Endogenous endotoxin participates in causing a panenteric inflammatory ileus after colonic surgery

The recovery of postoperative gastrointestinal motor function represents a crucial factor for the outcome of abdominal surgery, the length of hospital stay, and perioperative expenses.1 One of the main reasons for the improved perioperative course after laparoscopic surgery is the significant reduction of postoperative dysmotility compared with open techniques.2–4 However, the mechanism involved in this improvement is largely unknown and major abdominal surgery still requires open procedures. Thus, further investigations are needed to uncover pathophysiologic events underlying postoperative dysmotility and to develop specific therapeutic approaches. Inhibitory sympathetic reflexes and inflammatory events with the coexpression of kinetically active mediators have been emphasized as major factors that are involved in the development of postoperative ileus.5–8 We have previously shown that surgical manipulation of the small intestine or the colon initiates a functionally relevant local inflammatory response within the muscularis layer.7,9 This inflammatory cascade includes the activation of resident muscularis macrophages and subsequently the extravasation of immunocompetent leukocytes.7 Both activated cell populations liberate kinetically active substances, such as nitric oxide (NO) and prostaglandins, which directly mediate postoperative smooth muscle dysfunction.10,11 However, these previously described inflammatory mechanisms are a result of a local, mechanical alteration of the intestine and do not explain generalized panenteric postoperative dysmotility, which involves all segments of the gastrointestinal tract. The total duration of uncomplicated postsurgical ileus mainly depends on the recovery of the colon,6 whereas the complicated longer-lasting paralytic ileus appears to be more a result of an impairment of small bowel activity and smooth muscle dysfunction, respectively.5 In this context, we have previously observed that postoperative colonic ileus, caused by an isolated surgical manipulation of the colon, is associated with a significant delay in intestinal transit.9 However, it is not known if this phenomenon is caused by the manipulated and functionally compromised colon, acting as a downstream barrier, by inhibitory neural reflexes or by inflammatory events within the small intestinal muscularis itself. Furthermore, we have previously demonstrated that a systemic lipopolysaccharide (LPS) challenge likewise results in a functionally relevant inflammatory responses within the small intestinal muscularis.12,13 Thus, we speculated that inflammatory events within the small intestinal muscularis, which occur after colonic manipulation, might, at least partially, be the result of mechanically dislocated bacterial products. Therefore, the objectives of the present study were as follows: 1) to investigate small intestinal motility after colonic surgery independently of colonic motor function, 2) to determine the impact of spinal reflexes versus the role of altered intrinsic contractile systems in the development of postoperative small intestinal dysmotility, 3) to determine if colonic manipulation initiates a distinct and functionally relevant inflammatory response within the small intestinal muscularis, and 4) to define the role of the gut flora in the initialization of this mechanism.