Hemodynamic effects of cibenzoline on normal myocardium and after pretreatment with DL-sotalol

Abstract

The circulatory and myocardial effects of cibenzoline were investigated in 78 open-chest rats during and after a 7-min intravenous (i.v.) infusion. Measurements were performed in the intact circulation, and myocardial function was also examined by isovolumic registrations independent of circulatory changes. In the first part of the study, the dose-dependent effects of cibenzoline were investigated (2, 4, and 8 mg/kg vs. NaCl controls). Cibenzoline caused a dose-dependent decrease in heart rate (HR) (-16, -34, -37% vs. preinfusion values), mean aortic blood pressure (AoPm) (-8, -20, -30%), cardiac output (CO) (-6, -29, -39%), and dP/dtmax (+1, -21, -59%). The isovolumic peak left ventricular systolic BP (LVSBP) (-6, -6, -17%) and peak dP/dtmax (-8, -18, -54%) were also reduced. In the second part of the study, we examined the effects of 2 mg cibenzoline/kg after pretreatment with 2 mg DL-sotalol/kg: HR was -22% AoPm was -12%, CO was -29%, dP/dtmax was -40%, isovolumic LV pressure (LVP) was -12%, and peak dP/dtmax was -41%. Cibenzoline caused dose-dependent bradycardia, which cannot be explained by beta-adrenoceptor blockade. The auxotonic and isovolumic measurements indicate that cibenzoline possesses a dose-dependent negative inotropic effect: 2 mg cibenzoline/kg caused only a slight decrease in myocardial performance, but this effect was aggravated after pretreatment with DL-sotalol. Cibenzoline also increased peripheral resistance. The observed combination of negative inotropism and vasoconstriction caused by cibenzoline should be taken into consideration especially in patients with reduced LV function. This is of particular importance if cibenzoline is combined with DL-sotalol.