Effects of the Na+ antagonist cibenzoline on left ventricular function of postischemic hearts

Abstract

The negative inotropic effect of antiarrhythmic drugs is a major drawback in antiarrhythmic drug therapy, especially in patients with reduced contractile function of the left ventricle. The circulatory and myocardial effects of the new class I antiarrhythmic drug (a Na+ antagonist), cibenzoline (2 mg/kg i.v.), were investigated in 47 open-chest rats with normal and postischemic myocardium (3 x 4 minutes of global ischemia). Hemodynamic measurements in the intact circulation and isovolumic registrations (peak isovolumic left ventricular systolic pressure and peak isovolumic dP/dtmax) were compared to saline controls. In rats with postischemic myocardium, cibenzoline caused a significant (p < 0.001) decrease in the cardiac output for 38%, in the dP/dtmax for 30%, and in the peak isovolumic dP/dtmax for 19% at the end of infusion (compared to the control). The heart rate was reduced by 22% (p < 0.001), the mean aortic pressure by 22% (p < 0.001), and the calculated systemic resistance by 20% (p < 0.001). In contrast to the results with postischemic myocardium, no important changes in the hemodynamics were detectable after an identical dose in normal animals without left ventricular dysfunction. The results indicate that standard doses of the Na+ antagonist cibenzoline may induce significant cardiodeperessant effects on postischemic left ventricles with reduced function.

Effects of cibenzoline on cardiac function and metabolism in the rat heart-lung preparation

“…Hoffmeister et al . [9] also showed that the mechanism of the increase in heart rate was thought to be due to reflex activation. However, Millar and Vaughan Williams [10] in an in vitro study, described cibenzoline as having a negative chronotropic potential and concluded that negative chronotropic actions could be largely compensated in vivo by sympathetic reflexes.…”

Hemodynamic and inotropic effects of antiarrhythmic drugs used to treat paroxysmal supraventricular arrhythmias

“…Cardiodepressive effects of antiarrhythmic drugs may be an important limitation of this therapeutic procedure since these drugs can aggravate heart failure. In previous in vivo animal studies we could also demonstrate that class-I antiarrhythmic drugs have a cardiodepressive effect and that this effect is especially more pronounced in animals with reduced left ventricular function [ 13,14]. An i.v.…”

“…It was the aim of this study to compare the acute dose-dependent hemodynamic and inotropic effects of short intravenous infusions of the nucleoside adenosine with that of the class I antiarrhythmic drug ajmaline (AJM). We used an open-chest animal model [13][14][15], which permits, besides measurements of circulatory effects in the intact circulation, the determination of direct myocardial effects independently of peripheral vascular effects by isovolumic measurements in vivo.…”