Remnant Jejunum Research Articles

Segmental reversal of the distal small intestine in a short bowel syndrome model in piglets showed detrimental effect on weight gain

BackgroundTo investigate the effects of a reversed segment of the distal small intestine to improve weight gain in an experimental short bowel syndrome (SBS) model in piglets.MethodsTwenty-four piglets underwent resection of 70% of the distal small intestine. In half of the animals a conventional anastomosis was performed, and in the other half, the distal 25 cm of the remnant jejunum was reversed before the intestinal continuity was recreated. Weight was measured daily until day 28, where the animals were euthanized. Glucagon-Like Peptide-2 (GLP-2) and Glucose-dependent Insulinotropic Peptide (GIP) was measured pre- and postoperatively at day 28.ResultsThe group with reversal of small intestine had a significant lower weight gain at 5.26 ± 3.39 kg (mean ± SD) compared to the control group with 11.14 ± 3.83 kg (p < 0.05). In the control group greater villus height and crypt depth was found distally, and greater muscular thickness was found proximally in the intervention group. GLP-2 and GIP levels increased significantly in the control group.ConclusionsTreatment of short bowel syndrome with a reversed jejunal segment of 25 cm had a detrimental effect on the weight gain.

Prevalence, Risk Factors, and Complications of Cholelithiasis in Adults With Short Bowel Syndrome: A Longitudinal Cohort Study.

Background: Patients with short bowel syndrome (SBS) are at a high risk of cholestasis or cholelithiasis. This study aimed to determine the incidence, risk factors, and clinical consequences of cholelithiasis in adults with SBS over an extended period.Methods: All eligible adults diagnosed with SBS and admitted to a tertiary hospital center between January 2010 and December 2019 were retrospectively identified from the hospital records database. Kaplan–Meier analysis was used to estimate the cumulative incidence of SBS during the 10-year period. For assessment the risk factors for cholelithiasis, we used multivariate Cox proportional hazards model with estimation of hazard ratio (HR) with 95% confidence intervals (95 %CI).Results: This study enrolled 345 eligible patients with SBS. Kaplan–Meier analysis revealed that 72 patients (20.9%) developed cholelithiasis during the 10-year observation period. In multivariate analyses using the Cox proportional hazard model revealed that the remnant jejunum (HR = 2.163; 95% confidence interval [CI]: 1.156–4.047, p = 0.016) and parenteral nutrition dependence (HR = 1.783; 95% CI: 1.077–2.952, p = 0.025) were independent risk factors for cholelithiasis in adults with SBS. Twenty-eight patients developed symptoms and/or complications in the cholelithiasis group. Proportions of acute cholecystitis or cholangitis and acute pancreatitis were significantly increased in the cholelithiasis group compared with the non-cholelithiasis group (31.9 vs. 7.7%, p < 0.01; and 6.9 vs. 1.1%, p = 0.003, respectively).Conclusion: Because of the adverse clinical consequences of cholelithiasis, adult patients with SBS should be closely monitored, and preventive interventions should be considered.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04867538.

