Intestinal glutamine metabolism after massive small bowel resection

Gut glutamine utilization after massive small bowel resection was studied to gain further insight into the alterations and adaptations in intestinal glutamine metabolism that occur during the development of post-resectional hyperplasia. After resection of the middle 60% of the small intestine in the rat, gut glutamine metabolism was studied immediately and 1, 2, and 3 weeks later. Whole gut glutamine extraction was 22% in sham controls and it acutely declined to 12% (p less than 0.01) after bowel resection. Extraction increased to 31% 1 week later (p less than 0.05) and then returned to normal by week 2. Gut ammonia release decreased after massive small bowel resection, whereas intestinal alanine release increased. The increase in gut glutamine extraction at 1 week occurred at a time when jejunal and ileal DNA and protein content were markedly increased (p less than 0.01). Intestinal glutaminase content declined initially and then increased by the third week after bowel resection (p less than 0.01). With time, increases in gut cellularity and glutaminase content are associated with gut glutamine utilization in the shortened small bowel that is equal to that of the intact unresected intestine.     

Glucose and alanine absorption following massive small bowel resection

A 90% small bowel resection in 8 dogs resulted in a significant decrease (p less than 0.05) in D-xylose and D-glucose absorption during the early postoperative period. The absorptive capacity of the residual gut with regard to L-alanine, however, remained unchanged. Anemia and hypoalbuminemia also occurred in time, suggesting a malabsorptive state. Control studies were performed in 8 dogs with small bowel transections. The results suggest that a high protein diet might be of benefit during the early postoperative period after massive small bowel resection.     

Alteration of intestinal intraepithelial lymphocytes after massive small bowel resection

BACKGROUND: Intraepithelial lymphocytes (IEL) comprise the inner most layer of the gut immune system, and play a critical role in protecting the host from enteric organisms. Massive small bowel resection (MSBR) is one such clinical condition where patients are at particularly high risk for the development of such enteric infectious complications. Because of this, we hypothesized that the IEL may change significantly after the formation of a MSBR. To address this, a mouse model of MSBR was created and the acute phenotypic and functional characteristics of the IEL were studied. MATERIALS AND METHODS: Mice underwent a 70% mid-small bowel resection. After 7 days, IEL were isolated and analyzed for phenotypic changes by flow cytometry. IEL cytokine expression was performed with semiquantitative polymerase chain reaction techniques. To assess the functional significance of these changes, IEL proliferative response was assessed in vitro.Results. MSBR led to significant decreases in specific IEL subpopulations: CD 44+ (used as a marker of cell maturity); CD 8alphabeta+ (marker of thymic derivation), and CD 69+ (marker of T cell activation). Compared with controls, IEL TNF-alpha mRNA expression increased 84%, while IL-2 and IL-10 mRNA expression decreased by 69 and 72%, respectively. Spontaneous proliferation of IEL in the MSBR group was significantly higher than controls, however, proliferation failed to increase with T cell stimulation.Conclusion. These changes suggest a shift to a more immature and possibly less activated cell population. It is possible that such alterations may play an important role in the increase in enterically derived infections in patients with MSBR.     

Adverse effects of endotoxin following massive distal bowel resection.

Sepsis is a frequent cause of morbidity following extensive bowel resection. It has been suggested that the lymphoid tissues of the gut may be essential to normal humoral immunity. This study evaluates: (1) the effect of endotoxin on mortality following selective massive bowel resection and jejunoileal bypass; (2) cellular immunity by skin allograft rejection and bypass, and (3) T and B cell lymphocyte subpopulations is mesenteric lymph nodes, intestine and appendix. Endotoxin increased mortality in rats with more distal bowel resection but not following bypass. Skin allograft rejection was similar in each group. Peyer's patches, mesenteric lymph nodes and appendices were evaluated for T & B cell subpopulations. These tissues had a greater percentage of B cells (53% lymph nodes, 63% appendix) with IgM the predominant immunoglobulin. Cellular immunity was not a factor. Lymphoid tissues of the distal bowel and mesentery contain abundant B cells and IgM that may contribute to humoral immunity. Massive bowel resection may increase the risk of morbidity from gram negative sepsis and/or endotoxin presumably due to decreased humoral immunity.     

Long term prognosis after massive small bowel resection in children

Eight survivors after massive small bowel resection were reviewed for a period of 2 to 19 years to assess the long term prognosis of patients. The primary diseases of short bowel syndrome were congenital intestinal atresia (6) and midgut volvulus (2). The length of the residual small intestine ranged between 27 and 75 cm and ileocecal valve was also resected in 3 cases. All cases had been already weaned from parenteral nutrition and six children tolerate normal meals and two have still enteral formula at home now. Near normal somatic growth was achieved in cases which received intensive nutritional supports after operation. The D-Xylose absorption test revealed gradual improvement except one with the shortest intestine (27 cm) and fat absorption was disturbed in patients who had less than 45 cm residual intestine. Late metabolic complications, such as renal calculus, cholelithiasis and pathologic fractures were encountered in three cases.     

