Octreotide in the treatment of small intestinal dysfunction after a model of jejunoileal autotransplantation in the pig.
Enteric denervation and ischemic injury contribute to dysmotility and malabsorption following intestinal transplantation. We hypothesized that, by prolonging bowel transit and by ameliorating dysmotility, octreotide (OT) may improve cholesterol and bile acid absorption after jejunoileal autotransplantation. Seventeen pigs with fixed food intake underwent either jejunal transection (n = 6), or jejunoileal autotransplantation, which includes extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia (n = 11). Five randomly chosen autotransplanted animals received intramuscular long-acting OT (10 mg) once a month. After 8 weeks, weight gain, intestinal transit time, fecal excretion of bile acids and cholesterol, and fractional cholesterol absorption were determined. Jejunal and ileal specimens were collected for histochemical analyses. Plasma cholestenol and campesterol, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. Following jejunoileal autotransplantation, octreotide treatment significantly increased the median intestinal transit time from 22.8 to 24.8 h and the median body weight gain from 166 to 187%. Jejunoileal autotransplantation significantly increased fecal bile acid excretion, plasma cholestenol, and bacterially modified fecal neutral sterols, and decreased absorption of cholesterol, plasma campesterol, and biliary cholesterol secretion. These changes were not significantly modified by OT treatment. Bowel wall and mucosal structure, mucosal proliferation, and weight or microvilli showed no statistically significant differences between autotransplanted animals with or without OT treatment. Findings of the present study suggest that octreotide prolongs intestinal transit time and improves weight gain after jejunoileal autotransplantation, but has no effect on malabsorption of cholesterol and bile acids.
Section of Pediatric Surgery, Children's Hospital, University of Helsinki, Stenbäckinkatu 11, P.O. Box 281, 00029 Helsinki, Finland. mikko.pakarinen@tiscali.co.uk
Mikko P
MP
Pakarinen
Jouni
J
Lauronen
Paula
P
Pirinen
Pekka
P
Kuusanmäki
Peter
P
Raivio
Jorma
J
Halttunen
D000818:Animals; D017763:Autonomic Denervation; D001647:Bile Acids and Salts / Q000493:pharmacokinetics; D049109:Cell Proliferation; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007082:Ileum / Q000473:pathology / Q000637:transplantation*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000473:pathology; D007511:Ischemia; D007583:Jejunum / Q000473:pathology / Q000637:transplantation*; D008198:Lymph Nodes / Q000601:surgery; D017538:Mesenteric Artery, Superior / Q000601:surgery; D015282:Octreotide / Q000627:therapeutic use*; D011897:Random Allocation; D013552:Swine; D013997:Time Factors; D014182:Transplantation, Autologous; D015430:Weight Gain
D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D002784:Cholesterol; D015282:Octreotide