Myocardial tissue salvage by coronary thrombolysis with rt-PA: Absence of occlusion/reperfusion injury

Abstract

The effect of recombinant tissue-type plasminogen activator (rt-PA) on myocardial infarct size was studied in a coronary thrombosis model in open-chested, anaesthetised beagle dogs. Myocardial ischaemia was produced by localised thrombosis via endothelial injury and instillation of thrombin and fresh blood into the left anterior descending coronary artery (LAD). Myocardial infarct size and the area at risk were determined histochemically after 24 h of reperfusion by ex vivo staining of the LAD bed with 1.5% triphenyltetrazolium chloride (TTC). In non-reperfused animals the persistance of a coronary thrombus resulted in 50.7 ± 5.0% of the area at risk developing an infarct. Intravenous administration of rt-PA at a rate of 12 500 IU/kg/min delivered for 60 min resulted in recanalisation of the thrombosed artery within 16.1 ± 4.1 min in animals in which the thrombus was in place for 75 min and within 19.0 ± 2.8 min after 165 min of stable thrombosis. Lysis of the coronary thrombus and subsequent reperfusion was not accompanied by reactive hyperaemia nor ventricular arrhythmias. Infarct size was reduced to 1.5 ± 1.2% and 6.3 ± 4.1% of the area at risk in the animals whose coronary thrombi were lysed with rt-PA after 1.5 and 3 h of ischaemia, respectively. In contrast, mechanical reperfusion after 1.5 h of ischaemia induced by ligation resulted in an infarct of 35.1 ± 4.5% of the area at risk. These results suggest that rt-PA has an additional cardioprotective effect independent of lysis of the thrombosed coronary artery.