Protective effect of methionine in the ischemia-reperfusion cardiac injury in the canine model

Abstract

Oxygen free radicals (OFRs) derived from activated polymorphonuclear (PMN) leukocytes have been implicated in the ischemia-reperfusion cardiac injury. Hypochlorous acid (HOCl) is produced by activated PMN leukocytes and can damage tissue directly or through formation of hydroxyl radicals. We therefore investigated the effects of methionine (a quencher of HOCl) on cardiac function and cardiac contractility; oxygen-free, radical-producing activity of PMN leukocytes (PMN-CL); serum malondialdehyde (MDA); activity of creatine kinase (CK) and MB fraction of CK (CK-MB); blood lactate, and pH and infarct size after 3 hours of reperfusion following 1.5 hours of occlusion of the left circumflex coronary artery (LCX) in anesthetized dogs. The dogs were divided into three groups: Group I, complete ligation of LCX for 4.5 hours; Group II, ligation of LCX for 1.5 hours followed by 3 hours of reperfusion; Group III, similar to Group II but received methionine 60 mg/kg, i.v. 10 minutes before ligation, 10 minutes before reperfusion, and 60 minutes after reperfusion. Measurements of hemodynamic parameters and collection of blood samples for biochemical parameters were made at various intervals. In general, myocardial contractility was unaltered whereas cardiac function decreased to a similar extent in the three groups. The area at risk was similar and infarct size was greater in Groups II and III, but both were greater than in Group I. The size in Group III was smaller than in Group II. CK and CK-MB activity increased in all groups but more in Groups II and III than in Group I. The increases were smaller in Group III than in Group II. PMN-CL activity increased significantly in Group II but remained unchanged in Groups I and III. Serum MDA remained unchanged. Changes in blood lactate and pH were similar in the three groups. These results suggest that (1) the area at risk in unperfused ischemic myocardium is smaller than in perfused ischemic myocardium; (2) reperfusion produced greater myocardial necrosis as compared with unperfused ischemic myocardium; (3) methionine is very effective in preventing ischemia-reperfusion-induced myocardial necrosis.