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This study investigates the effects of ilealautotransplantation on morphology, crypt cellproliferation, and brush border disaccharidases of theremaining jejunoileum and colon in growing pigs with 75% proximal small bowel resection. Resection wasperformed on 30 pigs, of which 15 underwent anautotransplantation of the remaining ileum. Theautotransplanted pigs showed reduced weight gain andremnant ileal length when compared to the resectedcontrols. In the autotransplanted pigs, small boweldiameter and weight, mucosal weight and protein content,villus height and surface area, crypt depth, and the number of proliferating crypt cells werereduced similarly both in the intact jejunum and in theautotransplanted ileal remnant. Autotransplantation alsodecreased the number of proliferative crypt cells of the colon. Specific activities of maltaseand sucrase tended to increase in the autotransplantedileal remnant, whereas the total enzyme activitiesdecreased. These results suggest that ilealautotransplantation disturbs postresectional adaptation of theremaining gut.

Contribution of different gut segments to plant sterol absorption, adaptation of plant sterol absorption after partial small bowel resection, and effects of gut transplantation (necessitates extrinsic autonomic denervation and lymphatic disruption) on plant sterol biodynamics are unclear. We studied the consequences of massive proximal small bowel resection and autotransplantation of the remaining ileum on the adaptive absorption and biodynamics of plant sterols. Dietary, fecal, biliary, hepatic and plasma plant sterols, fecal elimination and absorption of cholesterol, small bowel morphology, and intestinal transit were determined before (n = 5) and at 4, 8, and 14 wk after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum (n = 15) or transection (n = 5). Proximal gut resection significantly reduced cholesterol absorption efficiency; percentage absorption and biliary secretion of plant sterols; plasma, biliary and hepatic campesterol-to-cholesterol proportions; and sitosterol proportions in plasma and bile. Autotransplantation of the remaining ileum further significantly decreased cholesterol absorption efficiency; percentage absorption and biliary secretion of campesterol; campesterol proportions in plasma, bile and liver; and plasma proportions of sitosterol while increasing fecal excretion of neutral and acidic steroids. Plasma proportions of the two plant sterols, but absorption of just campesterol, were gradually improved with increasing cholesterol absorption and villus height after proximal gut resection; the same result was observed to a lesser degree after ileal autotransplantation. In addition, significant positive correlations were found between percentage cholesterol and campesterol absorption and the plasma plant sterol proportions in both proximal resection groups, between campesterol absorption and ileal villus height in the resection group, and between campesterol absorption and intestinal transit time in the autotransplantation group. In conclusion, plasma campesterol and sitosterol closely reflect absorption of cholesterol and plant sterols from intact and autotransplanted ileum during adaptation to proximal gut resection. A loss of proximal gut absorptive surface impairs cholesterol and campesterol absorption more than sitosterol absorption, the latter being apparently less dependent on available jejunal villus surface area.

The value of mucosal biopsies in evaluating small bowel rejection is controversial. In this study, the value of mucosal biopsies was estimated in unmodified porcine small bowel rejection. Ten animals received the distal half of the small bowel as a heterotopic loop (Thiry-Vella loop). The allografts were followed by proximally and distally harvested full-thickness and mucosal biopsies every other day, starting from the 3rd day and continuing until the grafts became necrotic. The histological parameters in both types of biopsies were semiquantitatively scored from 0 to 3 and compared with each other. The difference in mean values on the subsequent days was not remarkable, the results favoring slightly higher values in full-thickness than in mucosal biopsies. Our results suggest that multiple mucosal biopsies are adequate in monitoring morphological changes of small bowel grafts during rejection and that the proximal and distal ileum are similarly affected by acute rejection.

Cholesterol, long-chain fatty acids, and fat-soluble vitamins are absorbed mainly in the upper small intestine and bile acids in the terminal ileum. This study determined the consequences of ileal autotransplantation on cholesterol metabolism, plasma fatty acids, and vitamin A absorption.Plasma lipids, cholesterol precursors, plant sterols, cholestanol, fatty acids, vitamin A absorption, and animal growth were studied for 3 months after transection (n = 5), jejunal (50%) resection (n = 7), jejunal (50%) resection combined with orthotopic ileal autotransplantation (n = 7), and enterectomy (n = 7).Cholesterol precursor to cholesterol proportions in plasma (reflect cholesterol synthesis) remained unchanged after transection and jejunal resection. The plasma plant sterol proportions (reflect cholesterol absorption) and retinol absorption increased after transection and less significantly after jejunal resection, whereas plasma fatty acid compositions were virtually unchanged. Transplantation of ileum and enterectomy amended up to sixfold the precursor proportions (p0.05 versus transection or jejunal resection) and impaired body weight gain. The plant sterol proportions, vitamin A absorption, and plasma cholesterol levels, respectively, were significantly (p0.05) decreased after transplantation when compared with those of the transected control group but remained markedly higher than those in the enterectomized group. Linoleic acid was significantly (p0.05 versus transection) decreased, whereas monoenoic fatty acids and eicosatrienoic acid were increased (p0.05 versus jejunal resection) in plasma lipids.These results indicate that autotransplantation of ileum in pigs that have undergone jejunectomy impairs sterol, essential fatty acid, and vitamin A absorption so that plasma cholesterol levels decrease despite markedly increased cholesterol synthesis and that these changes clearly exceed those found after jejunal resection alone.

