Orally administered benidipine and manidipine prevent ischemia-reperfusion injury in the rat heart.
BACKGROUND
The present study was designed to investigate whether orally administered benidipine and manidipine protect the myocardium from ischemia - reperfusion injury.


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.
Masanori
Sakaguchi
S
Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, Japan. m3813896@msic.med.osaka-cu.ac.jp
Toshihiko
Shibata
S
Koji
Hattori
H
Hidekazu
Hirai
H
Mitsuharu
Hosono
H
Takanobu
Aoyama
A
Takeshi
Ikuta
I
Yasuyuki
Bito
B
Shigefumi
Suehiro
S
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D004095:Dihydropyridines / Q000008:administration & dosage*; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage*; D016277:Ventricular Function, Left / Q000187:drug effects
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D014665:Vasodilator Agents; C061004:benidipine; C054218:manidipine; D003402:Creatine Kinase