Preservation of ischemic myocardial tissue with an antagonist of vasoconstrictor eicosanoids.

Abstract

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.

• Authors: A M Lefer, S E Burke, I Lepran
• Journal: Canadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 62 Issue 12 Pg. 1487-91 (Dec 1984) ISSN: 0008-4212 [Print] Canada
• PMID: 6241500 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dibenzothiepins
• Receptors, Prostaglandin
• Receptors, Thromboxane
• Thromboxanes
• L 640035
• Creatine Kinase

Topics

• Animals
• Cats
• Coronary Disease (physiopathology)
• Creatine Kinase (blood)
• Dibenzothiepins (pharmacology)
• Electrocardiography
• In Vitro Techniques
• Male
• Platelet Aggregation (drug effects)
• Receptors, Prostaglandin (drug effects)
• Receptors, Thromboxane
• Thromboxanes (antagonists & inhibitors)
• Vasoconstriction (drug effects)