2,332,680 | Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. | The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10). |
2,332,681 | A prospective randomized double-blinded controlled study of ropivacaine 0.75% versus bupivacaine 0.5%-mepivacaine 2% for peribulbar anesthesia. | Ropivacaine 1% has recently been used in clinical trials for peribulbar anesthesia. This study aims to compare the safety and the efficacy of ropivacaine 0.75% with that of a 1:1 mixture of bupivacaine 0.5% and mepivacaine 2% for peribulbar anesthesia.</AbstractText>Two thousand patients undergoing peribulbar anesthesia for elective cataract phacoemulsification were prospectively studied over a 1-year period and randomly assigned to 1 of 2 groups according to the local anesthetic used. One thousand patients were administered peribulbar anesthesia with 9 mL of ropivacaine 0.75% plus 1 mL of hyaluronidase (group R), and 1,000 patients received peribulbar anesthesia with 4 mL of bupivacaine 0.5% plus 4 mL of mepivacaine 2% plus 1 mL of hyaluronidase plus 1 mL of sodium bicarbonate (group BM). Peribulbar anesthesia was always accomplished by the same physician by 2 injections of 5 mL each, with a 25-gauge 25-mm needle. Evaluation was performed by another physician blinded to the technique used and included assessment of pain on local anesthetic injection, ocular and eyelid akinesia, need for top-up injections, onset time and duration of anesthesia, intraoperative analgesia, duration of surgery, hemodynamic parameters, and incidence of perioperative complications.</AbstractText>A greater incidence of pain on injection was found in group BM (P<.001). No difference between the groups was found regarding the onset time and the duration of anesthesia. Perioperative analgesia was satisfactory in both groups with no significant difference. Patients in group R showed a reduced need for top-up injection and a better ocular akinesia at 8 and 10 minutes (P<.01). The akinesia of the eyelid was comparable in the 2 groups and complete in all cases at 8 minutes. Cardiac arrhythmias were more frequent in group BM (P<.01). Local complications did not differ between the groups. An increase in mean artierial blood pressure and heart rate was observed in both groups 1 minute after injection of local anesthetic.</AbstractText>Peribulbar anesthesia with ropivacaine provided better ocular akinesia 8 to 10 minutes after block insertion than a bupivacaine-mepivacaine mixture, which reduced the need for top-up injections. Ropivacaine also caused less pain on injection.</AbstractText> |
2,332,682 | Combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia for hip fractures in the elderly. | This prospective randomized study was designed to determine the hemodynamic effects and quality of combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia in the elderly for repair of proximal femoral fractures.</AbstractText>Twenty-nine elderly patients ranging in age from 68 to 97 years were randomly assigned to 2 groups: a spinal anesthesia group with single-shot 3 mL 0.5% plain bupivacaine, and a combined block group with 30 mL lidocaine 1.33% with epinephrine for the posterior lumbar plexus block and 10 mL same mixture for the parasacral block and an iliac crest block with 5 mL lidocaine 1%.</AbstractText>No need for general anesthesia was encountered in either group. Anesthesia was judged unsatisfactory in 1 of 15 patients in the combined block group. The initial decrease of mean arterial pressure was 38% in the spinal group and 27% in the block group and was not significantly different. A more prolonged hemodynamic effect was found in the spinal group, indicated by the more frequent use of ephedrine to stabilize blood pressure (P<.05). Patients over 85 years had a significantly larger decrease in blood pressure than younger patients (P<.01).</AbstractText>Plain bupivacaine spinal anesthesia and combined lumbar/sacral plexus block provided adequate anesthesia for repair of hip fracture in the elderly. Hypotension was induced by both the combined peripheral nerve block and plain bupivacaine spinal anesthesia in aged patients; hypotension was found to be longer lasting after spinal anesthesia and of a larger magnitude in patients over 85 years of age.</AbstractText> |
