Cardiac dysfunction caused by purified human C3a anaphylatoxin.
The purpose of this investigation was to define the cardiac effects of complement-derived C3a anaphylatoxin, in view of the possibility that cardiac dysfunction may occur as a result of complement activation. Purified human C3a was administered by intracoronary bolus injections into isolated guinea pig hearts. As a function of dose, C3a caused tachycardia, impairment of atrioventricular conduction, left ventricular contractile failure, coronary vasoconstriction, and histamine release. These effects were abolished by cleavage of the COOH-terminal arginine by carboxypeptidase B. The magnitude of C3a-induced tachycardia correlated with the amount of endogenous cardiac histamine released into the coronary effluent. Whereas the tachycardia was markedly reduced by the histamine H2 antagonist cimetidine, the contractile failure and the coronary vasoconstriction caused by C3a were antagonized by the leukotriene antagonist FPL 55712 and by the cyclooxygenase inhibitor indomethacin, respectively. This suggests that histamine, leukotrienes, and vasoactive prostanoates may mediate the various cardiac effects of C3a. Our findings indicate that C3a anaphylatoxin has marked cardiac effects at concentrations that are likely to be attained with a degree of C3 activation commonly seen in various disease states. Thus, our data are compatible with the hypothesis that generation of anaphylatoxins may induce cardiac dysfunction in clinical conditions.
del Balzo
U H
UH
Levi
R
R
Polley
M J
MJ
D000706:Anaphylatoxins / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003176:Complement C3 / Q000031:analogs & derivatives / Q000494:pharmacology*; D015926:Complement C3a; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D000706:Anaphylatoxins; D002867:Chromones; D003176:Complement C3; D010455:Peptides; C044541:complement C3a, des-Arg-(77)-; D002927:Cimetidine; D015926:Complement C3a; C006312:FPL 55712; D007213:Indomethacin