HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Syed Raza Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shastri, K. A. Articles by Raza, S. Search for Related Content PubMed PubMed Citation Articles by Shastri, K. A. Articles by Raza, S.

J Thorac Cardiovasc Surg 1997;114:482-488
© 1997 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

COMPLEMENT ACTIVATION BY HEPARIN-PROTAMINE COMPLEXES DURING CARDIOPULMONARY BYPASS: EFFECT OF C4A NULL ALLELE

This work was supported by grant R29-HL47858, funded by the National Heart, Lung, and Blood Institute and the Office of Research of Women's Health, the National Institutes of Health, and also in part by the Richard E. Wahle Research Fund of the State University of New York at Buffalo, N.Y.

Received for publication Sept. 20, 1996; revisions requested Nov. 11, 1996; revision received May 2, 1997; accepted for publication May 2, 1997. Address for reprints: Kaushik A. Shastri, MD, 11 1-H, Veterans Administration Medical Center, 3495 Bailey Ave., Buffalo, NY 14215.

Abstract

Objectives: The first objective was to determine the effect of inherited differences in the classic pathway complement protein C4 on complement activation by heparin-protamine complexes in cardiac surgery. Specifically, we hypothesized that patients with heterozygous C4A null phenotype (A0BB), who have decreased amounts of C4A, may have increased complement activation because of reduced clearance of heparin-protamine complexes. The second objective was to determine whether heparin-protamine-induced complement activation correlated with postoperative pulmonary shunt fractions. Methods: C4 typing was performed by agarose gel immunofixation and crossed immunoelectrophoresis. Complement activation was measured by radioimmunoassay of C3a and C4a before cardiopulmonary bypass, after bypass, and after protamine infusion. Shunt fractions were calculated from blood gases. Results: Of the 79 patients, 18 expressed heterozygous C4A null allele (A0BB), 16 had heterozygous C4B null allele (AAB0), three had homozygous C4B null alleles (AA00), and the rest expressed both C4A and C4B alleles (AABB). Patients with heterozygous C4A null allele had significantly increased plasma levels of C4a after protamine neutralization of heparin (C4a of 2862 ±375 ng/ml; mean ± standard error of the mean) when compared with patients with normal expression of C4 alleles (AABB) (C4a of 1580 ± 141 ng/ml) or heterozygous C4B null allele (C4a 1526 ± 208 ng/ml). Pulmonary shunt fractions obtained after the operation correlated with the classic pathway complement activation by heparin-protamine complexes, but not with alternative pathway complement activation during cardiopulmonary bypass. Conclusions: Patients with heterozygous C4A null phenotype have increased complement activation by heparin-protamine complexes during cardiac operations, possibly because of their defective clearance. The classic pathway complement activation by heparin-protamine interaction correlates with postoperative pulmonary shunt fractions.

This article has been cited by other articles:

				S. A. Pecsi, G. H. Almassi, R. B. Bojrab, and P. S. Pagel Management of Hereditary Angioedema During Off-Pump Coronary Arterial Surgery Ann. Thorac. Surg., March 1, 2008; 85(3): 1079 - 1081. [Abstract] [Full Text] [PDF]

				K. S. Kilgore, E. J. Tanhehco, K. B. Naylor, and B. R. Lucchesi Ex Vivo Reversal of Heparin-Mediated Cardioprotection by Heparinase After Ischemia and Reperfusion J. Pharmacol. Exp. Ther., September 1, 1999; 290(3): 1041 - 1047. [Abstract] [Full Text]