The effects of ABT-229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats.
BACKGROUND
Interdigestive small bowel motility has a regulatory function on the microflora of the upper small bowel. Here we investigate the effects of ABT-229 and octreotide on morphine-induced dysmotility, the accompanying bacterial overgrowth and bacterial translocation.


METHODS
Rats were fitted with jejunal myoelectrodes and a subcutaneous cannula for continuous infusion of saline or morphine. Fasting motility was measured for 6 h on four occasions: one control measurement (day 0) and three measurements on consecutive days (days 1-3) while receiving saline alone (group A), morphine alone (group B), saline + ABT-229 (group C), morphine + ABT-229 (group D), saline + octreotide (group E) or morphine + octreotide (group F). Samples from the mesenteric lymph node complex (MLN), liver, spleen, duodenum and ileum were taken for quantitative microbial culturing on day 4.


RESULTS
Neither ABT-229 nor octreotide increased the number of propagated activity fronts during saline infusion. During morphine-induced dysmotility, ABT-229 induced more propagated activity fronts in group D (13.4, 9.8 and 8.8 per 6 h) than in group B (7.0, 4.5, 3.8 per 6 h) on days 1, 2 and 3 (P < 0.05 for all days) Octreotide did not induce more propagated activity fronts. Disruption of small bowel motility by morphine led to bacterial overgrowth in the duodenum. ABT-229 and octreotide did not reduce the bacterial growth levels. The total incidence of bacterial translocation was significantly higher in the morphine-treated animals than in the saline-treated animals. Neither ABT-229 nor octreotide reduced the bacterial translocation incidence. The number of propagated activity fronts on day 3 and duodenal bacterial growth correlated significantly in groups A, E and F.


CONCLUSIONS
ABT-229, but not octreotide, reduced morphine induced dysmotility. Small bowel bacterial overgrowth and bacterial translocation were not prevented. Fasting small bowel motility has a regulatory function on the intestinal microflora of the upper small bowel.
Nieuwenhuijs
V B
VB
Department of Surgery, University Hospital Utrecht, The Netherlands. GE-onderzoek@chir.azu.nl
van Duijvenbode-Beumer
H
H
Verheem
A
A
Visser
M R
MR
Verhoef
J
J
Gooszen
H G
HG
Akkermans
L M
LM
D000818:Animals; D004347:Drug Interactions; D004386:Duodenum / Q000382:microbiology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007082:Ileum / Q000382:microbiology; D007421:Intestine, Small / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D015282:Octreotide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005765:Gastrointestinal Agents; C114264:Alemcinal; D004917:Erythromycin; D009020:Morphine; D015282:Octreotide