2,332,683 | The effect of oxytocin on contractility of the equine oesophagus: a potential treatment for oesophageal obstruction. | This study was performed to determine the effect of administration of i.v. oxytocin on the contractility of the musculature associated with the equine oesophagus. Nine clinically normal horses were fitted with a nasogastric tube modified with inflatable latex cuffs. These cuffs were connected to piezoelectric pressure recording devices. Oxytocin in 3 different doses or saline controls were administered i.v. in a randomised block pattern. Systolic blood pressure, ECG, heart rate and nasogastric tube cuff pressures were then measured for 60 min. Administration of oxytocin i.v. at 0.11 and 0.22 iu/kg bwt, resulted in a short-term statistically significant relaxation of the musculature of the equine oesophagus. When oxytocin was administered at 0.11, 0.22 and 0.44 iu/kg bwt, no clinically significant cardiovascular changes were seen. In approximately 5% of the oxytocin administrations, signs of mild short-term abdominal discomfort were observed. In clinical cases of noncomplicated oesophageal obstruction, it is suggested that reduction in tone of oesophageal musculature may result in passage of oesophageal obstructions with reduced risk of oesophageal injury when compared to other traditional treatments. |
2,332,684 | Baroreceptor control of heart rate in the awake toad: peripheral autonomic effectors and arterial baroreceptor areas. | Systemic injection of sodium nitroprusside (30 microg/kg, i.v.) in the awake Bufo paracnemis toad induced a fall in arterial blood pressure and tachycardia. This tachycardia, but not the hypotension, was significantly reduced in toads with bilateral electrolytic lesion of the caudal and commissural regions of the solitary tract nucleus and in animals with transection of the spinal cord, 2 mm below the obex. This indicates that the tachycardia is reflex, depends on the integrity of the solitary tract nucleus and is due to descending spinal autonomic activation. Pretreatment with propranolol (4 mg/kg, i.v.) significantly reduced the tachycardia but did not block it completely, showing the importance of beta-adrenoceptors in its genesis. The reflex increase in heart rate induced by nitroprusside was not statistically significant in animals with bilateral section of the laryngeal nerve, whose baroreceptor fibers originate from the pulmocutaneous artery or in animals in which the bilateral section of the laryngeal nerve was performed together with section of the glossopharyngeal nerves, which incorporate fibers originating from the carotid labyrinth. The reduction of the reflex tachycardia was significant in toads with aortic arch denervation alone or combined with section of the laryngeal nerves or in animals with complete denervation of the three baroreceptors areas. These results suggest that the region of the aortic arch, when submitted to unloading, is the most important baroreceptor zone for cardiac compensation in toads. |
2,332,685 | Fentanyl augments block of sympathetic responses to skin incision during sevoflurane anaesthesia in children. | We studied 61 healthy ASA 1 patients (aged 2-6 yr) to determine if fentanyl affects the minimum alveolar concentration which blocks adrenergic responses to skin incision (MAC-BAR) in 50% of children in the presence of 60% nitrous oxide. Patients were allocated randomly to one of three fentanyl groups to receive 0, 2 or 4 micrograms kg-1. Patients also received sevoflurane at a preselected end-tidal concentration according to an 'up-and-down' design. After a steady-state sevoflurane concentration had been maintained for at least 15 min, fentanyl was given i.v. Skin incision was performed 5 min after administration of fentanyl. The response was considered positive if heart rate (HR) or mean arterial pressure (MAP) increased by 15% or more. The MAC-BAR of sevoflurane was 1.45 MAC (95% confidence intervals 1.25-1.65 MAC), and this was reduced markedly to 0.63 MAC and 0.38 MAC by addition of fentanyl 2 and 4 micrograms kg-1, respectively. A ceiling effect was not observed and there was a significant difference between the 2 and 4 micrograms kg-1 groups. |
