Orally Administered Benidipine and Manidipine Prevent Ischemia - Reperfusion Injury in the Rat Heart

Abstract

Background The present study was designed to investigate whether orally administered benidipine and manidipine protect the myocardium from ischemia - reperfusion injury. Methods and Results Each drug (1, 3 or 10 mg/kg) was administered orally once daily for 1 week. The isolated rat heart model (Langendorff perfusion) was used, and each heart was subjected to global ischemia at 37°C for 40 min followed by reperfusion. Post-ischemic recovery of left ventricular (LV) function (measured as developed pressure (LVDP), dP/dt max and end-diastolic pressure) was compared with a control group. Creatine kinase (CK) leakage was also measured. Post-ischemic recovery of LVDP and LV dP/dt max were significantly increased by 3 mg/kg benidipine (LVDP: 87.5±10.1 vs 64.6±11.9%; LV dP/dt max: 97.8±10.4 vs 70.2±15.7%; p<0.05). CK leakage was significantly lower than in the control group (39.4±7.5 vs 61.1 ±9.8 IU per 15 min per kg; p<0.05). Manidipine produced significant recoveries in LVDP and dP/dt max at a dose of 1 mg/kg (LVDP: 93.7±16.5% vs 53.4±9.5%; dP/dt max: 104.2±21.9% vs 55.5±15.5%; p<0.05). CK leakage was also significantly reduced at the same dose (50.0±18.3 vs 80.1±14.0 IU per 15 min per kg; p<0.05). Conclusions Orally administered benidipine and manidipine exerted significant cardioprotective effects against ischemia - reperfusion injury. (Circ J 2004; 68: 241 - 246)