Does tissue-type plasminogen activator have direct beneficial effects on the myocardium independent of its ability to lyse intracoronary thrombi?

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Abstract
Tissue-type plasminogen activator (t-PA) is a widely used thrombolytic agent for treating acute myocardial infarction. Some previous studies suggest that t-PA benefits the heart independently of lysing coronary artery thrombi. The purpose of this study was to determine whether t-PA directly affects infarct size independently of lysing coronary thrombi, affects the no-reflow phenomenon, and exacerbates intramyocardial hemorrhage. We used a canine model of 2 hours of occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. t-PA was administered 30 minutes after occlusion and was continued for 2 hours. Myocardial infarct size as a percentage of the risk zone was similar between saline (28 +/- 8%) and t-PA (35 +/- 9%) groups in a low-dose study and between saline (46 +/- 12%) and t-PA (44 +/- 12%) groups in a high-dose study. t-PA did not improve no-reflow. Intramyocardial hemoglobin level within the infarct was similar between saline (16 micrograms/mg) and high-dose t-PA ...