Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Aug 1999
Randomized Controlled Trial Clinical TrialLevosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial.
Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. We tested the hypothesis that levosimendan enhances cardiac performance after cardiopulmonary bypass (CPB). Anesthesia was induced and maintained with midazolam, sufentanil, and vecuronium in 18 patients randomly assigned to receive levosimendan (18 or 36 microg/kg loading dose and 0.2 or 0.3 microg/kg/min infusion, respectively) or placebo 15 min before and continued for 6 h after CPB. ⋯ CO and SV were higher and SVR was lower in patients receiving levosimendan versus placebo after CPB. No differences in arterial oxygenation and perioperative arrhythmias (Holter analysis) were observed between groups. The results indicate that levosimendan enhances cardiac performance after CPB in humans.
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J. Cardiovasc. Pharmacol. · Jul 1999
Comparative StudyElectrophysiologic, cardiohemodynamic and beta-blocking actions of a new ultra-short-acting beta-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol.
The purpose of this study was to assess the cardiovascular effects of an ultra-short-acting beta-blocker, ONO-1101, by using halothane-anesthetized beagle dogs in comparison with esmolol. ONO-1101 (n = 6) or esmolol (n = 6) was administered at four infusion rates of 0.3, 3, 30, and 300 microg/ kg/min. Each infusion was performed over a 30-min period, and the parameters were measured at 20-30 min after the start of each infusion. ⋯ The cardiovascular effects of esmolol were comparable to those of ONO-1101, except that the preload of the left ventricle was significantly increased, and the ventricular repolarization phase was shortened by 300 microg/kg/min of esmolol infusion. Meanwhile, ONO-1101 as well as esmolol significantly reduced the isoproterenol-induced increase in heart rate and ventricular contraction, but the inhibitory action of ONO-1101 was 6-8 times greater than that of esmolol. These results suggest that the suppressive effects of ONO-1101 on cardiovascular performance are significantly less potent than those of esmolol at equipotent beta-blocking doses.
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J. Cardiovasc. Pharmacol. · Apr 1999
Effects of AH-1058, a new antiarrhythmic drug, on experimental arrhythmias and cardiac membrane currents.
AH-1058 is a newly synthesized antiarrhythmic agent. We investigated the antiarrhythmic and electrophysiological effects of AH-1058 in experimental arrhythmia models and isolated cardiomyocytes. In the ouabain-induced arrhythmia model of the guinea pig, pretreatment with AH-1058 (0.1-0.3 mg/kg, i.v.) delayed the appearance of premature ventricular complex (PVC) and ventricular fibrillation (VF) induced by intravenous infusion of ouabain. ⋯ Electrophysiological experiments with patch-clamp techniques revealed that AH-1058 potently suppressed the L-type Ca2+ currents in isolated cardiomyocytes of the guinea pig. These results suggest that AH-1058 is a potent antiarrhythmic drug having a Ca2+ channel-blocking action. The antiarrhythmic profile of AH-1058 is different from that of disopyramide and verapamil.
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J. Cardiovasc. Pharmacol. · Feb 1999
Platelet-derived growth factor-induced vasodilatation in mesenteric resistance arteries by nitric oxide: blunted response in spontaneous hypertension.
Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth-muscle cells, but its effects on vasomotion remain controversial. Both vasoconstriction and vasodilatation of isolated rat aortic rings have been reported. The effects of PDGF on responses of perfused mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rats were studied by using a video dimension analyzer. ⋯ No vasoconstriction was observed after application of PDGF-BB to both normotensive and hypertensive mesenteric arteries with or without endothelium. In rat mesenteric resistance arteries, PDGF induces endothelium-dependent vasodilatation mediated by nitric oxide. At sites where PDGF is released or locally produced, therefore, the growth factor may participate in regulating vascular tone, and this endothelium-dependent regulation is attenuated in spontaneous hypertension.
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J. Cardiovasc. Pharmacol. · Jan 1999
Comparative StudyHemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin.
The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. ⋯ These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the reduction of venous tone by its nitrate properties. Nicorandil may prove to be useful in the treatment of acute ischemic heart failure.