A136 LIVING ON THE EDGE: EUS-DIRECTED TRANSGASTRIC ERCP (EDGE) IN PATIENTS WITH ROUX-EN-Y GASTRIC BYPASS ANATOMY

Abstract Background Roux-en-Y gastric bypass (RYGB) surgery imposes anatomic barriers to endoscopic retrograde cholangiopancreatography (ERCP). Potential options for biliary access in these patients include laparoscopic-assisted ERCP or balloon enteroscopy. However, these approaches require specialized equipment and/or operating room personnel and are associated with high rates of failure and adverse events compared to conventional ERCP. A recently described technique, EUS-directed transgastric ERCP (EDGE), is an entirely endoscopic approach which involves accessing the excluded stomach to facilitate conventional ERCP. Objectives To describe the results of EDGE procedures performed in two centres in British Columbia. Aims To describe the results of EDGE procedures performed in two centres in British Columbia. Methods Data were collected from five patient cases who had undergone an EDGE procedure at Victoria General Hospital (4) or Vancouver General Hospital (1) in British Columbia from 2019 to 2020. All patients had a history of RYGB bariatric surgery. In each of the procedures, a 20 mm diameter lumen-apposing metal stent (LAMS) was deployed under EUS-guidance to allow access from the gastric remnant or proximal jejunum to the excluded stomach. Subsequently, during a separate procedure 4 to 28 days later, a duodenoscope was passed through the LAMS to perform ERCP. Following ERCP, the LAMS was removed 0 to 38 days later and replaced with a double pigtail stent to facilitate controlled closure of the gastro-jejunal or gastro-gastric fistula. Results Of the five cases included in the case series, 4 patients underwent EDGE for treatment of choledocholithiasis and one patient underwent the procedure for gallstone pancreatitis. The technical success rate of the EDGE procedure in the five cases was 100%. Clinical success, defined by normalization of bilirubin and symptomatic relief, was observed in all of the cases. There were no adverse events related to the EDGE procedure in these five cases. Conclusions The results of this series support EDGE as a safe and minimally invasive approach to biliary access and therapy in patients with previous RYGB surgery. Funding Agencies None

Evaluation of a Modified Jejunoileal Bypass Technique (Lazzarotto and Souza Procedure): Causes of Reversal and Types of Possible Procedures

Obesity became a pandemic according to WHO in a world where more than one billion people are classified as overweight or obese. Many procedures have been developed in the past years, some of them were effective, while others caused major side effects and morbidity to patient. Lazzarotto and Souza procedure is modified jejunoileal bypass in which a silastic ring is placed at the remnant jejunum to control the amount of food content reaching the bypassed small bowel. This is a retrospective evaluation of data collected from two hospitals located in Curitiba, Parana state, 21 patients underwent Lazzarotto and Souza procedure from year 2002 to 2014. Here we present the results and outcomes of these patients.

Differential action of TGR5 agonists on GLP-2 secretion and promotion of intestinal adaptation in a piglet short bowel model.

Enteroendocrine L cells and glucagon-like peptide 2 (GLP-2) secretion are activated in the intestinal adaptation process following bowel resection in patients with short bowel syndrome. We hypothesized that enteral activation of Takeda G protein-coupled receptor 5 (TGR5), expressed in enteroendocrine L cells, could augment endogenous GLP-2 secretion and the intestinal adaptation response. Our aim was to assess the efficacy of different TGR5 agonists to stimulate GLP-2 secretion and intestinal adaptation in a piglet short-bowel model. In study 1, parenterally fed neonatal pigs (n = 6/group) were gavaged with vehicle, olive extract (OE; 10 or 50 mg/kg), or ursolic acid (UA; 10 mg/kg), and plasma GLP-2 was measured for 6 h. In study 2, neonatal pigs (n = 6-8/group) were subjected to transection or 80% mid-small intestine resection and, after 2 days, assigned to treatments for 10 days as follows: 1) transection + vehicle (sham), 2) resection + vehicle (SBS), 3) resection + 30 mg UA (SBS + UA), and 4) resection + 180 mg/kg OE (SBS + OE). We measured plasma GLP-2, intestinal histology, cell proliferation, and gene expression, as well as whole body citrulline-arginine kinetics and bile acid profiles. In study 1, GLP-2 secretion was increased by UA and tended to be increased by OE. In study 2, SBS alone, but not additional treatment with either TGR5 agonist, resulted in increased mucosal thickness and crypt cell proliferation in remnant jejunum and ileum sections. SBS increased biliary and ileal concentration of bile acids and expression of inflammatory and farnesoid X receptor target genes, but these measures were suppressed by UA treatment. In conclusion, UA is an effective oral GLP-2 secretagogue in parenterally fed pigs but is not capable of augmenting GLP-2 secretion or the intestinal adaptation response after massive small bowel resection. NEW & NOTEWORTHY Therapeutic activation of endogenous glucagon-like peptide 2 (GLP-2) secretion is a promising strategy to improve intestinal adaptation in patients with short bowel syndrome. This study in neonatal pigs showed that oral supplementation with a selective Takeda G protein-coupled receptor 5 (TGR5) agonist is an effective approach to increase GLP-2 secretion. The results warrant further study to establish a more potent oral TGR5 agonist that can effectively improve intestinal adaptation in pediatric patients with SBS.

