Reduction of canine infarct size by bolus intravenous administration of liposomal prostaglandin E1 : Comparison with control, placebo liposomes, and continuous intravenous infusion of prostaglandin E1

Prostaglandin E1 (PGE1) reduces experimental infarct size when administered by prolonged low-dose left atrial infusion during coronary occlusion. Liposomal delivery of PGE1 may enhance biologic activity and limit adverse hemodynamic effects. The purpose of this study was to test the hypothesis that intravenous bolus administration of liposomal PGE1 (TLC C-53, The Liposome Company, Princeton, N.J.) during coronary occlusion would result in myocardial salvage. We compared TLC C-53 (0.5 microgram/kg intravenous bolus at 10 and 100 min of occlusion of the left anterior descending coronary artery [LAD]), free PGE1 (0.1 microgram/kg/min infused 10 min after LAD occlusion until reperfusion), placebo liposomes, and control (n = 7 for each group) in an open-chest canine 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 PGE1 (37.2% +/- 4.8%; p < 0.05) groups. Infarct salvage was significant (p < 0.05) for the TLC C-53-and PGE1-treated dogs compared with the control dogs, independent of collateral blood flow by analysis of covariance. Moreover, the ischemic-zone blood flow during reperfusion was significantly higher in the TLC C-53 group compared with the control group or the group receiving free PGE1. Neutrophil infiltration of ischemic myocardium was significantly inhibited by TLC C-53 as determined by myeloperoxidase assay. Unlike free PGE1, TLC C-53 did not cause significant tachycardia or hypotension during therapy. In conclusion, TLC C-53 administered intravenously during coronary occlusion significantly reduced infarct size, limited neutrophil infiltration, and improved myocardial blood flow during reperfusion without adverse hemodynamic consequences.