Effects of compound 48/80 on the guinea-pig isolated heart: A comparison with the in vitro cardiac anaphylaxis

The actions of bolus injections of 50 μg of compound 48/80 were analysed upon the isolated heart of the guinea-pig perfused according the Langendorff's method. A first injection produces positive inotropic and chronotropic effects which are rapidly replaced by negative inotropism and a decrease in coronary flow. On successive injections only the decreased flow and contractility are observed. The positive inotropism is blocked by the association of H 1 and H 2 anti-histamines. Tissue histamine is decreased in hearts treated with 48/80. Although the initial effects of 48/80 and cardiac anaphylaxis are very similar, our results show an independence of at least part of the histamine released in the two situations. The results obtained by perfusing the heart at constant flow, indicate that the negative inotropism in consequent to a coronary vasoconstriction. This late action which is also similar to the second phase of the cardiac anaphylaxis might result from the release of endogenous coronary constrictors such as SRS-A, thromboxanes or other compounds.