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Ann Thorac Surg 2000;69:799-807
© 2000 The Society of Thoracic Surgeons

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Original Articles

Mesenteric dysfunction after cardiopulmonary bypass: role of complement C5a

^a Department of Surgery, Beth Israel-Deaconess Medical Center, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
^b Center For Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

Address reprint requests to Dr Sellke, Division of Cardiothoracic Surgery, Beth Israel-Deaconess Medical Center, 110 Francis St, LMOB 2A, Boston, MA 02215
e-mail: fsellke{at}caregroup.harvard.edu

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 off CPB for an additional 2 hours. Antiporcine C5a monoclonal antibody (C5a MAb) was administered 20 minutes before onset of CPB to 6 pigs; 6 controls received saline vehicle. Total complement activity, ileal myeloperoxidase, and indices of ileal integrity were examined.

Results. Treatment with C5a MAb ameliorated CPB-induced abnormalities in endothelium-dependent relaxation to ADP and substance P, and the hypercontractile response to phenylephrine of ileal microvessels (88 to 168 µm). Ileal myeloperoxidase activity [units/g protein] was 41 ± 11 in the C5a MAb group, 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 flow and mucosal pH, edema formation, and epithelial permeability deteriorated 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 flow regulation. Inhibition of C5a limits neutrophil-mediated impairment of ileal microvascular regulation after bypass, but does not improve extravascular mesenteric dysfunction after CPB.

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