Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Sep 2002
Time-dependent cardioprotection with calcium antagonism and experimental studies with clevidipine in ischemic-reperfused pig hearts: part II.
The intracellular calcium level is increased during ischemia and early reperfusion. The aim of this study was to study the role of the calcium influx in the development of myocardial ischemic and reperfusion injury during the early and late phases of ischemia and during early reperfusion. An ultrashort-acting calcium antagonist, clevidipine, was used as a tool for this investigation. ⋯ In the second set of experiments, there was a similar area at risk and no significant difference in infarct size between the noninfusion group and the 5-minute vehicle infusion group, indicating that the LAD infusion per se did not affect infarct size. The present results demonstrate that blockade of calcium influx by the short-acting dihydropyridine calcium antagonist clevidipine during the early phase of ischemia and at the time of reperfusion, but not during a late phase of ischemia, limits infarct size induced by ischemia and reperfusion. This indicates that the pathophysiological importance of calcium influx varies according to the different phases of myocardial ischemia and reperfusion.
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J. Cardiovasc. Pharmacol. · Aug 2002
Case ReportsTorsadegenic action of the antipsychotic drug sulpiride assessed using in vivo canine models.
A patient had QT prolongation and syncope after starting sulpiride therapy. The present experiments were performed to clarify the causal link among the sulpiride administration, QT prolongation, and the onset of torsade de pointes. Two in vivo models were used: halothane-anesthetized dogs and chronic atrioventricular (AV) block dogs. ⋯ In the chronic AV block animals (n = 4), onset of torsades de pointes with marked QT prolongation was demonstrated after the administration of 60 and 120 mg/kg orally of sulpiride. These results suggest that the QT prolongation and the change in the final repolarization phase with increased sympathetic tone may be the mechanisms responsible for the arrhythmogenic effect of sulpiride. Thus, caution should be paid with the use of sulpiride in patients at risk for elevated plasma concentrations and having preexisting susceptibility to QT prolongation.
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J. Cardiovasc. Pharmacol. · Nov 2001
Comparative Study Clinical TrialAcute hemodynamic effects of beta-blockers in patients with severe congestive heart failure: comparison of celiprolol and esmolol.
The present study was designed to investigate, in patients with severe heart failure, the dose-dependent acute hemodynamic effects of celiprolol versus those of esmolol. Celiprolol is a beta 1 -receptor blocker with vasodilating properties, whereas esmolol is an ultra-short-acting beta 1 -blocker. Included were 14 patients with decompensated chronic heart failure (NYHA class IV) due to coronary heart disease (n = 8) or to dilated cardiomyopathy (n = 6). ⋯ Esmolol caused a significant dose-dependent decrease (-25% below baseline at the highest dose level) in cardiac index (CI). After administration of celiprolol, CI decreased only transiently (-10% below baseline at the second and third dose level) and did not differ from the baseline at the highest dose level. For treatment of severe heart failure, initiation of intravenous beta-blocker therapy with low doses of a beta 1 -blocker with vasodilating effects may have hemodynamic advantages over conventional beta-blockade.
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J. Cardiovasc. Pharmacol. · Apr 2001
Levosimendan increases diastolic coronary flow in isolated guinea-pig heart by opening ATP-sensitive potassium channels.
Levosimendan, a novel calcium sensitizer developed for the treatment of acute heart failure, is an inodilator that increases coronary flow. Because it was recently shown that levosimendan stimulates potassium current through K(ATP) channels in isolated rat arterial cells, our aim was to assess whether the levosimendan-induced increase in coronary flow is due to the opening of the K(ATP) channels in coronary smooth muscle. The effect of levosimendan on the diastolic coronary flow velocity (DCFV) was measured in the Langendorff perfused spontaneously beating guinea-pig heart in the absence and presence of glibenclamide. ⋯ The results indicate that levosimendan induced coronary vasodilation through the opening of the K(ATP) channels. Levosimendan and pinacidil probably have different binding sites on the K(ATP) channels. The additive effect of bisindolylmaleimide and levosimendan on the increase of DCFV suggests that the latter binds to the unphosphorylated form of the channel.
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J. Cardiovasc. Pharmacol. · Apr 2001
ReviewVascular protective effects of angiotensin converting enzyme inhibitors and their relation to clinical events.
Endothelial cells are a rich source of a variety of vasoactive substances, which either cause vasodilation or vasoconstriction. Important endothelium-derived vasodilators are prostacyclin, bradykinin, nitric oxide and endothelium-derived hyperpolarizing factor. In particular, nitric oxide inhibits cellular growth and migration. ⋯ After myocardial infarction ACE inhibitors reduce the development of overt heart failure, the occurrence of reinfarction and cardiovascular death in hypertensive patients. These effects have also been demonstrated in a subgroup analysis of the SOLVD (Studies of Left Ventricular Dysfunction) trial. Thus, in summary, ACE inhibitors are an important class of drugs providing cardiovascular protection in patients with increased cardiovascular risk.