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Complement Activation during Cardiopulmonary Bypass — Evidence for Generation of C3a and C5a Anaphylatoxins

List of authors.
  • Dennis E. Chenoweth, Ph.D., M.D.,
  • Steven W. Cooper, B.A.,
  • Tony E. Hugli, Ph.D.,
  • Robert W. Stewart, M.D.,
  • Eugene H. Blackstone, M.D.,
  • and John W. Kirklin, M.D.

Abstract

We observed complement activation in 15 adults undergoing total cardiopulmonary bypass. Plasma levels of C3a were significantly elevated (P<0.0001) at the beginning of the procedure, and they continued to increase steadily thereafter. At the end of the procedure, C3a levels were more than five times higher than preoperative levels. Plasma levels of C5a (a factor that binds avidly to neutrophils) did not change significantly during cardiopulmonary bypass. Instead, there was significant neutrophilia (P = 0.03) during bypass, and significant transpulmonary neutropenia (P = 0.0002) occurred when cardiopulmonary circulation was reestablished at partial bypass. The neutropenia is consistent with pulmonary-vascular sequestration of C5a-activated granulocytes. We also found that incubation of blood with the nylon-mesh liner of bubble oxygenators, as well as vigorous oxygenation of whole blood, promotes conversion of complement. We conclude that the complement-derived inflammatory mediators C3a and C5a produced during extracorporeal circulation may contribute to the pathogenesis of "post-pump syndromes." (N Engl J Med. 1981; 304: 497–503.)

Funding and Disclosures

Supported by grants (HL 11310, HL 96411, and HL 25658) from the National Institutes of Health and by the Eli Lilly Company.

Portions of this work were done while Dr. Chenoweth was an Established Investigator of the American Heart Association.

This article is publication no. 2269 from the Research Institute of Scripps Clinic.

We are indebted to Dr. Robert B. Karp and Nicholas T. Kouchoukos for their cooperation during this study and to Miss Holly Wimer for her assistance in the preparation of the manuscript.

Author Affiliations

From the Department of Molecular Immunology, Scripps Clinic and Research Foundation, and the Department of Surgery, University of Alabama, Birmingham, Ala. Address reprint requests to Dr. Chenoweth at the Department of Molecular Immunology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.

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