INFARCT SALVAGE WITH LIPOSOMAL PROSTAGLANDIN E(1) ADMINISTERED BY INTRAVENOUS BOLUS IMMEDIATELY BEFORE REPERFUSION IN A CANINE INFARCTION-REPERFUSION MODEL

Background Prostaglandin E(1) (PGE(1)) inhibits leukocyte and platelet function and reduces infarct size during left atrial infusion. Intrav enous liposomal PGE(1) (TLC C-53) accelerates thrombolysis and prevent s reocclusion in canine coronary thrombosis. We tested the hypothesis that intravenous TLC C-53 would attenuate reperfusion injury in a cani ne infarction-reperfusion model. Methods and Results Twenty-one open-c hest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE(1) (2 mu g/kg), or TLC C-53 (2 mu g/kg PGE(1)) after 2 hours of left anterior descending (LAD ) occlusion just before reperfusion. Hemodynamic assessment, regional myocardial blood flow determination with radioactive microspheres, myo cardial leukocyte infiltration by myeloperoxidase assay, and estimatio n of infarct size using triphenyl tetrazolium chloride staining were p erformed. Regional fractional shortening was measured with sonomicrome ter crystals implanted in the midmyo-cardium. Infarct size as a percen tage of the risk region was significantly reduced (P<.05) with TLC C-5 3 (37.9+/-17.4%) compared with PGE(1) (56.7+/-13.9%) or placebo (58.0/-9.9%) infusion. Infarct salvage with TLC C-53 was independent of col lateral blood flow by ANCOVA. There was a dramatic reduction in myelop eroxidase activity in the infarct, risk, and border regions of dogs tr eated with TLC C-53 compared with placebo. Enzyme activity was also si gnificantly reduced (P<.05) in the infarct zone with TLC C-53 (0.11+/- 0.1 U/100 mg) treatment compared with PGE(1) (0.38+/-0.3 U/100 mg). No significant differences in regional myocardial blood flow or myocardi al function among treatment groups were identified, although there was a trend toward improved function in the TLC C-53 dogs. Conclusions Bo lus intravenous administration of TLC C-53 immediately before reperfus ion results in reduced leukocyte infiltration and substantial infarct salvage. TLC C-53 may be useful in limiting reperfusion injury during treatment of acute myocardial infarction.