Control of Oxygen Cytotoxicity With Allopurinol and Superoxide Dismutase: A Canine Model of Global Myocardial Ischemia-Reperfusion Injury

Abstract

The purpose of this study was to assess the effects of acute pharmacological interventions on the ischemia-reperfusion damage in a canine model of hypothermic global myocardial ischemia. Three experimental groups each consisting of seven animals were subjected to 2 h of global ischemia followed by 1 h of reperfusion. Group A (control) used Tyers' isoosmolar potassium cardioplegia solution; group B received allopurinol (40 mg/kg), 95% intravenously (IV) systemically with 5% added to the final infusion of Tyers' solution. In group C, superoxide dismutase (6.5 mg/kg) was used, one third of the total dose in the final delivery of the Tyers' cardioplegia solution and two thirds IV during the initial 5 min of reperfusion. In all three groups, myocardial temperature was maintained between 15 and 19°C. Methods of evaluation included hemodynamic and echocardiographic parameters of ventricular function. Assessment was performed at three time periods: pre-cardiopulmonary bypass (control), 60 min postreperfusion and immediately post-volume loading (at 2 h after cardiopulmonary bypass). No significant deterioration of myocardial function was observed in either of the experimental groups after the use of these preservation techniques. Comparison of regression slopes based on analysis of covariance for myocardial performance, systolic function, and diastolic compliance did not demonstrate any significant differences between the groups. Two hours of global ischemia was not sufficient to cause measurable damage to the myocardium on the basis of which the pharmacological intervention with allopurinol and superoxide dismutase could be evaluated. The controversy surrounding the use of allopurinol and superoxide dismutase is discussed with the findings of this experimental protocol and is brought up for scientific dialogue.