Flumazenil does not antagonize the cardiac effects of midazolam in the isolated rat heart-lung preparation

We examined the effects of midazolam and flumazenil on cardiac function and metabolism in the isolated rat heart-lung preparation. Wistar rats were divided into five groups (each group:n=8) as follows: (1) control (saline); (2) flumazenil (1.3×10⁻⁵M); (3) flumazenil (10⁻⁴M); (4) midazolam (60μg·ml⁻¹); and (5) midazolam (60μg·ml⁻¹) and flumazenil (1.3×10⁻⁵M). Systolic blood pressure and calculated left ventricular dP/dt maximum in the midazolam or midazolam conbined with flumazenil groups increased significantly in comparison with those in the control group. Heart rate in the midazolam group was lower than that in the control group. However, in the flumazenil group, there were no effects on the hemodynamics. There were no significant differences in the myocardial tissue concentration of ATP, lactate, and glycogen in all groups. In this study, midazolam decreased heart rate; however, flumazenil had no effect on the heart, nor did it antagonize the cardiac effects of midazolam. These results suggest that flumazenil has no effect on the peripheraltype benzodiazepine receptor of the myocardium.