Drug effects on the ischemia- and reperfusion-induced arrhythmias in the conscious rats

A simple model of coronary occlusion and reperfusion in conscious rat was used to test the effects of various drugs on the arrhythmias. Blood pressure and ECG were monitored on a Grass polygraph. Intravenous infusion of test agents started before coronary occlusion and continued through the periods of occlusion and reperfusion. The free radical scavengers (allopurinol 12.3 mg/kg, mannitol 33.0 mg/kg, N-2-mercapto-propionyl glycine 8.6 mg/kg and adenosine 10.0 mg/kg), class 1-4 antiarrhythmic drugs (lidocaine 10.2 mg/kg, quinidine 12.3 mg/kg, propranolol 4.9 mg/kg, amiodarone 5.6 mg/kg and verapamil 1.1 mg/kg), aspirin 24.5 mg/kg and benadryl 3.7 mg/kg reduced the incidence of ventricular fibrillation and shortened the duration of arrhythmias during occlusion and reperfusion. Cimetidine 6.9 mg/kg was ineffective to exert the antiarrhythmic action. These results implicate that multiple factors, such as ionic channels (Na, K and Ca), free radicals, arachidonate metabolites and histamine release may play significant roles in genesis of arrhythmias during myocardial ischemia and reperfusion.