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Published on: June 25, 2012

Leukotriene D4-induced vasoconstriction of coronary arteries in anaesthetized dogs

V B Fiedler, M Mardin, T S Abram

    European Heart Journal
    |March 1, 1984
    PubMed

    Insights

    Leukotriene D4 (LTD4) constricts coronary arteries in dogs, reducing blood flow and increasing resistance. This effect is independent of cyclooxygenase and lipoxygenase pathways, suggesting LTD4

    Area of Science:

    • Cardiovascular Physiology
    • Pharmacology

    Background:

    • Leukotriene D4 (LTD4) is implicated in inflammatory and allergic responses.
    • Its role in direct coronary artery constriction and its underlying mechanisms require further elucidation.

    Purpose of the Study:

    • To investigate the direct effects of intracoronary leukotriene D4 (LTD4) on coronary artery diameter, blood flow, and resistance in a canine model.
    • To determine if LTD4-induced coronary effects are mediated by cyclooxygenase or lipoxygenase metabolites.

    Main Methods:

    • Pentobarbital-anesthetized dogs were administered intracoronary LTD4 (0.1-10 µg/kg).
    • Hemodynamic variables including coronary artery flow, diameter, resistance, heart rate, and ventricular pressures were measured.
    • Electrocardiography (ECG) was used to assess myocardial ischemia.
    • Experiments were repeated after inhibition of cyclooxygenase (indomethacin) and lipoxygenase (nafazatrom) enzymes.

    Main Results:

    • Intracoronary LTD4 caused a dose-dependent reduction in coronary artery diameter (up to 12%) and coronary blood flow (up to 100%).
    • LTD4 administration led to a significant increase in small and total coronary resistance (33-232% and 50-500%, respectively).
    • Myocardial ischemia was indicated by ECG changes during LTD4-induced flow cessation.
    • Inhibition of cyclooxygenase and lipoxygenase enzymes did not alter the effects of LTD4.

    Conclusions:

    • Intracoronary LTD4 administration directly constricts coronary arteries in dogs, primarily affecting large conductive vessels.
    • The coronary constrictive effects of LTD4 are independent of cyclooxygenase and other lipoxygenase metabolites.
    • LTD4 may play a role in cardiac dysfunction associated with coronary artery disease and vasospasm.

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