The role of histamine in cardiac anaphylaxis; characterization of histaminergic H1-and H2-receptor effects

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Abstract
Histamine is known to act as a direct stimulator. In the heart, two types of histamine receptors are present: H1- and H2-receptors. H2-receptors cause an increase in heart rate and contractility as well as coronary vasodilatation, whereas H1-receptors mediate chronotropic effects and coronary vasoconstriction. During anaphylactic states, histamine is released from cardiac tissue where it is stored in large amounts. The present study was designed to ascertain the role of cardiac histamine release during cardiac anaphylaxis. In guinea pigs, sensitization was produced by intraperitoneal administration of ovalbumin (O). 14 days after sensitization, the effects of an intracoronary infusion of O (1.1×10−8 moles/min) were tested in the isolated perfused heart preparation. The response of the sensitized hearts to O was characterized by a rapid increase in contractile force (dp/dtmax 120% above baseline after 30 s), followed by a decrease reaching a minimum of 30% below bascline after 10 min. Over the same time range, the heart rate first increased (+24%), then decreased, concurrent with the appearance of arrhythmias, before reaching baseline level. Coronary flow decreased (−40% after 1 min) and finally stabilized at a new steady state (−20% below baseline). It is concluded that histamine might be an important mediator of these effects, since in the presence of H2-receptor blockade with cimetidine 96.2×10−7 moles/min), the positive inotropic and chronotropic effects were completely antagonized. Furthermore, a decrease in heart rate and contractility occurred (−25% and −50% after 2 min, respectively). Finally, coronary constriction was intensified and resulted in coronary spasm with flow rates approaching zero after 1 min. On the other hand, additional H1-receptor blockade with dimetinden (2.5×10−9 moles/min) did not antagonize the development of coronary spasm significantly and did not influence the decrease in contractility and the occurrence of bradycardia. The results obtained therefore suggest that besides histamine, other mediators are involved in the development of cardiac anaphylaxis. The cardiodepressant actions of these anaphylactic mediators were revealed by the H2-receptor blockade.

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