Complement inhibition prevents gut ischemia and endothelial cell dysfunction after hemorrhage/resuscitation.
BACKGROUND
Complement, a nonspecific immune response, is activated during hemorrhage/resuscitation (HEM/RES) and is involved in cellular damage. We hypothesized that activated complement injures endothelial cells (ETCs) and is responsible for intestinal microvascular hypoperfusion after HEM/RES.


METHODS
Four groups of rats were studied by in vivo videomicroscopy of the intestine: SHAM, HEM/RES, HEM/RES + sCR1 (complement inhibitor, 15 mg/kg intravenously given before resuscitation), and SHAM + sCR1. Hemorrhage was to 50% of mean arterial pressure for 60 minutes followed by resuscitation with shed blood plus an equal volume of saline. ETC function was assessed by response to acetylcholine.


RESULTS
Resuscitation restored central hemodynamics to baseline after hemorrhage. After resuscitation, inflow A1 and premucosal A3 arterioles progressively constricted (-24% and -29% change from baseline, respectively), mucosal blood flow was reduced, and ETC function was impaired. Complement inhibition prevented postresuscitation vasoconstriction and gut ischemia. This protective effect appeared to involve preservation of ETC function in the A3 vessels (SHAM 76% of maximal dilation, HEM/RES 61%, HEM/RES + sCR1 74%, P < .05).


CONCLUSIONS
Complement inhibition preserved ETC function after HEM/RES and maintained gut perfusion. Inhibition of complement activation before resuscitation may be a useful adjunct in patients experiencing major hemorrhage and might prevent the sequelae of gut ischemia.
Fruchterman
T M
TM
Department of Surgery, University of Louisville, KY 40292, USA.
Spain
D A
DA
Wilson
M A
MA
Harris
P D
PD
Garrison
R N
RN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003167:Complement Activation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000032:analysis*; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D011951:Receptors, Complement; D014665:Vasodilator Agents; C082885:soluble complement inhibitor 1; D009599:Nitroprusside; D000109:Acetylcholine