Tissue-engineered small intestine improves recovery after massive small bowel resection

OBJECTIVE: Rescue with tissue-engineered small intestine (TESI) after massive small bowel resection (MSBR). SUMMARY BACKGROUND DATA: Short bowel syndrome is a morbid product of massive small bowel resection. We report the first replacement of a vital organ by tissue engineering with TESI after MSBR. METHODS: Ten male Lewis rats underwent TESI implantation with green fluorescent protein (GFP)-marked cells (TESI+, n = 5) or sham laparotomy (TESI-, n = 5) followed by MSBR. Side-to-side anastomosis of TESI to proximal small intestine was performed or omitted. TESIO animals underwent implantation of engineered intestine with no further surgery. Weights were measured QOD until day 40. Transit times were measured. DNA assay was performed with computer morphometry. Northern blots of RNA were probed for intestinal alkaline phosphatase (IAP) and villin. Hematoxylin and eosin, S100, and smooth muscle actin immunohistochemistry were performed. Blood was collected at sacrifice. RESULTS: All 10 rats initially lost then regained weight. The initial rate of weight loss was higher in TESI+ versus TESI-, but the nadir was reached a week earlier with more rapid weight gain subsequently to 98% preoperative weight on day 40 in animals with engineered intestine versus 76% (P < 0.03). Serum B12 was higher at 439 pg/mL versus 195.4 pg/mL. IAP mRNA appeared greater in TESI+ than TESIO, with constant villin levels. Histology revealed appropriate architecture including nerve. GFP labeling persisted. CONCLUSIONS: Anastomosis of TESI significantly improved postoperative weight and B12 absorption after MSBR. IAP, a marker of differentiation in intestinal epithelium, is present in TESI, and GFP labeling was accomplished.     

An experimental evaluation of segmental reversal after massive small bowel resection.

The technique of reversal of a distal segment of residual small intestine was applied to the management of massive resection. A controlled evaluation was carried out in dogs into the effects of segmental reversal on the proximal remnant after the distal 75 per cent of the small bowel had been resected. The variables studied were survival, body weight, glyceryl tri(palmitate-1-14C) absorption and mouth-to-caecum transit time. Animals subjected to resection alone had accelerated intestinal transit, poor absorption, serious weight loss and a high early mortality. It was clearly demonstrated that segmental reversal after resection produced marked and progressive delay in transit time from mouth to caecum, sustained improvement in fat absorption and body weight and enhanced survival.     

Comparison of massive vs. repeated resection leading to short bowel syndrome

Short bowel syndrome can result from either a single massive intestinal resection or repeated lesser resections, which might have prognostic implications. The aim of this study was to compare patient populations and outcome of short bowel syndrome caused by massive and repeated resection. The records of 95 adult patients with short bowel syndrome evaluated over a 20-year period were reviewed. Massive resection was performed in 72 patients (76%) and repeated lesser resections in 23 patients (24%). Patients undergoing massive resection were more likely to be more than 70 years of age (26% vs. 9%, P <0.05). Mesenteric vascular disease was more prevalent among patients undergoing massive resection (39% vs. 9%, P <0.05), whereas Crohn’s disease was less prevalent (1% vs. 35%, P <0.05). Distribution of remnant length, presence of the ileocecal junction, and presence of a stoma were similar. Patients undergoing massive resection were more likely to require parenteral nutrition after the first year (56% vs. 23%, P <0.05). Patients with very short remnants (<60 cm) were more likely to receive parenteral nutrition after massive resection (95% vs. 60%, P <0.05). Thirty-day mortality was higher after massive resection (24% vs. 4%, P <0.05). However, those surviving 30 days had similar survival rates at 1 year and 5 years after massive and repeated resections. Patients undergoing massive vs. repeated resections are different with respect to age, underlying condition, and nutritional support needs. These factors may influence overall outcome in short bowel syndrome. The better nutritional prognosis of patients undergoing repeated resection given similar intestinal remnants may be related in part to enhanced intestinal adaptation. Presented at the Fortieth Annual Meeting of The Society for Surgery of the Alimentary Tract, Orlando, Fla., May 16–19, 1999.     

Morphological and functional changes in the colon after massive small bowel resection

Purpose

Anecdotal evidence suggests that the colon plays an important role after small bowel resection (SBR). However, colonic changes have not previously been studied. The aim of this study was to characterize morphological and functional changes within the colon after SBR and elucidate the influence of diet complexity on adaptation.

