Endotoxin-induced enteric hypomotility in jaundiced loops in vitro

ABSTRACT

Biliary obstruction may be accompanied by systemic endotoxemia due to increased growth of enteric microbiota and failure of hepatic clearance mechanisms. This endotoxemia is related to increased postoperative morbidity and mortality. An increased growth of the aerobic flora has been demonstrated experimentally in the presence of biliary obstruction, and in previous studies we observed intestinal hypomotility of jaundiced loops in vitro. To determine the ileal motor response in the presence of jaundice caused by biliary obstruction and in the presence of endotoxemia, an in vitro study was carried out on ileal segments from 10 female Holtzman rats, 2-3 months old, weighing 200 to 300 g, divided into two groups (N = 5) A, washed loops of jaundiced rats, and B, washed loops of jaundiced rats to which endotoxin was added. On the seventh postoperative day, we evaluated the effect of exogenous endotoxin (E. coli 0111B4, Sigma) on the motor response to acetylcholine of distal ileal segments isolated from both animal groups. A 4-cm ileal segment, located 10 cm from the ileal papilla, was removed and studied in an organ chamber in order to assess dose-response curves to acetylcholine. There was an increase in threshold dose in jaundiced loops with intraluminally injected endotoxin when compared with the loops without intraluminal endotoxin (291 + 188 vs 8.5 + 6.7 muM, P<0.05). The maximum contraction was reduced in jaundiced loops with intraluminal endotoxin in relation to control loops (5.3 + 1.7 vs 18.7 + 4.8 mm, P<0.05), and pD2 was also reduced in jaundiced loops with intraluminal endotoxin in relation to control loops (2.4 + 0.6 vs 3.7 + 0.5, P<0.05). There was no statistical difference between jaundiced loops with and without intraluminal endotoxin when the maximal contraction doses were compared (86 + 66 vs 48 + 22 mM, P>0.05). These results demonstrate that intraluminal endotoxin depressed enteric motility in jaundiced rats.