2,332,686 | Direct block of inward rectifier potassium channels by nicotine. | Nicotine has been shown to depolarize membrane potential and to lengthen action potential duration in isolated cardiac preparations. To investigate whether this is a consequence of direct interaction of nicotine with inward rectifier K(+) channels which are a key determinant of membrane potentials, we assessed the effects of nicotine on two cloned human inward rectifier K(+) channels, Kir2.1 and Kir2.2, expressed in Xenopus oocytes and the native inward rectifier K(+) current I(K1) in canine ventricular myocytes. Nicotine suppressed Kir2.1-expressed currents at varying potentials negative to -20 mV, with more pronounced effects on the outward current between -70 and -20 mV relative to the inward current at hyperpolarized potentials (below -70 mV). The inhibition was concentration dependent. For the outward currents recorded at -50 mV, the IC50 was 165 +/- 18 microM. Similar effects of nicotine were observed for Kir2.2. A more potent effect was seen with I(K1) in canine myocytes. Significant blockade ( approximately 60%) was found at a concentration as low as 0.5 microM and the IC50 was 4.0 +/- 0.4 microM. The effects in both oocytes and myocytes were partially reversible upon washout of nicotine. Antagonists of nicotinic receptors (mecamylamine, 100 microM), muscarinic receptors (atropine, 1 microM), and beta-adrenergic receptors (propranolol, 1 microM) all failed to restore the depressed currents, suggesting that nicotine acted directly on Kir channels, independent of catecholamine release. This property of nicotine may explain its membrane-depolarizing and action potential duration-prolonging effects in cardiac cells and may contribute in part to its ability to promote propensity for cardiac arrhythmias. |
2,332,687 | Modulation of cardiac inward rectifier K(+)current by halothane and isoflurane. | The cellular mechanisms that underlie general anesthetic actions on the inward rectifier K(+) current (IKir), a determinant of the resting potential in myocardium, are not fully understood. Using the whole-cell patch clamp technique, therefore, we investigated the effects of halothane and isoflurane on IKir in guinea pig ventricular myocytes. At membrane potentials negative to the equilibrium potential for potassium both anesthetics decreased amplitude of the steady-state inward IKir in a concentration- and voltage-dependent manner. The slope conductance was reduced, but the activation kinetics of the inward current were not altered. At potentials positive to the equilibrium potential for potassium, the outward current was increased by both anesthetics, which also caused small depolarizing shifts in the activation curve. With high internal magnesium concentration, the outward current increase by isoflurane was abolished, and the inward current block by halothane was attenuated. Spermine prevented the effects of both anesthetics on IKir at all membrane potentials tested. The results show voltage-dependent modulation of cardiac IKir channel by volatile anesthetics. Distinct modification of anesthetic effects by inward rectification gating agents, magnesium and spermine, suggests anesthetic interactions with the IKir channel protein.</AbstractText>Differential modulation of myocardial inward rectifier potassium current by volatile anesthetics under normal and altered rectification may contribute to the mechanism of dysrhythmic actions by these anesthetics.</AbstractText> |
2,332,688 | A comparison of midazolam, alfentanil and propofol for sedation in outpatient intraocular surgery. | To determine the ideal sedative regimen for intraocular surgery under peribulbar or retrobulbar block. The addition of alfentanil and or propofol to midazolam was evaluated with regard to hemodynamic variables, respiratory rate, pain, anxiety, sedation, postoperative recovery and patient satisfaction.</AbstractText>Eighty two patients aged between 50 and 85 were recruited into this prospective, randomised, double blind study. Patients, in four groups, received 0.015 mg x kg(-1) midazolam, 5 microg x kg(-1) alfentanil and 0.15 mg x kg(-1) propofol; 0.015 mg x kg(-1) midazolam and 0.15 mg x kg(-1) propofol; 0.015 mg x kg(-1) midazolam and 5 microg x kg(-1) alfentanil or 0.015 mg x kg(-1) midazolam alone. Blood pressure, heart rate, respiratory rate, pain, anxiety and sedation scores were measured. Times to discharge from the Post Anesthesia Care Unit (PACU) and Day Surgery Unit (DSU) were documented. A 24 hr telephone interview was carried out to determine patient satisfaction.</AbstractText>Systolic blood pressure of patients in groups that had received alfentanil was 6% lower than that of patients who had not (P<0.05) at the time of insertion of intraocular block. Patients in the alfentanil groups also had lower respiratory rates during the first 15 min after drug administration, but all patients were given supplemental oxygen therefore oxygen saturation was unaffected. Pain scores of patients who had been given alfentanil were lower during the first postoperative hour than those who had not.</AbstractText>The addition of alfentanil to midazolam is advantageous in providing sedation for insertion of intraocular block.</AbstractText> |
