The Antioxidant, N-(2-mercaptopropionyl)-glycine (MPG), Does Not Reduce Myocardial Infarct Size in an Acute Canine Model of Myocardial Ischemia and Reperfusion.
Oxygen radical generation can be measured when blood flow is restored to previously ischemic tissue. Although several studies have suggested oxygen radicals contribute to lethal injury of myocardium after ischemia, other studies have failed to confirm this implication. Antioxidants, such as N-(2-mercaptoptopionyl)-glycine (MPG) and superoxide dismutase, have had inconsistent effects on lethal myocardial injury in animal models of ischemia and reperfusion. Many variables influence lethal myocardial injury in these models: time of ischemia, time of reperfusion, dose of antioxidant, myocardial oxygen demand, area at risk, collateral blood flow, and body core temperature. The purpose of this study is to test the effects of infusion of MPG on lethal reperfusion injury in a canine model of ischemia and reperfusion with these variables tightly controlled. The left anterior descending coronary artery of anesthetized dogs was ligated for 90 minutes and reperfused for 4 hours. MPG was infused (100 mg/kg/h) 15 minutes before the end of ischemia and throughout reperfusion. Core body temperature was closely monitored, and infarct size was adjusted to transmural myocardial blood flow during ischemia. MPG had no effect on infarct size or infarct size adjusted for changes in collateral blood flow. These data reinforce a general difficulty in demonstrating the effects of antioxidant therapies on lethal injury, even when closely monitoring covariates known to impact infarct size.
Venturini
CM
Cardiovascular Diseases Research Department, G. Searle & Co., Monsanto Company, St. Louis, Missouri.
Flickinger
AG
Womack
CR
Smith
ME
McMahon
EG