PP261-SUN: Outstanding abstract: Calorie Requirements of Chronically Ventilated, Brain Impaired Children

and circumference (10.7±0.9mm vs. NS 8.5±0.9mm and LCT 9.0±0.9mm, p < 0.001). Although there were no differences in jejunal length, villus height, villus width or crypt width, mucosal-to-serosal amplification ratio calculations revealed greater jejunal mucosal surface area with MCT (327±77cm2 vs. NS 193±85cm2 and LCT 215±40cm2, p < 0.01). Conclusion: MCT appear superior to NS and LCT in increasing jejunal gross morphology and mucosal surface area after massive ileocecal resection, independent of enteric hormones. It remains to be determined whether MCT can stimulate functional adaptation of remnant jejunum in SBS.

PP262-SUN: The Role of Interleukin-6 Gene 572 G/C Polymorphism in Child Obesity

and circumference (10.7±0.9mm vs. NS 8.5±0.9mm and LCT 9.0±0.9mm, p < 0.001). Although there were no differences in jejunal length, villus height, villus width or crypt width, mucosal-to-serosal amplification ratio calculations revealed greater jejunal mucosal surface area with MCT (327±77cm2 vs. NS 193±85cm2 and LCT 215±40cm2, p < 0.01). Conclusion: MCT appear superior to NS and LCT in increasing jejunal gross morphology and mucosal surface area after massive ileocecal resection, independent of enteric hormones. It remains to be determined whether MCT can stimulate functional adaptation of remnant jejunum in SBS.

Dietary fish oil increases fat absorption and fecal bile acid content without altering bile acid synthesis in 20-d-old weanling rats following massive ileocecal resection

Dietary fish oil (FO) was reported to lower fecal fat excretion in a weanling rat model of short bowel syndrome (SBS) after ileocecal resection (ICR), and to induce changes in secretion and synthesis of bile acid (BA) in adults. We hypothesized that dietary FO, as compared with corn oil (CO), increases intestinal fat absorption in weanling SBS rats in part due to increased hepatic BA synthesis and luminal BA concentrations. After undergoing ICR, 20-d-old rats were fed ad lib for 7 d with a CO or FO diet containing 5% sucrose polybehenate (SPB), a marker for dietary fat absorption. Fecal fatty acid, fecal and intestine luminal BA, liver mRNA expressions of cholesterol 7α-hydroxylase (Cyp7α1) and sterol-12α-hydroxylase (Cyp8β1), and serum 7α-hydroxy-4-cholesten-3-1 (7αC4) levels were determined. As compared with CO-ICR rats, FO-ICR rats had higher intestinal absorption of total fat and most individual fatty acids. Although the BA content per gram of dry stool was increased in FO-ICR rats, there were no differences between groups for the BA content in remnant jejunum, liver mRNA expression of BA biosynthetic enzymes, Cyp7α1 and Cyp8β1, or serum 7αC4, a marker for BA synthesis. Dietary FO increases dietary fat absorption without increasing hepatic BA synthesis in weanling SBS rats.

Ursodeoxycholic acid promotes intestinal adaptation in a cat model of short bowel syndrome

