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Effects of Anipamil on Electrocardiogram, Plasma Creatine Kinase, and Reperfusion Arrhythmias After Coronary Occlusion in Closed‐Chest Rats

The effect of anipamil pretreatment on is-chemic 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.