The influence of the time interval between coronary artery occlusion and the administration of hyaluronidase on salvage of ischemic myocardium in dogs

The purpose of this study was to determine the time interval following coronary artery occlusion during which the administration of hyaluronidase exerts a significant protective effect on injured myocardium. Forty eight open chest dogs with coronary artery occlusion were studied. Fourteen were untreated (controls). Hyaluronidase (500 NF units/kg, iv) was administered 20 minutes (12 dogs), 3 hours (8 dogs), 6 hours (8 dogs), or 9 hours (6 dogs) after occlusion. Epicardial electrograms, recorded from 10 to 16 sites on the anterior surface of the left ventricle before, 15 minutes after, and 24 hours after coronary occlusion were analyzed for S-T segment elevation and changes in QRS morphology. Transmural specimens, excised 24 hours after occlusion from the sites at which the electrograms were recorded, were analyzed for creatine phosphokinase (CPK) activity and histological appearance. In all five groups, myocardial CPK depression, histological evidence of the extent of necrosis, and changes in QRS configuration correlated well with one another. In the controls, S-T segment elevation 15 minutes after occlusion (ST₁₅(m)) correlated well with myocardial CPK depression, histological extent of necrosis, and changes in the QRS complex 24 hours later. When hyaluronidase was given 20 minutes, 3 hours, or 6 hours after coronary occlusion, myocardial salvage was reflected in significantly less myocardial CPK depression for any given ST₁₅(m), less histological evidence of infarction, and less extensive changes in QRS configuration than in the untreated dogs, although there was a progressive reduction in tissue salvage as the time interval between occlusion and drug administration lengthened. Hyaluronidase administered 9 hours after occlusion had no demonstrable effect on the development of myocardial necrosis, suggesting that ischemic injury is totally irreversible by this time.