Effects of anipamil on electrocardiogram, plasma creatine kinase, and reperfusion arrhythmias after coronary occlusion in closed-chest rats.
The effect of anipamil pretreatment on ischemic electrocardiogram changes and loss of creatine kinase (CK) after 3 h of left anterior descending coronary artery (LAD) occlusion (group I) and, in a second set of experiments, on reperfusion arrhythmias after 5 min of coronary occlusion (group II) in closed-chest rats was investigated. An LAD occluder was implanted in animals under anaesthesia 8 days before coronary occlusion. Rats in group I were orally treated for 8 days with 6.0 mg/kg anipamil once daily; LAD occlusion was performed 4 h after the last treatment. Group II animals received a single injection of 0.5 or 1.0 mg/kg anipamil intravenously 30 min before coronary occlusion. Oral anipamil significantly reduced CK loss compared with untreated controls. Three hours after occlusion, plasma CK was 99 +/- 37 U/L in the anipamil group compared with 257 +/- 47 U/L in controls. During the first 10 min after occlusion anipamil delayed the increases of the R wave and of the ST segment. In the reperfusion experiments all control rats showed polymorphous ventricular tachycardia (VT) immediately after restoration of coronary flow; 77% degenerated to ventricular fibrillation (VF). After 0.5 mg/kg anipamil i.v. VT was observed in 61% of the rats, VF only in 14%; pretreatment with 1.0 mg/kg totally prevented reperfusion arrhythmias in all animals. We conclude that pretreatment with anipamil reduces the functional and biochemical damage after acute myocardial ischemia and totally prevents reperfusion-induced arrhythmias in closed-chest rats.
Kirchengast
M
M
Department of Cardiovascular Pharmacology, Knoll AG, Ludwigshafen, F.R.G.
Raschack
M
M
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003402:Creatine Kinase / Q000097:blood*; D004562:Electrocardiography; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002121:Calcium Channel Blockers; D011437:Propylamines; C045313:anipamil; D003402:Creatine Kinase