Cardioprotective effect of bepridil on ischemic myocardial damages in dogs.
The cardioprotective effect of bepridil was investigated. Nineteen adult mongrel dogs were divided into 2 groups; in the control group, physiological saline was administered and 25 min later the left anterior descending coronary artery (LAD) was occluded for 2 hr; in the bepridil group, bepridil (1 mg/kg) was administered 25 min before 2 hr LAD occlusion and followed by a constant infusion (1 mg/kg/hr). Blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after occlusion, mitochondria were prepared from both nonischemic and ischemic areas in each group, and their function was measured polarographically. Fractionation of myocardial tissue from both nonischemic and ischemic areas was performed, and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured in each fraction. In the bepridil group, decrease in heart rate was observed without significant changes in blood pressure. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 hr occlusion were observed. Administration of bepridil significantly maintained the mitochondrial function and significantly prevented the leakage of lysosomal enzymes. These results indicate that bepridil might have a cardioprotective effect on ischemic myocardium.
Hanaki
Y
Y
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Hieda
N
N
Taki
K
K
Ozawa
T
T
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D015764:Bepridil; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D011759:Pyrrolidines; D015764:Bepridil; D005966:Glucuronidase; D000118:Acetylglucosaminidase