Acute pancreatitis severity is exacerbated by intestinal ischemia-reperfusion conditioned mesenteric lymph

Abstract

Objective. To determine the effect of intestinal ischemia-reperfusion (IIR) on acute pancreatitis (AP) and the role of mesenteric lymph. Summary background data. Intestinal ischemia is an early feature of AP and is related to the severity of disease. It is not known whether this contributes to the severity of AP or is a consequence. Methods. Two experiments are reported here using intravital microscopy and a rodent model of mild acute pancreatitis (intraductal 2.5% sodium taurocholate). In the first, rats had an episode of IIR during AP that was produced by temporary occlusion of the superior mesenteric artery (30min or 3 3 10min) followed by 2h reperfusion. In a second study rats with AP had an intravenous infusion of mesenteric lymph collected from donor rats that had been subjected to IIR. In both experiments the pancreatic erythrocyte velocity (EV), functional capillary density (FCD), leukocyte adherence (LA), histology and edema index were measured. Results. The addition of IIR to AP caused a decline in the pancreatic microcirculation greater than that of AP alone (EV 42% of baseline vs. 73% of baseline AP alone, FCD 43% vs 72%, LA 7 fold increase vs 4 fold increase). This caused an increased severity of AP as evidenced by 1.4--1.8 fold increase of pancreatic edema index and histologic injury respectively. A very similar exacerbation of microvascular failure and increased pancreatitis severity was then demonstrated by the intravenous infusion of IIR conditioned mesenteric lymph from donor animals. Conclusions. Unidentified factors released into the mesenteric lymph following IIR injury are capable of exacerbating AP. This highlights an important role for the intestine in the pathophysiology of AP pathogenesis and identifies mesenteric lymph as a potential therapeutic target.