The aim of this study was to assess the effect of ursodeoxycholic acid (UDCA) on the morphological and functional adaptive response of the jejunal remnant after massive intestinal resection in a cat model of short bowel syndrome (SBS). UDCA was administered to animals at a daily oral dose of 15 mg/kg for 6 weeks following a 85% jejunoileal resection. Resection alone caused extensive hyperplasia of jejunal mucosa, as evidenced by a significant increase in the weight of jejunal mucosa per unit length as well as by significant increases in DNA and protein concentration but no change in the protein/DNA ratio. Morphometric analysis using microscopy revealed no changes in jejunal mucosa thickness, jejunal crypt depth, villus height and villus surface area, although villus thickness was increased. The specific activities of jejunal sucrase and alkaline phosphatase were unaffected. UDCA treatment of resected animals, using doses that caused no toxicity, as evidenced by the absence of serum biochemistry abnormalities and histopathology, did not induce, compared to resection alone, any changes in mucosal cellularity and did not affect villus morphometry. On the other hand, UDCA administration increased crypt depth and, also, induced a profound increase in the specific activity of sucrase. UDCA improved diarrhoea, a core SBS symptom, reflected in a considerably reduced frequency of defaecation and improved form and texture of faeces. It is concluded that UDCA administration may enhance the natural adaptive response of the intestinal remnant following massive jejunoileal resection and may, thus, be beneficial in SBS treatment.

The relationship between intestinal histology and function as shown by compensatory enlargement of remnant villi after midgut resection in chickens

To demonstrate the relationship between intestinal histology and function, we investigated the possibility that compensatory enlargement of villi in the chickens' remnant intestine can be induced after 50% or 80% jejunal resection as well as after 50% jejunal plus 70% ileal resection. Compared with intact control chickens, operated chickens showed an almost similar body weight, nitrogen retention, and ether extract digestibility, an improved dry matter digestibility, and a much greater absorption of protein and ether extract by the remnant jejunum and ileum. This suggests an enhanced absorptive function of the remnant intestine. In these chickens, increased value of most light microscopic parameters, increased frequency of anastomosing of each villus, and increased number of protuberated epithelial cells appeared with an increase in the intestinal resection area. This suggests that intestinal villi and epithelial cells are hypertrophied in the remnant jejunum and ileum, and that intestinal villi adapt to activated intestinal absorptive function not by increasing their numbers, but by fusing together into larger villi. These findings demonstrate that intestinal histology is intimately related to intestinal function.

Diurnal expression of the rat intestinal sodium–glucose cotransporter 1 (SGLT1) is independent of local luminal factors

The intestinal sodium-glucose cotransporter 1 (SGLT1) is responsible for all secondary active transport of dietary glucose, and it presents a potential therapeutic target for obesity and diabetes. SGLT1 expression varies with a profound diurnal rhythm, matching expression to nutrient intake. The mechanisms entraining this rhythm remain unknown. We investigated the role of local nutrient signals in diurnal SGLT1 entrainment. Male Sprague-Dawley rats, which were acclimatized to a 12:12 light:dark cycle, underwent laparotomy with formation of isolated proximal jejunal loops (Thiry-Vella loops). Animals were recovered for 10 days before harvesting at 4 6-h intervals (Zeitgeber times ZT3, ZT9, ZT15, and ZT21, where ZT0 is lights on; n = 6-8). SGLT1 expression was assessed in protein, and mRNA extracts of mucosa were harvested from both isolated loops (LOOP) and remnant jejunum (JEJ). Isolated loops were healthy but atrophic with minimal changes to villus architecture. A normal anticipatory rhythm was observed in Sglt1 transcription in both LOOP and JEJ, with the peak signal at ZT9 (2.7-fold, P < .001). Normal diurnal rhythms were also observed in the protein signal, with peak expression in both LOOP and JEJ at ZT9 to 15 (2.1-fold, P < .05). However, an additional more mobile polypeptide band was also observed in all LOOP samples but not in JEJ samples (61 kDa vs 69 kDa). Enzymatic deglycosylation suggested this to be deglycosylated SGLT1. The persistence of SGLT1 rhythmicity in isolated loops indicates that diurnal induction is independent of local luminal nutrient delivery, and it suggests a reliance on systemic entrainment pathways. However, local luminal signals may regulate glycosylation and, therefore, the posttranslational handling of SGLT1.

Glucagon-like Peptide-2 Induces a Specific Pattern of Adaptation in Remnant Jejunum

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 microg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2's effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2's effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.

