Combined negative inotropic effects of calcium entry blockers and isoflurane on canine isolated heart muscles

Abstract

The combined negative inotropic effects of isoflurane and calcium entry blockers (verapamil, diltiazem, nifedipine, nicardipine) were studied utilizing isolated heart preparations of ventricular muscles from dogs. All of these calcium entry blockers exerted dose-dependent decreases in maximal velocity of shortening (Vmax), maximal developed isometric force (Fm), and the maximal first derivative of Fm (maximal dF/dt). Dose-dependent decreases of these variables of muscle mechanics were augmented in isoflurane-depressed myocardium. At equimolar concentrations, direct myocardial depression was demonstrated in the following order of severity: nifedipine > diltiazem = verapamil > nicardipine. Percent depressions of Vmax, Fm and maximal dF/dt were significantly greater in muscles when calcium entry blockers were combined with 1MAC isoflurane than in muscles of calcium entry blockers alone. These data suggest that the negative inotropic effects of verapamil, diltiazem, nifedipine, and nicardipine were potentiated by isoflurane.