NEUTROPHIL DEPLETION ATTENUATES HUMAN INTESTINAL REPERFUSION INJURY

Intestinal ischemia/reperfusion injury (I/R) results from reactive oxy gen metabolites generated by the xanthine oxidase system and activated neutrophils (PMN). In animal models, removing PMN from initial reperf usate has consistently decreased tissue injury. This experiment was de signed to test this potential clinical treatment in human bowel subjec ted to I/R. The extent of reperfusion injury was assessed by measuring the activity of mucosal alkaline phosphatase (A phi), which is a spec ific marker of reperfusion injury. Human small intestine (n = 13) obta ined at the time of organ harvest for transplantation was perfused for 60 min on an ex vivo perfusion circuit. Reperfusate consisted of auto logous blood passed through a leukocyte filter (n = 6) or unfiltered b lood (n = 7). Control intestine was sampled at harvest, after transpor t to the lab on ice (cold ischemia), and after 60 min warm ischemia. M ucosa was homogenized and assayed for A phi activity by cleavage of p- nitrophenyl phosphate. A phi activity (nmole/mg/min) was not decreased after either cold (774 +/- 37) or warm (753 +/- 40) ischemia compared to freshly harvested bowel (770 +/- 51). Both reperfused segments sho wed a significant decrease in A phi activity compared to controls (P < 0.05); however, reperfusion with leukocyte-filtered blood attenuated the decrease in enzyme activity compared to unfiltered blood (327 +/- 30 vs 506 +/- 25, P < 0.05), constituting an apparent reduction in inj ury of 35%. The observation that the severity of reperfusion injury wa s decreased by removal of PMN from the reperfusate demonstrates the ef ficacy of this strategy in human intestine for the first time. (C) 199 4 Academic Press, Inc.