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(Circulation. 1995;92:935-943.)
© 1995 American Heart Association, Inc.

Articles

Infarct Salvage With Liposomal Prostaglandin E₁ Administered by Intravenous Bolus Immediately Before Reperfusion in a Canine Infarction-Reperfusion Model

Richard W. Smalling, MD, PhD; Steven Feld, MD; Nagendra Ramanna, MD; James Amirian, BS; Patty Felli, BS; William K. Vaughn, PhD; Christine Swenson, PhD; Andrew Janoff, PhD

From the Division of Cardiology, University of Texas Health Science Center, Houston; the Texas Heart Institute, Houston (W.K.V.); and the Liposome Co, Inc, Princeton, NJ (C.S., A.J.).

Correspondence to Richard W. Smalling, MD, PhD, Professor of Medicine, University of Texas Medical School, MSB 1.246, 6431 Fannin, Houston, TX 77030.

Background Prostaglandin E₁ (PGE₁) inhibits leukocyte and platelet function and reduces infarct size during left atrial infusion. Intravenous liposomal PGE₁ (TLC C-53) accelerates thrombolysis and prevents reocclusion in canine coronary thrombosis. We tested the hypothesis that intravenous TLC C-53 would attenuate reperfusion injury in a canine infarction-reperfusion model.

Methods and Results Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE₁ (2 µg/kg), or TLC C-53 (2 µg/kg PGE₁) after 2 hours of left anterior descending (LAD) occlusion just before reperfusion. Hemodynamic assessment, regional myocardial blood flow determination with radioactive microspheres, myocardial leukocyte infiltration by myeloperoxidase assay, and estimation of infarct size using triphenyl tetrazolium chloride staining were performed. Regional fractional shortening was measured with sonomicrometer crystals implanted in the midmyocardium. Infarct size as a percentage of the risk region was significantly reduced (P<.05) with TLC C-53 (37.9±17.4%) compared with PGE₁ (56.7±13.9%) or placebo (58.0±9.9%) infusion. Infarct salvage with TLC C-53 was independent of collateral blood flow by ANCOVA. There was a dramatic reduction in myeloperoxidase activity in the infarct, risk, and border regions of dogs treated with TLC C-53 compared with placebo. Enzyme activity was also significantly reduced (P<.05) in the infarct zone with TLC C-53 (0.11±0.1 U/100 mg) treatment compared with PGE₁ (0.38±0.3 U/100 mg). No significant differences in regional myocardial blood flow or myocardial function among treatment groups were identified, although there was a trend toward improved function in the TLC C-53 dogs.

Conclusions Bolus intravenous administration of TLC C-53 immediately before reperfusion 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.

Key Words: liposomes • prostaglandins • reperfusion

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