Using nonimmunosuppressed piglet small bowel grafts, we performed a detailed histological study on acute rejection and analyzed altogether 45 different histological parameters throughout the bowel wall, in 10 allografts and 6 autografts. Heterotopic grafts were followed by full-thickness biopsies every other day beginning on the 3rd day after transplantation. The parameters were scored from 0 to 3 according to the severity of the change and the values of every variable were compared statistically between the 2 groups. The earliest significant changes, beginning on days 3-5, were infiltration of inflammatory cells and pyroninophilia among these cells in lamina propria; edema, fibrosis, and inflammation in submucosa and muscularis; vacuolar degeneration of myocytes; and endothelial and intimal changes in vessels. Villous blunting and cuboidal epithelium were the other early markers. On day 7, the epithelial and vascular changes became most significant. We want to emphasize especially the vascular parameters: endothelial swelling and proliferation, intimal thickening, intramural inflammation, and obliteration of the lumen. The dilatation of lymph vessels and changes of Peyer's patches had no value in the estimation of rejection. All allografts became necrotic by day 11 after transplantation.

Massive small bowel resection increases ileal villus height as part of normal adaptation. However, despite no gut loss, autotransplantation of the entire small intestine also increases ileal villus height. Our aim was to test whether similar modulation of enterocyte proliferation and apoptosis underpin these comparable increases in villus height. Fifteen pigs were randomly assigned for laparotomy (n=5), 75% proximal small bowel resection (n=5), or jejunoileal autotransplantation (n=5). Eight weeks postoperatively, full-thickness small bowel sections underwent routine immunohistochemistry for cell cycle inhibitors (p53, p21, and p27), antiapoptotic Bcl-2, and proapoptotic bax. The specimens were analyzed semiquantitatively, and the number of intensively positive epithelial cells for each group was compared from 20 digital images (0.32 mm(2)/image). Compared with laparotomy, small bowel resection decreased the number of p27-positive enterocytes in both jejunum and ileum, increased the number of bax-expressing cells in ileum, but decreased the number of bax-expressing cells in jejunum. In contrast, compared with laparotomy, jejunoileal autotransplantation altered neither mucosal bax nor p27 expression. In all groups, Bcl-2 expression was similarly confined to inflammatory cells of the lamina propria, while both p53 and p21 were negative. We conclude that long-term alterations in the enterocytic expression of certain cell cycle and apoptosis markers (p27 and bax) accompany small bowel resection. These changes differ between the jejunum and the ileum and are not seen after whole small bowel autotransplantation. Therefore, increased ileal villus height after autotransplantation, despite resembling postresectional intestinal adaptation, is underpinned by different regulation of enterocyte proliferation and apoptosis.

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, 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.

We investigated the effects of ileum allotransplantation and chronic graft rejection on the synthesis and absorption of cholesterol. Twenty pigs underwent intestinal transection or ileum transplantation, in which the distal half of the jejunoileum was replaced with an ileal autograft or allograft. Conventional triple therapy with cyclosporine (10 mg/kg per day), azathioprine and methylprednisolone was tapered to cyclosporine (5 mg/kg per day) after 10 weeks. Serum lathosterol and campesterol, respective markers of cholesterol synthesis and absorption, were determined and related to graft histology. When compared to transected controls, auto- and allotransplantation of ileum similarly increased ( P

Enteroendocrine cell-derived peptides modulate postresectional small bowel adaptation, which may be attenuated by transplantation. We investigated whether autotransplantation modulates the number and distribution of ileal enteroendocrine cells in pigs with proximal small bowel resection.Fifteen pigs were assigned into either small intestinal transection or 75% proximal small intestinal resection with or without autotransplantation of the remaining ileum. After 14 weeks the number and subtype distribution of enteroendocrine cells, crypt cell proliferation, and mucosal histology were analyzed from the proximal and distal ends of the remaining ileum.When compared to resected controls, autotransplantation of the ileum decreased the absolute (P0.05 in proximal ileum) and proportional (P0.05 in distal ileum) crypt enteroendocrine cell number. In addition, autotransplantation reduced somatostatin and glicentin expressing cell counts and abolished the proximodistal gradient of the enteroendocrine cell number. When compared to transected controls, villus height, crypt depth, number of proliferating crypt cells, and crypt cell proliferation index increased after the proximal resection (P0.05 in all except in crypt depth and proliferation index of the distal ileum) but remained virtually unchanged after autotransplantation of the ileal remnant.Autotransplantation decreases the crypt enteroendocrine cell number and alters their proximodistal and subtype distribution in the remaining ileum in pigs with proximal small bowel resection. These alterations are associated with attenuated adaptive response of the autotransplanted ileum.

