Enhanced thrombolysis, reduced coronary reocclusion and limitation of infarct size with liposomal prostaglandin E1 in a canine thrombolysis model

Abstract

Objectives: The purpose of this study was to test the hypothesis that liposomal prostaglandin E1 (TLC C-53) would result in more rapid thrombolysis, less reocclusion and smaller infarct size when administered with heparin and streptokinase in a canine thrombolysis model.

Background: In experimental animals, prostaglandin E1 has been shown to augment thrombolysis, improve coronary flow and reduce infarct size when infused directly into the left atrium. TLC C-53 is a stable preparation of prostaglandin E1 bound by phospholipid microspheres that produces fewer adverse hemodynamic effects during intravenous use.

Methods: To investigate the effects of TLC C-53 on coronary patency and infarct salvage, we studied 30 conditioned open chest dogs. After coil-induced left anterior descending coronary artery occlusion and 1 h of clot maturation, the dogs were randomly assigned to receive a 10-min intravenous infusion of either TLC C-53 (2 micrograms/kg body weight) or placebo. Both groups then received intravenous heparin and streptokinase. Hemodynamic variables and Doppler coronary flow were monitored, and myocardial 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 (mean +/- SD), and coronary patency was greater (100% vs. 50%) with TLC C-53 than with placebo (p < 0.05). Moreover, for arteries that recanalized, 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 placebo group.

Conclusions: TLC C-53 administered intravenously before thrombolytic therapy resulted in a significant acceleration of thrombolysis time, improvement in coronary patency and blood flow during reperfusion and a reduction in infarct size.