Reduction of ventricular fibrillation during myocardial reperfusion in the dog by pre-treatment with allopurinol

We postulated that ventricular fibrillation (VF) during myocardial reperfusion is in part secondary to cell membrane damage from free oxygen radicals. During ischemia, myocardial xanthine dehydrogenase undergoes a change to xanthine oxygenase. With reperfusion and the reintroduction of molecular oxygen, free oxygen radical generation can occur and lead to membrane damage and electrical instability. To evaluate our hypothesis, we studied the effect of the xanthine oxidase inhibitor allopurinol (ALLO) on reperfusion VF. We analyzed 29 acute open-chest dogs undergoing myocardial reperfusion after a one-hour ischemic period. Group 1 consisted of 18 control dogs; 13 with left anterior descending (LAD) and 5 with left circumflex (LCx) occlusion. Group 2 consisted of 11 dogs (6 with LAD and 5 with LCx occlusion) pretreated with ALLO 50 mg/kg orally for two days and ALLO 50 mg/kg via the left atrium 20 minutes prior to coronary occlusion. All dogs were receiving prophylactic lidocaine during the ischemic and reperfusion periods. Six dogs in Group 1 had VF vs. none in Group 2 (p < 0.05). We conclude that pretreatment with ALLO reduces the incidence of myocardial reperfusion VF in the dog. These findings suggest that oxygen radicals generated by xanthine oxidase play a role in reperfusion VF.