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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 degrees 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.