Weight loss and morphometric study of intestinal mucosa in rats after massive intestinal resection: influence of a glutamine-enriched diet

Short-bowel syndrome is responsible for significant metabolic alterations that compromise nutritional status. Glutamine is considered an essential nutrient for enterocytes, so beneficial effects from supplementation of the diet with glutamine are hypothesized. In this study, the effect of a diet enriched with glutamine was evaluated in rats undergoing extensive small bowel resection, with analysis of postoperative weight loss and intestinal morphometrics of villi height, crypt depth, and thickness of the duodenal and remnant jejunal mucosa. Three groups of male Wistar rats were established receiving the following diets: with glutamine, without glutamine, and the standard diet of laboratory ration. All animals underwent an extensive small bowel resection, including the ileocecal valve, leaving a remnant jejunum of only 25 cm from the pylorus that was anastomosed lateral-laterally to the ascendant colon. The animals were weighed at the beginning and end of the experiment (20th postoperative day). Then they were killed and the remnant intestine was removed. Fragments of duodenal and jejunal mucosa were collected from the remnant intestine and submitted to histopathologic exam. The morphometric study of the intestinal mucosa was accomplished using a digital system (KS 300) connected to an optic microscope. Morphometrics included villi height, crypt depth, and the total thickness of intestinal mucosa. The weight loss comparison among the 3 groups showed no significant loss difference. The morphometric studies showed significantly taller duodenal villi in the glutamine group in comparison to the without glutamine group, but not different from the standard diet group. The measurements obtained comparing the 3 groups for villi height, crypt depth, and thickness of the remnant jejunum mucosa were greater in the glutamine-enriched diet group than for the without-glutamine diet group, though not significantly different from with standard-diet group. In rats with experimentally produced short-bowel syndrome, glutamine-enrichment of an isonitrogenous test diet was associated with an improved adaptation response by the intestinal mucosa but not reduced weight loss. However, the adaptation response in the group receiving the glutamine-enriched diet was not improved over that for the group fed regular chow.

Oral feeding maintenance after intestinal resection: Adaptive response to insert remnant jejunum in colon

Oral feeding maintenance after intestinal resection: Adaptive response to insert remnant jejunum in colon

Ileal resection enhances jejunal absorptive adaptation for water and electrolytes to extrinsic denervation: Implications for segmental small bowel transplantation

Background/Purpose: Segmental small bowel transplantation (SBT) may be an alternative to whole jejunoileal SBT. The aim of this study was to evaluate adaptability of extrinsically denervated jejunum after ileectomy. Methods: Baseline absorption of an isomolar, nonnutrient electrolyte solution was measured in an 80-cm in situ jejunal segment. Control (CON) and extrinsically denervated dogs (EXT DEN) then underwent distal 50% enterectomy; EXT DEN dogs also underwent a complete extrinsic denervation of remnant jejunum. Absorption was remeasured 2 and 12 weeks later; jejunal biopsies at 12 weeks were compared with baseline. Results: All dogs experienced weight loss and diarrhea, which resolved by 10 weeks in CON but persisted in EXT DEN dogs. Net absorptive fluxes of water, Na+, K+, and Cl−, however, remained unchanged in both groups 2 weeks and 12 weeks after denervation. Morphometric evaluation showed an increase in crypt depth in both groups at the 12-week time-point. Conclusions: Despite a clinical short bowel syndrome, more weight loss, and diarrhea in EXT DEN, there were no temporal differences in net absorptive fluxes of water and electrolytes within or between these 2 groups, and both developed increased crypt depth at 12 weeks. Extrinsic denervation does not blunt jejunal adaptive response to ileectomy. J Pediatr Surg 38:502-507. Copyright 2003, Elsevier Science (USA). All rights reserved.

