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 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 microm). 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.
Tofukuji
M
M
Department of Surgery, Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Stahl
G L
GL
Metais
C
C
Tomita
M
M
Agah
A
A
Bianchi
C
C
Fink
M P
MP
Sellke
F W
FW
D000818:Animals; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015936:Complement C5a / Q000502:physiology*; D005260:Female; D007082:Ileum / Q000098:blood supply; D007413:Intestinal Mucosa / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D011183:Postoperative Complications / Q000209:etiology / Q000503:physiopathology; D013152:Splanchnic Circulation; D013552:Swine
D015936:Complement C5a