Role of tissue factor-mediated coagulation in ischemia/ reperfusion-induced injury of Langendorf-perfused rabbit hearts

Lisa Armaganian, Galen Kam, Paul R. Eisenberg, Kenneth B. Schechtman, Dana R. Abendschein

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Production of oxygen free radicals, and activation of neutrophils and plasma complement contribute to myocardial reperfusion injury, but the role of coagulation has not been assessed. Objective: To characterize tissue-factor-mediated generation of thrombin and its association with tissue injury during reperfusion from normothermic ischemia of isolated, Langendorf-perfused rabbit hearts. Methods: Activation of coagulation was assessed by addition of 12% rabbit plasma and human fibrinogen to Krebs - Henseleit-buffer perfusate with measurement of levels of human fibrinopeptide A (hFPA) in the heart effluent as an index of thrombin-mediated formation of fibrin. Results: Concentrations of hFPA in the effluent were minimal during non-ischemic perfusion (5 ± 5 ng/ml, n=6) and during 50 min of ischemia (13 ± 3 ng/ml, n=6), but increased markedly during the first 20 min of reperfusion (to 41 ± 29 ng/ml, P=0.03 versus before reperfusion). Addition to the perfusate of 10 μg/ml recombinant human tissue-factor-pathway inhibitor, the physiologic inhibitor of tissue-factor-mediated coagulation, abolished increases in the level of hFPA after reperfusion. However, indexes of myocardial injury manifested during reperfusion, including decrease in recovery of left ventricular pressure developed, increase in left ventricular end-diastolic pressure, and increase in activity of creatine kinase in the head effluent, were not improved by anticoagulation with recombinant human tissue-factor-pathway inhibitor. Conclusion: Our results do not support the hypothesis that coagulation plays a major role in ischemia/reperfusion injury of Langendorf-perfused rabbit hearts. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)481-487
Number of pages7
JournalCoronary Artery Disease
Volume11
Issue number6
DOIs
StatePublished - Sep 12 2000

Keywords

  • Coagulation
  • Myocardial ischemia/reperfusion injury
  • Tissue factor
  • Tissue-factor-pathway inhibitor

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