Circulation Research, Vol 65, 847-857, Copyright © 1989 by American Heart Association

ARTICLES

Cardiac anaphylaxis. Complement activation as an amplification system

U del Balzo, MJ Polley and R Levi
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.

Complement is activated, and C3a and C5a anaphylatoxins are generated during hypersensitivity reactions clinically associated with cardiopulmonary collapse. The administration of C3a or C5a to nonsensitized isolated guinea pig hearts mimics the events caused by antigen challenge of sensitized hearts (i.e., cardiac anaphylaxis) in the absence of complement. Thus, complement-derived anaphylatoxins may participate in immediate hypersensitivity reactions in which the heart is a target organ. To assess the contribution of complement activation and anaphylatoxin generation to cardiac dysfunction, we have elicited anaphylaxis in isolated guinea pig hearts in the presence of complement and found that the ensuing dysfunction is markedly enhanced. This amplification is most likely attributable to anaphylatoxin formation because 1) inactivation of C3 or selective C3 depletion, i.e., the loss of the component responsible for the formation of the anaphylatoxins C3a and C5a, prevents complement-induced exacerbation of cardiac anaphylaxis, whereas reconstitution with C3 and C5, or even only C3, restores it; in fact, the greater the C3 content at the time of antigen challenge, the more intense the anaphylactic crisis; and 2) the severity of cardiac anaphylaxis is markedly reduced by preexposure to C3a, and this reduction is directly related to the dose of C3a injected and to the amount of endogenous cardiac histamine depleted by C3a before antigen challenge. Complement-derived anaphylatoxins appear to promote the same mediator release that has been initiated by the antigen-antibody reaction; thus, complement activation functions as an amplification system in cardiac anaphylaxis.

This article has been cited by other articles:

				J. Szebeni, L. Baranyi, S. Savay, M. Bodo, J. Milosevits, C. R. Alving, and R. Bunger Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1050 - H1058. [Abstract] [Full Text] [PDF]

				M. D.M. Engelmann and J. H. Svendsen Inflammation in the genesis and perpetuation of atrial fibrillation Eur. Heart J., October 2, 2005; 26(20): 2083 - 2092. [Abstract] [Full Text] [PDF]

				J. Dernellis and M. Panaretou Relationship between C-reactive protein concentrations during glucocorticoid therapy and recurrent atrial fibrillation Eur. Heart J., July 1, 2004; 25(13): 1100 - 1107. [Abstract] [Full Text] [PDF]

				P. Bruins, H. t. Velthuis, A. P. Yazdanbakhsh, P. G. M. Jansen, F. W. J. van Hardevelt, E. M. F. H. de Beaumont, C. R. H. Wildevuur, L. Eijsman, A. Trouwborst, and C. E. Hack Activation of the Complement System During and After Cardiopulmonary Bypass Surgery : Postsurgery Activation Involves C-Reactive Protein and Is Associated With Postoperative Arrhythmia Circulation, November 18, 1997; 96(10): 3542 - 3548. [Abstract] [Full Text]

				L. E. Rubin and R. Levi Protective Role of Bradykinin in Cardiac Anaphylaxis : Coronary-Vasodilating and Antiarrhythmic Activities Mediated by Autocrine/Paracrine Mechanisms Circ. Res., March 1, 1995; 76(3): 434 - 440. [Abstract] [Full Text]