THROMBOXANE AND PROSTACYCLIN RELEASE DURING CARDIAC IMMEDIATE HYPERSENSITIVITY REACTIONS INVITRO

Abstract

Cardiac immediate hypersensitivity reactions in vitro are characterized by tachycardia, arrhythmias and coronary constriction. Whereas endogenous cardiac histamine release is responsible for the generation of arrhythmias, metabolites of arachidonic acid mediate the fall in coronary flow. It was shown that antigenic challenge of sensitized guinea-pig hearts results in the release into the coronary effluent of immunoreactive thromboxane [Tx] B2, 6-keto prostaglandin (PG) F1.alpha. and PGF2.alpha.. Tx B2 was the predominant metabolite generated. After the administration of histamine (1-100 .mu.g) or a partially purified preparation of slow-reacting substance of anaphylaxis [SRSA] (5-100 U) to the sensitized heart there was no detectable release of Tx B2 into the coronary effluent. After the administration of sodium arachidonate (3 .times. 10-6 M) to the sensitized heart 40 min after antigenic challenge, there was a predominant release of 6-keto PGF1.alpha. into the coronary effluent. Pretreatment of sensitized hearts with aspirin (5.5 .times. 10-5 M), indomethacin (1.4 .times. 10-5 M) or 1-(2-isopropylphenyl)imidazole (5.4 .times. 10-5 M) resulted in inhibition of antigen-induced Tx B2 release and coronary vasoconstriction. These results suggest that during immediate hypersensitivity reactions, the coronary vasculature may be predisposed to ischemic and thrombotic episodes as a result of Tx release. Tx formation occurs independently of the actions of histamine and SRSA and, since it is not generated preferentially by the coronary circulation of the sensitized heart in response to arachidonate infusion, it is plausible to suggest that it is of mast cell origin.