Preservation of ischemic myocardial tissue with an antagonist of vasoconstrictor eicosanoids

A. M. Lefer, S. E. Burke, I. Lepran

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A new antagonist of the vasoconstrictor eicosanoids, L-640,035, was studied in a standardized model of myocardial ischemia (MI) in anesthetized cats. This eicosanoid antagonist was not found to exert any overt hemodynamic action in cats subjected to a sham myocardial ischemia protocol. However, the antagonist markedly reduced the S-T segment of the electrocardiogram when administered 30 min after permanent occlusion of the left coronary artery. Moreover, circulating activities of the marker enzyme creatine kinase (CK) were markedly attenuated by L-640,035 3-5 h after the onset of MI. This was verified by cardiac biopsies 5 h post-MI since myocardial CK activities decreased much less in treated MI cats than in MI cats receiving only the vehicle for L-640,035 (i.e., ethanol). The active metabolite of the antagonist in biological fluids (i.e., L-636,499) markedly antagonized the vasoconstrictor actions of endoperoxide and thromboxane analogs, but not of noneicosanoids in isolated perfused coronary arteries.

Original languageEnglish
Pages (from-to)1487-1491
Number of pages5
JournalCanadian journal of physiology and pharmacology
Issue number12
Publication statusPublished - Jan 1 1984


ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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