2,332,689 | Electrophysiological effect of l-cis-diltiazem, the stereoisomer of d-cis-diltiazem, on isolated guinea-pig left ventricular myocytes. | l-cis-Diltiazem, the stereoisomer of the L-type Ca(2+) channel blocker d-cis-diltiazem, protects cardiac myocytes from ischemia and reperfusion injury in the perfused heart and from veratridine-induced Ca(2+) overload. We determined the effect of l-cis-diltiazem on the voltage-dependent Na(+) current (I(Na)) and lysophosphatidylcholine-induced currents in isolated guinea-pig left ventricular myocytes by a whole-cell patch-clamp technique. l-cis-Diltiazem inhibited I(Na) in a dose-dependent manner without altering the current-voltage relationship for I(Na) (K(d) values : 729 and 9 microM at holding potentials of -140 and -80 mV, respectively). A use-dependent block of I(Na), the leftward shift of the steady-state inactivation curve and the delay of recovery from inactivation suggest that l-cis-diltiazem has a higher affinity for the inactivated state of Na(+) channels. In addition to I(Na), the lysophosphatidylcholine-induced currents were inhibited by l-cis-diltiazem in a similar concentration range. It is suggested that inhibition of both Na(+) channels and lysophosphatidylcholine-activated non-selective cation channels contributes to the cardioprotective effect of l-cis-diltiazem. |
2,332,690 | Ventricular arrhythmias induced by endothelin-1 or by acute ischemia: a comparative analysis using three-dimensional mapping. | To analyze three-dimensional activation patterns of ventricular arrhythmias induced by endothelin-1 in comparison with ischemia-induced tachycardias.</AbstractText>Following AV node ablation, sixty pin electrodes containing four bipoles each were inserted into both ventricles of ten foxhounds. Using a computerized mapping system, this would allow to simultaneously record 240 endo-, epi- and midmyocardial electrograms for reconstruction of the three-dimensional activation pattern. In five dogs, endothelin-1 was infused into the LAD at 60 pmol/min. In another five animals, the LAD was ligated. During the following 40 min, all ventricular arrhythmias were recorded for subsequent analysis. Furthermore, left ventricular conduction times during constant pacing and local effective refractory periods at eight left ventricular sites were determined before and after either intervention.</AbstractText>Endothelin-1 had no significant effect on conduction time and refractoriness, whereas ligation prolonged both parameters significantly. Endothelin-1 as well as ligation induced multiple mono- and polymorphic nonsustained ventricular tachycardias. Endothelin-1-induced arrhythmias were exclusively based on focal mechanisms, whereas during ligation, macroreentrant mechanisms were involved in the maintenance of tachycardias in 29% of episodes.</AbstractText>The differences in the effects of endothelin-1 and LAD ligation on electrophysiologic properties and the difference in the mechanism of induced ventricular tachycardias support the hypothesis that, apart from vasoconstrictive properties, endothelin-1 exerts an intrinsic arrhythmogenic effect.</AbstractText> |
2,332,691 | Treatment with epoprostenol reverts nitric oxide non-responsiveness in patients with primary pulmonary hypertension. | To assess whether long term treatment with epoprostenol might restore primary non-responsiveness to nitric oxide (NO) in patients with primary pulmonary hypertension.</AbstractText>Seven patients with primary pulmonary hypertension receiving intravenous epoprostenol continuously because of failure of NO to influence pulmonary haemodynamics during initial testing were followed over a period of 13-29 months. Afterwards, acute vascular reactivity towards NO was tested again during right heart catheterisation.</AbstractText>Administration of NO after continuous epoprostenol treatment for a mean period of 18 months improved arterial oxygen saturation (p < 0.01) and cardiac index (p < 0.05), and decreased mean pulmonary artery pressure (p < 0.01) and total pulmonary vascular resistance (p < 0.01) in patients previously unresponsive to NO.</AbstractText>Long term treatment with epoprostenol reverts initial refractoriness to NO in patients with primary pulmonary hypertension. Thus the addition of NO to epoprostenol treatment might cause further improvement in the course of the disease.</AbstractText> |
