Thrombolysis in acute experimental myocardial infarction

Lysis of thrombi by intracoronary application of streptokinase has become a new therapeutic approach in patients with acute myocardial infarction. To simulate the clinical situation of myocardial infarction a new experimental model was developed, which was based on a thrombotic coronary occlusion at the site of a high degree stenosis created by a constrictor. In 20 dogs, two ligations 15 mm apart were prepared at the left anterior descending or circumflex coronary artery. After closure of the distal ligation, 2 IU of thrombin was injected through a catheter directly in front of the proximal ligation. The catheter was withdrawn and the proximal ligation was closed. Occlusion time ranged from 1 to 6 hours. At 1, 2, 4 and 6 hours after occlusion, streptokinase was infused for 1 hour (100,000 IU in 200 ml of saline solution) into the left main coronary artery. Hemodynamic variables and coronary blood flow to the ischemic and normal myocardial areas were recorded continuously. Myocardial perfusion was measured six times with tracer microspheres. Reinstatement of blood flow, as well as normalization of myocardial perfusion in the ischemic area, was achieved by streptokinase at 5 minutes after 1 hour of occlusion, 8 minutes after 2 hours, 15 minutes after 4 hours, and 30 minutes after 6 hours; no hyperemic flow occurred. Postmortem staining of infarct size revealed more than 50% of viable myocardium in the perfusion area of the thrombotic vessel even after 6 hours of occlusion. Hemorrhage occurred only after 6 hours of occlusion and was limited to the central area of necrosis in the subendocardial layer. Serious reperfusion arrhythmias occurred only after 1 and 2 hours of occlusion and seemed to be independent of the mode of reperfusion; however, the total number of episodes of ventricular fibrillation after reperfusion was probably decreased compared with that after sudden and hyperemic reflow.