Recombinant tissue-type plasminogen activator ameliorates ischemic derangements induced by thrombotic occlusion in closed chest anesthetized dogs

Effects of thrombotic coronary occlusion followed by thrombolytic reperfusion with recombinant tissue-type plasminogen activator (rt-PA) on infarct size and left ventricular function were studied in anesthetized closed chest dogs. After thrombotic occlusion of the left anterior descending coronary artery was produced by a copper coil technique, 74 dogs were randomly allotted to three groups; dogs treated with rt-PA at 90 min (n = 23) (group I) and at 180 min (n = 25) (group II) of the thrombotic occlusion, and 26 dogs treated with saline solution (permanent thrombotic occlusion, group III). The loading dose of intravenous rt-PA was 8,160 IU/kg body weight per min at the initial 60 min and the maintenance dose was 2,450 IU/kg per min continuously infused far 24 h. Thrombolytic recanalization was achieved at 15 ± 4 and 18 ±6 min after rt-PA infusion in groups I and II, respectively. Infarct size and area at risk were determined by triphenyltetrazolium chloride staining and postmortem angiography; infarct size/area at risk ratio was 10 ± 3% (n = 10), 33 ± 7% (n = 9) and 63 ± 3% (n = 10) in groups I, II and III, respectively (difference significant among groups). To examine whether infarct size and left ventricular function after thrombolytic reperfusion differ from those after mechanical reperfusion, 39 other dogs (group IV) underwent mechanical coronary occlusion for 106 ± 1 min (occlusion period comparable with that of group I) and reperfusion using a balloon catheter. Infarct size/area at risk ratio in group IV was 27 ± 5% (n = 12), which was smaller than that in group III (p < 0.01) and larger than that in group I (p < 0.05). The abnormally contracting area within the left ventricle in groups I and IV was 33 ± 5% and 38 ± 3%, respectively, at 90 min, and 9 ± 4% and 33 ± 4% (p < 0.01) at 24 h of coronary occlusion. The results suggest that thrombolylic reperfusion with timely administration of rt-PA had more beneficial effects on infarct size and left ventricular function than did mechanical occlusion and reperfusion.