Complement does not mediate the cardiac inflammatory response initiated by myocardial ischemia-reperfusion during cardiopulmonary bypass

Abstract

Introduction: This study was designed to test the hypothesis that complement mediates the cardiac inflammatory response resulting from ischemia during cardiopulmonary bypass (CPB). Methods: Paired aortic and coronary sinus blood samples were collected from patients undergoing elective, first-time coronary bypass grafting with CPB (n = 17). Sera was analyzed using ELISA to detect levels of C3a and C5a. Histamine, as a marker of C3a or C5a stimulation of the inflammatory response, was also measured. Atrial tissue samples were collected before and after CPB. Tissue was immunohistochemically stained for alternative and classical complement pathway proteins C1q and factor Bb. Results: Systemic C3a levels increased during CPB (837 ± 599 ng/ml). Histamine, C3a and C5a levels across the heart (coronary sinus minus aortic values) were not significantly different at any time-point (baseline: 0.27 ± 1.45, 29 ± 82, -0.45 ± 2.5; reperfusion: -0.35 ± 0.42, -55 ± 211, 0.25 ± 1.20 for histamine, C3a and C5a respectively). Immunohistochemical stains showed no deposition of C1q or Factor Bb. Conclusions: The myocardium is not a source of the complement activation seen during the ischemia-reperfusion of CPB. The elevated levels of C3a created during CPB does not stimulate cardiac inflammation. Complement does not play a significant role in post-CPB cardiac inflammatory state.