Mesenteric dysfunction after cardiopulmonary bypass: Role of complement C5a

Background. We investigated the effects of cardiopulmonary bypass (CPB) on ileal homeostasis, and the influence of functional inhibition of complement C5a on CPB-induced mesenteric injury. Methods. Pigs were perfused on CPB for 1 hour and then perfused oh CPB for an additional 2 hours. Anti porcine C5a monoclonal antibody (C5a MAb) was a dministered 20 minutes before onset of CFB to 6 pigs; 6 controls received s aline vehicle. Total complement activity, ileal myeloperoxidase, and indice s of ileal integrity were examined. Results. Treatment with C5a MAb ameliorated CPB-induced abnormalities in en dothelium-dependent relaxation to ADP and substance P, and the hypercontrac tile response to phenylephrine of ileal microvessels (88 to 168 mu m) Ileal myeloperoxidase activity [units/g protein] was 41 +/- 11 in the C5a MAb gr oup, compared to 83 +/- 13 in the saline group (19 +/- 10 base line). Total hemolytic complement activity was similar in the C5a MAb and saline groups (0.6 +/- 0.2 and 0.7 +/- 0.2 CH50 units). During CPB, ileal mucosal blood now and mucosal pH, edema formation, and epithelial permeability deteriorat ed similarly in saline and C5a MAb groups. Inducible nitric oxide synthase (iNOS) mRNA expression was similar before and after CPB. Conclusions. CPB is associated with significant physiologic alterations in mucosal perfusion, epithelial permeability, edema formation, and blood now regulation. Inhibition of C5a limits neutrophil-mediated impairment of ilea l microvascular regulation after bypass, but does not improve extravascular mesenteric dysfunction after CPB. (C) 2000 by The Society of Thoracic Surgeons.