REDUCTION OF CANINE INFARCT SIZE BY BOLUS INTRAVENOUS ADMINISTRATION OF LIPOSOMAL PROSTAGLANDIN E(1) - COMPARISON WITH CONTROL, PLACEBO LIPOSOMES, AND CONTINUOUS INTRAVENOUS-INFUSION OF PROSTAGLANDIN E(1)

Prostaglandin E(1) (PGE(1)) reduces experimental infarct size when adm inistered by prolonged low-dose left atrial infusion during coronary o cclusion. Liposomal delivery of PGE(1) may enhance biologic activity a nd limit adverse hemodynamic effects. The purpose of this study was to test the hypothesis that intravenous bolus administration of liposoma l PGE(1) (TLC C-53, The Liposome Company, Princeton, N.J.) during coro nary occlusion would result in myocardial salvage. We compared TLC C-5 3 (0.5 mu g/kg intravenous bolus at 10 and 100 min of occlusion of the left anterior descending coronary artery [LAD]), free PGE(1) (0.1 mu g/kg/min infused 10 min after LAD occlusion until reperfusion), placeb o liposomes, and control (n = 7 for each group) in an open-chest canin e model of 2 hours of LAD occlusion and reperfusion. Infarct size as a percentage of risk area (mean +/- SD) in the control group (58.4% +/- 20.0%) was similar to that in animals given placebo liposomes (53.1% +/- 12.6%) but was significantly reduced in the groups given TLC C-53 (33.5% +/- 9.2%; p < 0.01) or free PGE(1) (37.2% +/- 4.8%; p < 0.05) g roups. Infarct salvage was significant (p < 0.05) for the TLC C-53- an d PGE(1)-treated dogs compared with the control dogs, independent of c ollateral blood flow by analysis of covariance. Moreover, the ischemic -zone blood flow during reperfusion was significantly higher in the TL C C-53 group compared with the control group or the group receiving fr ee PGE(1). Neutrophil infiltration of ischemic myocardium was signific antly inhibited by TLC C-53 as determined by myeloperoxidase assay. Un like free PGE(1), TLC C-53 did not cause significant tachycardia or hy potension during therapy. In conclusion, TLC C-53 administered intrave nously during coronary occlusion significantly reduced infarct size, l imited neutrophil infiltration, and improved myocardial blood flow dur ing reperfusion without adverse hemodynamic consequences.