ENHANCED THROMBOLYSIS, REDUCED CORONARY REOCCLUSION AND LIMITATION OFINFARCT SIZE WITH LIPOSOMAL PROSTAGLANDIN E(1) IN A CANINE THROMBOLYSIS MODEL

Objectives, The purpose of this study was to test the hypothesis that liposomal prostaglandin E(1) (TLC C-53) would result in more rapid thr ombolysis, less reocclusion and smaller infarct size when administered with heparin and streptokinase in a canine thrombolysis model. Backgr ound. In experimental animals, prostaglandin E(1) has been shown to au gment thrombolysis, improve coronary flow and reduce infarct size when infused directly into the left atrium. TLC C-53 is a stable preparati on of prostaglandin E(1) bound by phospholipid microspheres that produ ces fewer adverse hemodynamic effects during intravenous use. Methods. To investigate the effects of TLC C-53 on coronary patency and infarc t salvage, we studied 30 conditioned open chest dogs. After coil induc ed left anterior descending coronary artery occlusion and 1 h of clot maturation, the dogs were randomly assigned to receive a 10-min intrav enous infusion of either TLC C-53 (2 mu g/kg body weight) or placebo. Both groups then received intravenous heparin and streptokinase. Hemod ynamic variables and Doppler coronary flow were monitored, and myocard ial blood flow was determined using radioactive microspheres. Infarct size was assessed with triphenyltetrazolium chloride staining. Results . Thrombolysis time was accelerated from 79 +/- 38 to 47 +/- 9 min (me an +/- SD), and coronary patency was greater (100% vs. 50%) with TLC C -53 than with placebo (p < 0.05). Moreover, for arteries that recanali zed, coronary Doppler flow and myocardial perfusion were more severely impaired with placebo. Infarct size as a percent of the area at risk was higher (p < 0.05) with placebo (51 +/- 15%) than with TLC C-53 (33 +/- 14%). Neutrophil infiltration into ischemic myocardium determined by myeloperoxidase assay was also significantly greater in the placeb o group. Conclusions. TLC C-53 administered intravenously before throm bolytic therapy resulted in a significant acceleration of thrombolysis time, improvement in coronary patency and blood flow during reperfusi on and a reduction in infarct size.