ALTERATIONS IN RAT INTESTINAL TRANSIT BY MORPHINE PROMOTE BACTERIAL TRANSLOCATION

Translocation of enteric microorganisms from the intestinal tract to e xtraintestinal sites has been proposed as an early step in the develop ment of gram-negative sepsis. This study examined the role of altered bowel transit in influencing intestinal bacteriostasis and bacterial t ranslocation using morphine as a pharmacologic inhibitor of such trans it. In the first experiment, either normal saline (N = 8) or morphine sulfate (20 mg/kg; N = 8) was injected subcutaneously. Two hours later , morphine (7.5 mg/kg) was infused subcutaneously for an additional 22 hr; control animals received saline alone. After completion of this r egimen, a volume of 0.2 ml of 2.5 mM FITC dextrans (10,000 daltons) we re injected intraduodenally in each group. The bowel was removed 25 mi n later, divided into 5-cm segments, and the content of dextrans measu red. Small bowel propulsion was expressed as the geometric center of t he distribution of dextrans throughout the intestine (in percentage le ngth of small bowel). Gut propulsion was significantly reduced after m orphine treatment as compared to controls (32.8 +/- 8.2% vs 55.8 +/- 4 .0%; P < 0.01). In 16 additional rats, saline or morphine was again ad ministered as described. After 24 hr, samples were obtained from the m esenteric lymph node (MLN) complex, blood, spleen, liver, duodenum, je junum, ileum, and cecum for standard bacteriology. The bacterial count s increased significantly in each intestinal segment following morphin e treatment. Microorganisms translocated to the MLN complex in 5, and to distant sites in four of eight morphine-treated animals, respective ly. Translocation to the MLN complex occurred in only one of eight con trols (P < 0.05); no translocation to distant sites occurred in contro l animals. We conclude that the morphine-induced prolongation in bowel transit promotes bacterial translocation secondary to an overgrowth o f enteric bacteria in the intestinal lumen.