Method

In study 1, 4-week-old piglets underwent a 75% SBR or sham operation and were studied at 2, 4, and 6 weeks postoperation to allow analysis of early and late adaptation responses. Piglets received a polymeric infant formula (PIF).In study 2, SBR piglets received an elemental diet and were studied at 6 weeks postoperation and compared with SBR + PIF piglets from study 1. For both studies, immunohistochemistry was used to quantitate intestinal cell types. Changes in functional proteins were measured by Western blot, enteroendocrine/peptide YY (PYY), enterocyte/liver fatty acid binding protein (L-FABP), and goblet cells/trefoil factor 3 (TFF3).

Results

In study 1, early and late adaptation-related changes were observed after SBR. Early adaptation included increased numbers of enterocytes (P = .0001), whereas late adaptation included increased proliferative cell numbers (P = .02). Enteroendocrine, goblet, and apoptotic cells numbers were significantly elevated in the resected group at all time-points studied (P < .05). Functional changes included increased levels of L-FABP (P = .04) and PYY (P = .03). There was no change in TFF3 expression.In study 2, feeding with an elemental diet resulted in suboptimal adaptation as evidenced by reduced rate of weight gain and significant reductions in total cell numbers (P = .0001), proliferative (P = .0001) and apoptotic cells (P = .04), enteroendocrine cells (P = .001), and PYY expression (P .004).

Conclusion

These findings indicate that significant morphological and functional changes occur in the colon after massive SBR and that these occur as early and late adaptation responses. Elemental diet was associated with suboptimal adaptation suggesting an effect of diet complexity on colonic adaptation.     

Bax is required for increased enterocyte apoptosis after massive small bowel resection

BACKGROUND: Massive small bowel resection (SBR) increases rates of both enterocyte proliferation and apoptosis. Previous studies have demonstrated increased intestinal expression of proapoptotic bax mRNA and protein, as well as the appearance of an 18-kd bax cleavage product within 12 hours of SBR. This study tested the hypothesis that bax is required for postresection increases in enterocyte apoptosis. METHODS: Male bax-null and C57Bl/6 (control) mice underwent either a 50% proximal SBR or sham operation. After 3 days, the remnant ileum was harvested and weighed. Apoptotic indexes, proliferation indexes, villus heights, and crypt depths were determined. RESULTS: The usual adaptive increases in ileal wet weight, crypt depth, and rate of proliferation occurred in both the control and bax-null mice. Resection significantly increased the rate of apoptosis in the control mice; however, it failed to alter the apoptotic index in the bax-null mice. CONCLUSIONS: Bax is necessary for the increase in apoptosis that occurs after SBR, but its absence has no significant effect on short-term adaptation. These findings suggest that enterocyte proliferation and apoptosis are differentially regulated during intestinal adaptation.     

Effect of massive small bowel resection on gastric acid secretion in the rat

The phenomenon of a transitory gastric acid hypersecretory state after extensive bowel resection is well established. Its time of onset, however, is unknown. The purpose of this study was to determine the immediate effect of massive small bowel resection (MSBR) on gastric acid secretion (GAS). An anesthetized innervated rat model was prepared with gastric and jugular cannulae. Three groups of animals were studied: group I (n = 12), basal unstimulated state; group II (n = 12), pentagastrin (Pg) 16 micrograms/kg h-1 stimulated; and group III (n = 16), 5% liver extract meal (LEM) stimulated. Each group consisted of experimental animals that underwent 95% MSBR from proximal jejunum to terminal ileum and control animals that remained intact. Acid output was determined by extragastric titration with 0.1 M NaOH. Blood was taken for basal and postprandial serum gastrin levels. Basal acid output (mueq/10 min) significantly increased immediately after MSBR in all groups (p less than .01). Ninety minutes following MSBR, acid outputs were significantly elevated in basal and Pg-stimulated but not LEM-stimulated rats. Serum gastrin increased from 30 +/- 1 to 56 +/- 6 pg/mL (p less than .01) in group I rats and from 81 +/- 28 to 129 +/- 13 pg/mL in group III rats (p = NS). We conclude that GAS increases immediately after MSBR in group I and II rats. This increase in GAS may be mediated by gastrin release.     

The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection

Aims and objectives

Fish oil (FO) lipid emulsion and a new lipid emulsion (SMOF) are important treatments for intestinal failure-associated liver disease. We evaluated the efficacy of FO and SMOF lipid emulsion on intestinal mucosal adaptation using a total parenteral nutrition (TPN)-supported rat model of short bowel syndrome.