Hemodynamic effects of a new antiarrhythmic agent: cibenzoline

Abstract

The hemodynamic effects of an intravenous dose of 1 mg/kg of Cibenzoline, a new anti-arrhythmic agent with properties of classes I, III and IV of the Vaughan-Williams classification, were studied in 9 patients during routine cardiac catheterization. Six patients had valvular heart disease (aortic insufficiency in 5 and mitral stenosis in 1), one patient had ischemic heart disease, one patient had alcoholic cardiomyopathy and the remaining patient had coarctation of the thoracic aorta. Left ventricular pressure and right sided intracardiac pressures were recorded using a high fidelity transduced and a Swan-Ganz catheter respectively. The first derivative of the left ventricular pressure was obtained electronically and Vmax calculated by linear extrapolation to zero load of the contractile element shortening velocity--left ventricular pressure relationship. Plasma levels of Cibenzoline were measured by gas liquid chromatography. All these parameters were obtained under baseline conditions and then 5, 10, 20, 40 and 60 minutes after intravenous administration of Cibenzoline. Cardiac index fell by 20% 5 minutes after the injection of Cibenzoline, and returned to control after one hour only. This fall was primarily related to a decrease in stroke index, since heart rate remained virtually unchanged. Right and left ventricular filling pressures increased significantly from the 5th to the 40th minute. Aortic systolic pressure fell by approximately 6%, without any change in mean and diastolic aortic pressures. Peripheral and pulmonary resistances increased at 20 minutes by 33% and 45%, respectively. Left ventricular peak positive dP/dt and Vmax decreased significantly at 5 minutes and remained below the baseline value until 60 minutes by 9% and 11% respectively. Percent changes in cardiac index, dP/dt and Vmax were significantly correlated to cibenzoline plasma levels (r = 0.85, 0.79, 0.74 respectively; n = 45). Thus, doses achieving plasma levels within the reported therapeutic range (250-350 ng/ml) would be expected to result in a 8-12% decrease in cardiac output associated with 12-17% and 15-21% reduction of left ventricular dP/dt and Vmax respectively. These data indicate that cibenzoline exerts significant negative inotropic effects. Its use in the subset of patients with severely depressed ventricular function warrants caution.