2,332,692 | Role of nitric oxide in the control of the heart rate within the nucleus ambiguus of rats. | The aim of this study was to determine whether NO plays a role in the control of heart rate (HR) within the nucleus ambiguus (NA). Experiments were performed in 29 male Wistar rats anaesthetized with urethane. Microinjections of the NO-donor sodium nitroprusside (SNP; 5 mmol) as well as of L-arginine (L-arg; 50 mmol) into functionally identified cardioinhibitory sites within the NA significantly decreased HR (-57.7 +/- 8.4 and -53.8 +/- 3.2 bpm, respectively), whereas the NO-synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly increased HR (+40 +/- 2.7 bpm). Bilateral vagotomy and i.v. injection of atropine (0.5mg/kg) always abolished the HR decrease induced by SNP and L-arg, whereas propranolol did not affect the HR responses. These results demonstrated that NO mechanisms within the NA play a role in the parasympathetic control of the HR. |
2,332,693 | Less adrenergic activation during cataract surgery with total intravenous than with local anesthesia. | Previous studies reported that, contrary to local anesthesia, cataract surgery under inhalational anesthesia is associated with substantial adrenergic activation. We tested the hypothesis that total intravenous anesthesia (TIVA) with propofol and alfentanil produces less or comparable adrenergic activation during cataract surgery than local anesthesia.</AbstractText>Patients were randomly assigned to peribulbar local block (n=10) or TIVA (n=10). The heart rate, blood pressure, plasma concentrations of catecholamines, cortisol, and glucose were assessed at seven pre-, intra-, and post-operative time points.</AbstractText>In the patients given local anesthesia, plasma concentrations of epinephrine, norepinephrine and cortisol did not change significantly. In contrast, plasma epinephrine decreased by roughly 66% during TIVA: from 45+/-16 to 15+/-8 pg/ml. Plasma norepinephrine concentration decreased by roughly 50%, from 462+/-265 to a minimum value of 219+/-6 pg/ml and plasma cortisol concentrations decreased by roughly 61%, from 16.4 ng/ml to 6.4 ng/ml. Blood pressure and heart rates remained near baseline values during local anesthesia. In contrast, systolic blood pressure decreased by 30% and heart rate by 12 beats/min during TIVA.</AbstractText>The presented study and available data clearly suggest that local anesthesia produces the best adrenergic and hemodynamic stability during cataract surgery. Contrary to previously reported results on inhalational anesthesia (thiopentone/enflurane), the TIVA regimen used effectively prevents the adrenergic and metabolic response during cataract surgery.</AbstractText> |
2,332,694 | Protein kinase C enhances the rapidly activating delayed rectifier potassium current, IKr, through a reduction in C-type inactivation in guinea-pig ventricular myocytes. | 1. The rapidly activating delayed rectifier potassium current, IKr, was studied in guinea-pig ventricular myocytes in the presence of thiopentone, which blocks the more slowly activating component of the delayed rectifier potassium current, IKs, and using whole cell perforated patch clamp or switched voltage clamp with sharp electrodes to minimise intracellular dialysis. 2. Activation of protein kinase A (PKA) by isoprenaline or forskolin caused an increase in IKr tail currents. Following a 300 ms depolarising step to +20 mV, mean tail current amplitude was increased 47 +/- 12% by isoprenaline, and 73 +/- 13% by forskolin. No increase in IKr was observed when IKr was studied using whole cell ruptured patch clamp and there was no change in the reversal potential of IKr in the presence of isoprenaline. 3. The rectification of the current sensitive to E4031, a selective IKr blocker, was markedly reduced in the presence of isoprenaline and the region of negative slope was absent. This is consistent with a reduction in the inactivation of IKr and was supported by the finding that IKr, in the presence of isoprenaline, was somewhat less sensitive to block. E4031 (5 microM) blocked only 81 +/- 5% of IKr in the presence of isoprenaline compared to 100 +/- 0% in control. 4. The forskolin- and isoprenaline-induced increases in IKr were inhibited by staurosporine and by the selective protein kinase C (PKC) inhibitor bisindolymaleimide I. Direct activation of PKC by phorbol dibutyrate increased IKr tail currents by 24 +/- 5%. Both the isoprenaline- and forskolin-induced increases in IKr were inhibited when calcium entry was reduced by block of ICa with nifedipine or when myocytes were pre-incubated in BAPTA-AM. 5. The selective PKA inhibitor KT5720 prevented the isoprenaline-induced increase in IKr only when the increase in ICa was also suppressed. 6. These data show a novel mechanism of regulation of IKr by PKC and this kinase was activated by beta-adrenoceptor stimulation. IKr seems to be enhanced through a reduction in the C-type inactivation which underlies the rectification of the channel and such a mechanism may occur in other channels with this type of inactivation. |
