Effect of calcium antagonism on contractile behavior of canine hearts

The cardiovascular effects of prenylamine (P), verapamil (V), and nifedipine (N) were studied in open-chest, anesthetized dogs and in isolated, isovolumic dog hearts perfused at constant coronary blood flow (CBF). These drugs significantly decreased left ventricular pressure (LVP) and its maximal rates of rise (+P) and fall (-P). The tension developed by an isometric segment of the left ventricle and its maximal rates of rise (+T) and fall (-T) also decreased, whereas heart rate (HR) did not show statistically significant differences. Maximal rates of fall (-P and -T) were proportionally more depressed than maximal rates of rise (+P and +T), producing significant increments in the ratios between both maximal velocities (+P/-P and +T/-T). The time constant of LVP isovolumic decay tau was significantly prolonged, either in the whole animal or in isolated perfused hearts. The afterload reduction produced by the compounds can account in part for the increase in +P/-P but not for the increase in +T/-T or for the prolongation of tau. These relaxation indices remained unchanged after comparable myocardial depressions elicited by d,l-propranolol or pentobarbital sodium. It is concluded that calcium antagonist compounds are characterized by an "antirelaxant" effect, not explained by changes in HR, CBF, or loading conditions, and independent from their negative inotropic action.