Midazolams cardiac depressant effects and their lack of reversal by flumazenil in isolated rabbit hearts

Midazolam is known to cause a dose-dependent increase and decrease in the c ontractile force of the myocardium. Whether flumazenil can reverse these ef fects of midazolam remains unclear. In this study, we determined the cardia c effects of midazolam and the counter effect of flumazenil on midazolam-in duced myocardial depression in isolated rabbit hearts. Rabbit hearts were i solated and perfused using the Langendorff technique, and left ventricle pr essure and heart rate were measured by a pressure transducer in the left ve ntricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 mu M midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0 .01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 mu M midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and hear t rate of isolated rabbit hearts in a concentration-dependent manner. The f ailure of flumazenil to reverse these effects suggest that this cardiac dep ressant effect of midazolam is not mediated through peripheral benzodiazepi ne-receptors. (C) 1999 Academic Press.