2,332,695 | Role of muscarinic cholinergic transmission in Edinger-Westphal nucleus-induced choroidal vasodilation in pigeon. | Activation of the parasympathetic ciliary ganglion input to the choroid causes increases in choroidal blood flow. We examined the role and the type of muscarinic receptors within the choroid that are involved in these increases in choroidal blood flow, using electrical stimulation of the nucleus of Edinger-Westphal (EW) to activate the ciliary ganglion input to choroid in ketamine anesthetized pigeons. Baseline choroidal blood flow and its EW-evoked increases measured as peak and total (area under the curve) responses were determined using laser Doppler flowmetry. The EW-evoked responses were reduced dose-dependently after administration of 4-diphenyl-acetoxy-N-methylpiperedine (4-DAMP), a relatively selective antagonist of M3 type muscarinic receptors, with a maximal mean decrease of 86% (peak response) and 93% (total response) at a dose of 10 microg kg(-1)i.v. without a significant effect on baseline choroidal blood flow, heart rate or systemic arterial blood pressure. Atropine, a non-selective antagonist of muscarinic receptors, decreased the EW-evoked responses to a lesser extent than 4-DAMP after intravenous administration of 1 mg kg(-1)(by 67% for peak response and by 53% for total response) or topical administration of a 5% solution (by 41% for peak response and by 62% for total response), both of which increased heart rate and systemic arterial blood pressure without a consistent effect on baseline choroidal blood flow. In contrast, himbacine (i.p. 10 microg kg(-1)), a relatively selective antagonist of M2 type muscarinic receptors, increased the EW-evoked parasympathetic cholinergic vasodilation (by 93% for the peak response and by 142% for the total response) without a significant effect on heart rate, systemic arterial blood pressure or baseline choroidal blood flow. The results of our study suggest a major role of M3 type muscarinic receptors in the EW-evoked increases in choroidal blood flow. Based on findings that the ciliary ganglion input to choroid does not synthesize nitric oxide but inhibitors of NO production do block EW-evoked choroidal vasodilation, it seems likely that the M3 receptors acted on by 4-DAMP are present on choroidal endothelial cells and mediate choroidal vasodilation via stimulation of endothelial release of nitric oxide. In contrast, M2 muscarinic receptors may play a presynaptic role in downregulating EW-evoked parasympathetic cholinergic vasodilation in avian choroid. |
2,332,696 | p53, p21(WAF1/CIP1), and MDM2 involvement in proliferation and apoptosis in an in vitro model of conditionally immortalized human vascular smooth muscle cells. | Using an in vitro model of a conditionally immortalized cell line, we investigated how human vascular smooth muscle cells (VSMCs) are affected by the expression of simian virus 40 (SV40) large T antigen (LT antigen), which binds to cell cycle regulators, such as the tumor suppressor protein p53. Cells were obtained after infection of saphenous vein-derived VSMCs with a nonreplicative retroviral vector containing a temperature-sensitive (ts) mutant of SV40 LT antigen and were shown to have maintained some characteristics and responses of VSMCs. Under permissive temperature conditions (36 degrees C), the increased rate of cell proliferation was shown to be associated with expression of LT antigen and with LT-antigen binding to and inactivation of p53. p53 inactivation failed to block apoptosis induced by serum withdrawal or by UV irradiation. Downregulation of LT-antigen expression at the nonpermissive temperature (39 degrees C) was shown to be associated with growth arrest, increased expression of the cell cycle inhibitor p21(WAF1/CIP1), increased MDM2-promoter activity, and differential expression of MDM2 gene products, suggesting that p53-induced transcription/transactivation may be involved in VSMC cell cycle control but not necessarily apoptosis. The established SMC line HVTs-SM1 may be a useful model for the study of processes involved in myointimal hyperplasia and cellular aging, as well as for the study of cell cycle control in general. |
