The effect of cibenzoline on myocardial damages in dogs.
The antiarrhythmic and cardioprotective effects of cibenzoline (4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole) were investigated. Nineteen adult mongrel dogs were divided into 2 groups; in the control group, physiological saline (25 ml) was administered, and 20 min after, the left anterior descending coronary artery (LAD) was occluded for 2 h; in the cibenzoline group, cibenzoline (2 mg/kg), was administered 10 min before 2 h LAD occlusion. Blood pressure and appearance of arrhythmias were monitored throughout the experiment. Two h after occlusion, mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions were measured polarographically. Fractionation of myocardial tissue from both ischemic and non-ischemic areas was performed, and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured in each fraction. Administration of cibenzoline significantly reduced the appearance of ventricular arrhythmias in association with ischemia. Cibenzoline did not change significantly blood pressure and heart rate. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 h occlusion were observed. Administration of cibenzoline maintained significantly mitochondrial function and prevented significantly leakage of lysosomal enzymes. These results indicated that cibenzoline has a cardioprotective as well as an antiarrhythmic effect on ischemic myocardium.
Department of Anesthesiology, Faculty of Medicine, University of Nagoya, Japan.
K
K
Taki
S
S
Sugiyama
N
N
Hieda
Y
Y
Hanaki
T
T
Sano
Y
Y
Shimada
T
T
Ozawa
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D005966:Glucuronidase; C032151:cifenline