Porcine small bowel allografts were followed for 18 weeks during immunosuppression with cyclosporine-A (CyA), azatioprine and prednisone. The mucosal alterations noted at the 12th week were epithelial vacuolation and loss of Goblet cells. Moderate infiltration of inflammatory cells, mainly lymphocytes, was found in the lamina propria. In addition, a few grafts exhibited oedema and fibrosis. Vessels already showed endothelial swelling and intimal proliferation at the 12th week. In the submucosa, the infiltration of inflammatory cells was not present till the 18th week. Further changes in the mucosa at the 18th week were the blunting of villi, cuboidal epithelium, crypt abscesses and epithelial atrophy. The histological alterations of mucosa and lamina propria existing in the full thickness biopsies were mostly also detectable in mucosal biopsies, provided that multiple biopsies were taken. Thus these parameters analyzed from mucosal biopsy material are suitable for the diagnosis and monitoring of chronic small bowel rejection. In autopsy, the most prominent features were in the mesenterial arteries: intimal proliferation, vasculitis, proliferation of media and endothelial alterations. The activity of the mucosal disaccharidases maltase and sucrase remained near the initial level till the 12th week and had decreased markedly by the 18th week.

Transplantation of the small intestine impairs intestinal absorptive function, but the adaptive response of a segmental graft is unknown. The aim of this study was to investigate the effects of ileal autotransplantation on the adaptive absorption and metabolism of lipids in pigs that had undergone proximal gut resection.Serum lipids, plasma vitamins A and E, absorption and excretion of cholesterol, bile acids and fat, plasma cholesterol precursor and plant sterol proportions to cholesterol (respective markers of cholesterol synthesis and absorption), enteric structure, and transit were determined 4, 8, and 14 weeks after 75% proximal resection with (n = 15) or without (n = 15) autotransplantation of the remaining ileum.As compared with pigs that underwent proximal gut resection, the additional autotransplantation reduced the adaptive increase in total serum and high-density lipoprotein cholesterol, plasma plant sterol proportions and vitamin E concentrations, cholesterol and fat absorption efficiency, and villus height (p0.05 for all) during the 14 postoperative weeks and resulted in increases of up to 4.6, 2.7, 1.3, and 2.1 times the plasma cholesterol precursors (p0.005), fecal excretion of bile acids (p0.0005), neutral steroids (p0.005), and net elimination of cholesterol (p0.0005), respectively. Cholesterol and fat absorption and plasma plant sterols were significantly enhanced between 8 and 14 weeks after autotransplantation (p0.05, p0.005, and p0.05, respectively), whereas fecal elimination of cholesterol remained increased until the end of the follow-up.Autotransplantation of the ileum in pigs that have undergone proximal small bowel resection disturbs the adaptive absorption of cholesterol, bile acids, fat, and fat-soluble vitamins, resulting, through increased fecal elimination of cholesterol, in decreased serum cholesterol despite a marked compensatory increase in cholesterol synthesis.

Our major aim was to investigate the consequences of ileal autotransplantation in pigs with proximal small intestinal resection on biliary lipids and metabolism of bile acids. Biliary lipid secretion rates and bile acid absorption were assessed by measuring dietary and biliary lipids, fractional cholesterol absorption, and fecal excretion of cholesterol and bile acids. In addition, serum bile acids and cholesterol, biliary and fecal bile acid species, and ileal villus height were determined after resection of the proximal 75% of the jejunoileum (n = 15) and autotransplantation of the remaining ileum with systemic venous drainage (n = 15) or transection (n = 5). Autotransplantation further increased fecal excretion of neutral and acidic steroids and serum concentration of bile acids after proximal resection (P < .05 for all); autotransplantation significantly decreased serum cholesterol, ileal villus height, fractional bile acid and cholesterol absorption, and biliary molar percentage of total and primary bile acids, whereas biliary secretion of bile acids, enriched by secondary bile acids, and cholesterol remained unchanged. At 14 weeks, ileal villus height, fractional bile acid and cholesterol absorption, biliary molar percentage of bile acids, and proportion of secondary biliary bile acids were altered by transplantation from the respective postresection values of 864 +/- 22 microm, 97.9 +/- 0.6%, 26.9 +/- 3.9%, 91.8 +/- 1.2% and 9.2 +/- 1.3% to 428 +/- 21 microm, 91.1 +/- 1.5%, 9.5 +/- 1.1%, 83.9 +/- 1.4% and 52.5 +/- 3.5% (P < .005 for all). Posttransplantation biliary bile acid secretion correlated positively with fractional reabsorption (r = .70) and biliary molar percentage (r = .73) of bile acids and ileal villus height (r = .65; P < .01 for all). Decreased absorption efficiency and biliary molar percentage of bile acids, increased biliary secondary bile acids, and short ileal villi point to bacterial overgrowth-induced bile acid malabsorption, which with decreased absorptive area may contribute to malabsorption of other lipids after ileal autotransplantation. Compensatory increase in cholesterol synthesis in the pigs with autotransplanted ileum appeared sufficient for constant biliary secretion of cholesterol and bile acids.