2,332,697 | Portuguese Man-of-war (Physalia physalis) venom induces calcium influx into cells by permeabilizing plasma membranes. | Portuguese Man-of-war (Physalia physalis) nematocyst venom dose-dependently stimulates calcium (45Ca(2+)) influx into L-929, GH(4)C(1), FRL, and embryonic chick heart cells. Venom-induced calcium influx is not blocked by ouabain, vanadate, nor organic calcium channel blockers, but is blocked by transition metal cations, such as lanthanum and zinc. Venom-induced calcium influx is accompanied in a dose-dependent manner by the release of intracellular lactate dehydrogenase, indicating a loss in plasma membrane integrity and cytolysis. Concentrations of zinc that block 45Ca(2+) influx also block lactate dehydrogenase release. Lanthanum, which also blocks 45Ca(2+) uptake, does not neutralize the cytolytic activity of the venom, but rather inhibits the venom's cytolytic action at the level of the target cell plasma membrane. Our findings indicate that Man-of-war venom causes an influx of calcium into several different cells types, not just those of the cardiovascular system, and this influx likely occurs by permeabilizing the plasma membranes of cells. |
2,332,698 | Paradoxical block of the Na+-Ca2+ exchanger by extracellular protons in guinea-pig ventricular myocytes. | 1. The Na+-Ca2+ exchange is a major pathway for removal of cytosolic Ca2+ in cardiac myocytes. It is known to be inhibited by changes of intracellular pH that may occur, for example, during ischaemia. In the present study, we examined whether extracellular protons (pHo) can also affect the cardiac exchange. 2. Na+-Ca2+ exchange currents (INa-Ca) were recorded from single adult guinea-pig ventricular myocytes in the whole-cell voltage-clamp configuration while [Ca2+]i was simultaneously imaged with fluo-3 and a laser-scanning confocal microscope. To activate INa-Ca, intracellular Ca2+ concentration jumps were generated by laser flash photolysis of caged Ca2+ (DM-nitrophen). 3. Exposure of the cell to moderately and extremely acidic conditions (pHo 6 and 4) was accompanied by a decrease of the peak INa-Ca to 70 % and less than 10 %, respectively. The peak INa-Ca was also inhibited to about 45 % of its initial value by increasing pHo to 10. The largest INa-Ca was found at pHo approximately 7.6. 4. Simultaneous measurements of [Ca2+]i and INa-Ca during partial proton block of the Na+-Ca2+ exchanger revealed that the exchange current was more inhibited by acidic pHo than the rate of Ca2+ transport. This observation is consistent with a change in the electrogenicity of the Na+-Ca2+ exchange cycle after protonation of the transporter. 5. We conclude that both extracellular alkalinization and acidification affect the Na+-Ca2+ exchanger during changes of pHo that may be present under pathophysiological conditions. During both extreme acidification or alkalinization the Na+-Ca2+ exchanger is strongly inhibited, suggesting that extracellular protons may interact with the Na+-Ca2+ exchanger at multiple sites. In addition, the electrogenicity and stoichiometry of the Na+-Ca2+ exchange may be modified by extracellular protons. |
2,332,699 | Time-dependent block of the slowly activating delayed rectifier K(+) current by chromanol 293B in guinea-pig ventricular cells. | The slowly activating delayed rectifier K(+) current (I(Ks)) was recorded in single myocytes dissociated from guinea-pig ventricles and the mechanism underlying the block of I(Ks) by a chromanol derivative, 293B, was investigated. In the presence of 1 - 100 microM 293B, activation phase of I(Ks) was followed by a slower decay during 10 s depolarizing pulses. Both the rate and extent of the decay were increased in a concentration-dependent manner. The relationship between the concentration of 293B and the block showed a Hill's coefficient of approximately 1. The half-inhibitory concentration was approximately 3.0 microM and did not differ significantly at various membrane potentials from +20 to +80 mV. A mathematical model for the 293B block was constructed on the basis of multiple closed and open states for the I(Ks) channels, and the blocking rate was calculated by fitting the model to the original current traces. The blocking rate constant showed a linear function with the 293B concentration, indicating 1 : 1 binding stoichiometry. At +80 mV the blocking rate was 4x10(4) M(-1) s(-1) and the unblocking rate was 0.2 s(-1). The results indicate that 293B is an open channel blocker with relatively smaller blocking rate than those reported so far for time-dependent blockade of various ionic channels. |
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