title: Infarct salvage with liposomal prostaglandin E1 administered by intravenous bolus immediately before reperfusion in a canine infarction-reperfusion model.
abstract: 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.
  
  
  RESULTS
  Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE1 (2 micrograms/kg), or TLC C-53 (2 micrograms/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 mah be useful in limiting reperfusion injury during treatment of acute myocardial infarction.
authors.affiliation: Division of Cardiology, University of Texas Health Science Center, Houston, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Smalling
authors.forename: S
authors.initials: S
authors.lastname: Feld
authors.forename: N
authors.initials: N
authors.lastname: Ramanna
authors.forename: J
authors.initials: J
authors.lastname: Amirian
authors.forename: P
authors.initials: P
authors.lastname: Felli
authors.forename: W K
authors.initials: WK
authors.lastname: Vaughn
authors.forename: C
authors.initials: C
authors.lastname: Swenson
authors.forename: A
authors.initials: A
authors.lastname: Janoff
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004337:Drug Carriers; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008081:Liposomes; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D000527:Alprostadil