The intestinal injury after hemorrhagic shock and resuscitation exhibits inflammatory elements of reperfusion injury

Abstract

Introduction: Intestinal injury after hemorrhagic shock is well recognized and thought to be a source of significant additional morbidity. A role for inflammatory mediators, particularly the complement system, in the genesis of either the local injury or its systemic consequences has been suspected. We hypothesize that reperfusion damage after hypotension and resuscitation is the cause of the intestinal injury, and that, as a result, the intestine would demonstrate the characteristic immunohistochemistry of reperfusion injury with deposition of IgM and complement. Methods: Male Sprague-Dawley rats were anesthetized and acutely bled to 50% of total blood volume for 90 minutes. The animals were then resuscitated with shed blood and monitored for survival for 72 hours. Small intestine from rats that did not survive the shock period, resuscitation, or 72 hours postoperative period was harvested and fixed in formalin. For comparison, small intestine from two sham rats and all shock animals that survived 72 hours was also harvested and fixed in formalin. Structural microscopic villous injury was assessed with a villous-injury scoring system by hemotoxylin and eosin staining. IgM and C3 deposition were assessed using immunohistochemistry. Results: Intestinal villous damage was demonstrated in all of the rats subjected to hemorrhagic shock and resuscitation as evidenced by hemotoxylin and eosin staining, but not in shams. Rats that died had higher intestinal injury scores than those that survived. Immunohistochemistry showed co-localization of IgM and C3 in those damaged intestinal villi that had not sloughed into the lumen. No microvillous damage, IgM, or C3 was demonstrated in the sham animals. Conclusions: These data demonstrate co-localization of IgM and C3 in the damaged rat intestinal villi of animals that underwent hemorrhagic shock and resuscitation, a characteristic feature of reperfusion injury in both the gut and hindlimb muscle. Treatment of the intestinal reperfusion injury occurring during shock and resuscitation could improve overall survival.