Protective action of methylprednisolone on the myocardium during experimental myocardial ischemia in the cat.

Cats subjected to coronary artery occlusion were used to study the effect of methylprednisolone on the release of lysosomal acid hydrolases and creatine phosphokinase (CPK) from ischemic myocardial tissue. Plasma CPK activity was increased significantly 2 hours after occlusion and increased eightfold 5 hours after ligation in vehicle-treated cats. Intravenous administration of methylprednisolone (30 mg/kg) 30 minutes before or 60 minutes after occlusion significantly limited the increases in plasma CPK activity to values only slightly greater than those observed in sham-operated cats. Plasma activities of the lysosomal hydrolases, /3-glucuronidase and cathepsin D, were comparable in all groups of cats and did not change during the 5-hour observation period. Nevertheless, cathepsin D and /3-glucuronidase activities were reduced 41% and 33%, respectively, in the ischemic portion of the myocardium of untreated cats subjected to coronary artery ligation. The CPK activity of the ischemic myocardium was reduced 43% in these cats. Preor posttreatment of cats with methylprednisolone prevented the decline in CPK and lysosomal hydrolase activity of ischemic myocardium. These data indicate that lysosomal disruption is a consequence of myocardial ischemia and that preor posttreatment with methylprednisolone prevents the leakage of myocardial lysosomal and cellular enzymes. Moreover, the methylprednisolone-induced stabilization of myocardial membranes appears to be related to the ability of glucocorticoid to limit infarct size following myocardial ischemia.