Epidermal growth factor improves nutritional outcome in a rat model of short bowel syndrome

Background/Purpose: This study investigates the effect of epidermal growth factor (EGF) on nutrient absorption in a rat model of short bowel syndrome (SBS). Methods: Male juvenile rats underwent either transection (Sham) or ileocecal resection leaving a 20-cm jejunal remnant. Animals underwent follow-up for 10 days, and resected animals were treated with placebo or recombinant human EGF (1-53). Animals were pair fed; in vivo nutrient absorption, intestinal permeability, morphology, and total intestinal DNA and protein content were measured. Results: Resected EGF-treated animals lost significantly less weight than those in the placebo group (−4.2 ± 3 v −13.7 ± 6.9%), absorbed significantly more 3-0 methylglucose (76.8 ± 6.6 v 64.9 ± 10.1%), and had reduced permeability (lactulose/mannitol ratio, 0.35 ± 0.19 v 0.60 ± 0.20; P <.05 for all comparisons). Conclusions: These findings show that treatment of short bowel syndrome animals with EGF reduced weight loss and improved carbohydrate absorption and intestinal permeability. These findings suggest that enteral EGF may be a useful therapy for short bowel syndrome; further studies are indicated. J Pediatr Surg 37:765-769. Copyright 2002, Elsevier Science (USA). All rights reserved.

Systemic GLP-2 levels do not limit adaptation after distal intestinal resection

Background/Purpose: Glucagonlike peptide 2 (GLP-2) is trophic for the small bowel; it is produced by L cells in the distal intestine in response to luminal nutrients. This study tests the hypothesis that distal small bowel and cecal resection would decrease GLP-2 levels and reduce adaptation. Methods: Male Sprague-Dawley rats (200 to 300 g) underwent either ileal transection (controls) or resection of the ileum and cecum, leaving 10 or 20 cm jejunal remnant anastomosed to the ascending colon. Animals were followed up for up to 21 days. Endpoints were daily weights, intestinal histology, in vivo absorption of 3-0 methylglucose (a measurement of active nutrient absorptive capacity), and serum GLP-2 levels. Results: The control group had a maximum 6% weight loss around day 2, and then recovered with a steady weight gain. The 10-cm jejunal remnant group lost weight continuously and never recovered postsurgery. The 20-cm jejunal remnant group of animals had a maximum of 12% weight loss by day 4 and then slowly gained weight. The average villus height increased significantly (P <.01) in the 10-cm and 20-cm jejunal remnant groups compared with controls. Absorption of 3-0 methylglucose was significantly decreased (P <.01) in both resected groups. Serum GLP-2 levels were increased significantly (P <.05) when compared with controls in both resection groups. Conclusions: Increased serum GLP-2 levels were found in the ileocecal resection rat model, and these levels correlated with morphologic adaptation. However, this morphologic adaptation was not sufficient to restore nutrient absorption as shown by weight changes and 3-0 methylglucose absorption. Thus, the original hypothesis of this study is incorrect: systemic GLP-2 levels do not limit adaptation following distal ileocecal resection. J Pediatr Surg 36:750-754. Copyright © 2001 by W.B. Saunders Company.

Evaluation of the longitudinal musculature of segments of the distal colon interposed following extended jejunum-ileum resection.

Several morbid conditions may necessitate extensive intestinal resection, leading to short-bowel syndrome. When clinical treatment becomes inefficient, a surgical approach is necessary. Distal colon interposition is one of the viable techniques. The interposition of colon segments between remnants of the small bowel improved lifestyle, increased transit time, and diminished diarrhea. The aim of this study is to observe the longitudinal muscular contractions after distal colon interposition. Sixteen male Wistar rats (EPM-1) were submitted to an 80% small bowel resection associated with a partial colectomy of the distal colon immediately after the bifurcation of the middle colic artery followed by a 3-cm isoperistaltic distal colon interposition. After 70 days, the animals were submitted to euthanasia and segments of the jejunum, ileum, remnant colon, and interposed colon were prepared for pharmacological tests. The isometric contractions were measured by a polygraph. After 30 minutes, the dose/effect curves were obtained for both metacholine and barium chloride stimulation through the extraluminal surface (serosa). After this period, we observed a significant increase in the length, diameter, and thickness of the intestinal wall. Regarding the sensibility (pD(2)), no difference was found (interposed colon = 7.21 +/- 0.2; remnant colon = 7.65 +/- 0.1; remnant jejunum 7.46 +/- 0.1; and remnant ileum 7.57 +/- 0.1), even though the animals were submitted to different procedures. In relation to the maximal effect (E(max)), the longitudinal muscle contraction responses (interposed colon = 11.79 +/- 0.1; remnant jejunum = 15.42 +/- 0.2; and remnant ileum = 11.48 +/- 0.2) were lower than those of the remnant colon (E(max) = 22.42 +/- 0.1). This means that there was a possible adaptation of colonic segments to their new location.

