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We investigated the effects of jejunoileal denervation with or without ischemia–reperfusion on mucosal characteristics and small intestinal structure. Growing pigs underwent sham laparotomy, jejunal transection, or extrinsic jejunoileal denervation with or without in situ ischemia–reperfusion. Small intestinal morphology, crypt cell proliferation, enterocyte ultrastructure, and disaccharidase activities were analyzed from jejunum and ileum after eight weeks. Immunohistological analysis of the ileum showed no staining of catecholaminergic neurons after extrinsic denervation. Neural isolation of the jejunoileum with or without ischemia–reperfusion injury reduced weight gain and villous enterocyte density in the ileum, abolished the proximodistal gradient of sucrase activity, and increased mucosal thickness, villus height, and villus surface area in the ileum. However, gross jejunoileal morphology, crypt cell proliferation, and enterocyte ultrastructure remained unchanged. In conclusion, jejunoileal denervation in growing pigs selectively modulates constitutional mucosal characteristics in the ileum, presumably due to altered enterocyte turnover, without a decrease in small intestinal absorptive surface area. These changes are independent of short ischemia and subsequent reperfusion.

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.

Background/Purpose Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum. Methods Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. Results After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups. Conclusions These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum.

Background/Purpose: Small bowel transplantation impairs enteric function, necessitating transection, extrinsic denervation, and ischemia-reperfusion of the small intestine. The authors investigated how each of these nonimmunologic insides of the transplantation procedure modulates biodynamics of cholesterol and absorption of lipids. Methods: Twenty-three pigs with similar food, cholesterol, and fat intake underwent sham laparotomy (group 1), transection (group 2), extrinsic jejunoileal denervation (group 3), or a model of autotransplantation, including extrinsic jejunoileal denervation with in situ ischemia-reperfusion (group 4). Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis, and absorption, were measured after 2 and 8 weeks. Results: When compared with sham laparotomy and transection groups, denervation and autotransplantation significantly decreased weight gain and increased plasma cholesterol precursors and fecal excretion of bile acids. In relation to sham operated animals, transection alone modestly increased plasma plant sterols at 2 weeks and biliary secretion and mass absorption of cholesterol. The latter changes were not observed after denervation or autotransplantation, ie, fractional and total absorption of cholesterol were significantly decreased in autotransplanted pigs when compared with transected controls. As compared with all the other groups, autotransplantion significantly increased bacterial metabolites of neutral sterols in feces and net fecal elimination of cholesterol, mainly as bile acids. Conclusions: Extrinsic autonomic denervation of the jejunoileum, with or without synchronous ischemia-reperfusion, results in increased cholesterol synthesis, bile acid malabsorption, and decreased weight gain. Cholesterol malabsorption may develop gradually after intestinal autotransplantation, and even a short period of ischemia further impairs absorptive function of the denervated jejunoileum, resulting in increased fecal elimination of cholesterol mainly as bile acids.