Abstracts
1998 Digestive Disease Week

#979

N-ACETYLCYSTEINE ABROGATES THE SYSTEMIC RESPONSE TO MURINE INTESTINAL ISCHEMIA/REPERFUSION. D.A. Rigberg, T.A. Blinman, J.S. Lane, F.S. Kim, O.J. Hines, D.W. McFadden, C.F. Chandler, Division of General Surgery, UCLA, Los Angeles, California.

Intestinal ischemia/reperfusion (IR) produces a severe systemic inflammatory response marked by high levels of serum cytokines as well as distant organ injury, particularly neutrophil-mediated lung injury. Cytokine expression and neutrophil activation in ischemia have been linked to oxygen radical formation that accompanies reperfusion. We hypothesized that the antioxidant agent N-acetylcysteine (NAC) would decrease both the systemic inflammatory cytokine response and pulmonary neutrophil sequestration in a murine model of intestinal IR.

Methods: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent laparotomy alone (S). Group 2 underwent 45 minutes of cephalic mesentery artery occlusion followed by 3-hour reperfusion (I). Group 3 underwent sham operation plus NAC treatment (50 mg/kg ip, 1 hour preop) (S/N). Group 4 received IR with NAC (I/N). Animals were sacrificed 3 hours after reperfusion. Serum cytokines were determined by ELISA (pg/ml). Lung tissue was harvested for myeloperoxidase activity (U/gm). Histological scoring of fixed jejunal sections was performed by two blinded investigators.

Results:

Mean  ± SEM; *=P<0.05 vs. IR. No histological differences were seen between
treated and non-treated ischemic bowel.

Conclusions: NAC administration decreased serum levels of the proinflammatory cytokine IL-6 and the counter-inflammatory cytokine IL-10 in this model of murine gut IR. In addition, NAC abolished accumulation of activated neutrophils in the lungs of IR-treated animals. NAC may find a role in the treatment of the systemic consequences of IR injury.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.