Factors affecting outcome following proximal and distal intestinal resection in the dog: an examination of the relative roles of mucosal adaptation, motility, luminal factors, and enteric peptides.

In the clinical setting, resection of the ileum results in an inferior functional outcome compared to jejunal resection. This may be related to a greater adaptive capacity of the ileum, intrinsic structural and functional differences, or regional differences in motor and hormonal function. Our aim was to evaluate the relative contributions of these factors to functional outcome after resection of the proximal or distal intestine. Twenty-four dogs underwent either intestinal transection or 50% resection of the proximal or distal intestine. Studies (nutritional status, absorption, adaptation, motility, peptide levels) were performed every four weeks until the animals were killed at 12 weeks. Caloric intake was similar in all four groups. Weight loss was greater and more sustained after distal resection (DR). Serum cholesterol levels decreased significantly only in the DR group. While stool weight and moisture were similar, the DR animals had persistent, significant steatorrhea. Intraluminal anaerobic bacteria and SCFA concentrations were significantly greater in the ileum but were not influenced by resection. Intestinal remnant length increased to a greater extent after proximal resection (PR), but circumference increased to a similar extent after both resections. Villus height and crypt depth increased significantly only after PR. MMC frequency was similar in all four groups. In the DR animals 26% of migrating motor complexes (MMCs) originated within the remnant. The jejunal remnant of these animals had a dominance of cluster activity similar to the intact distal ileum. Following PR, the postprandial motilin response was decreased. After DR, there were transient increases in neurotensin and PYY. Of the various factors evaluated, mucosal adaptation and the intestinal motor response appear most likely to explain the inferior nutritional and absorptive outcome associated with resection of the distal small intestine.

Depressed smooth muscle contractility after massive intestinal resection in rat: role of alterations in muscarinic receptor status or source of calcium for excitation-contraction coupling.

Following massive intestinal resection (removal of 75% of the mid-jejunoileum) in the rat, there is a significant reduction in the in vitro tonic contractile response of the remaining jejunal circular smooth muscle in response to stimulation with the muscarinic agonist bethanechol. The aim of these experiments was to determine if this alteration is specific to muscarinic excitation and occurs as a result of changes in the source and availability of calcium required for excitation-contraction coupling, or reflects changes in muscarinic receptor number and (or) affinity. The contractile response of proximal jejunal circular muscle strips from sham-operated and resected rats was studied in vitro in response to electrical field stimulation, serotonin, and bethanechol, the later under conditions where extracellular calcium was absent or entry was excluded. In contrast with the significant reduction in tonic contractile response to muscarinic excitation of tissues from resected animals, there was an equivalent or enhanced response of these tissues to electrical field stimulation and serotonin, respectively. While sham-operated and resected groups showed similar dependency upon or availability of intracellular and extracellular calcium, the data indicate distinct pathways of calcium mobilization for tonic versus phasic contractile activity. Muscarinic receptor number and affinity were assessed by 1-quinuclidinyl[pheny1-4-3H]benzilate ([3H]QNB) binding to isolated smooth muscle cells and showed a significant increase in Bmax, with no change in Kd after resection. Thus, the reduced contractility of the circular muscle of the remnant jejunum after massive intestinal resection is a specific even associated with muscarinic receptor activation, but it is not the result of either an alteration in the source or availability of calcium required for excitation-contraction coupling or a reduction in the number and (or) affinity of muscarinic receptors.