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 contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. 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 microM 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 microM 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 heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.
Ozturk
T
T
Department of Izmir Chest Diseases and Surgery Hospital, Izmir Goägüs Hastaliklari ve Cerrahisi Merkezi, Tepecik Izmir, 35110, Turkey.
Tuncok
Y
Y
Kalkan
S
S
Guven
H
H
Aran
G
G
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D018686:Anesthetics, Intravenous; D018757:GABA Modulators; D005442:Flumazenil; D008874:Midazolam