Colostrum protein concentrate enhances intestinal adaptation after massive small bowel resection in juvenile pigs

OBJECTIVES: Short bowel syndrome (SBS) usually results from the surgical removal of a large segment of small intestine. Patient outcome depends on the extent of intestinal resection and adaptation of the remaining intestine. We evaluated the impact of colostrum protein concentrate (CPC) on intestinal adaptation after massive small bowel resection in a porcine model of infant SBS. METHODS: Four-week-old piglets underwent an approximate 75% small bowel resection (R, n = 23) or a control transection operation (C, n = 14). Postoperatively, animals from both groups received either pig chow (R = 6, C = 5), polymeric infant formula (R = 6, C = 3) or polymeric infant formula supplemented with CPC (R = 11, C = 6) for 8 weeks until sacrifice. Clinical outcome measures included weight gain and stool consistency. Morphologic measures were intestinal villus height and crypt depth. Functional outcome measure was mucosal disaccharidase activity. RESULTS: Resected animals fed polymeric infant formula alone had reduced weight gain compared with controls fed the same diet (P < 0.005). Despite massive small bowel resection, animals fed pig chow or polymeric infant formula supplemented with CPC grew at an equivalent rate to controls fed polymeric infant formula alone. Resected animals supplemented with CPC had increased villus length and crypt depth in the jejunum (P < 0.001) and ileum (P < 0.001) compared with resected animals fed either pig chow or polymeric infant formula alone. CONCLUSION: In an animal model of SBS, CPC supplementation of polymeric infant formula resulted in normal weight gain and features of enhanced morphologic adaptation.     

Attenuation of rat chronic small bowel allograft rejection by n‐3 polyunsaturated fatty acids is associated with reduced expression of graft IL‐15

Interleukin‐15 was found to play key roles in various immunological processes including chronic rejection after renal and cardiac transplantation. n‐3 polyunsaturated fatty acids (n‐3 PUFA) have shown beneficial effects to chronic allograft rejection. The objective of this study is to search the possible mechanism of this inhibitory effect in chronic small bowel allograft rejection. Animals were divided into three groups: isograft (CsA + corn oil‐supplemented diet); allograft (CsA + corn oil‐supplemented diet); and allograft (CsA + fish oil‐supplemented diet). Donor intestines from F344 rats were transplanted orthotopically into Lewis rat recipients. CsA was administered at 5 mg/kg/day for 2 wk post‐operatively. Post‐transplant weight was recorded. Histopathological changes and graft IL‐15 expression were measured on POD 90. Chronic small bowel allograft rejection developed on POD 90. n‐3 PUFA significantly decreased the score of chronic rejection and increased the post‐operative weight gain rate. This attenuation is associated with reduced graft IL‐15 expression. n‐3 PUFA contributed to improved pathological and clinical outcome during chronic small bowel allograft rejection, and this improvement was associated with reduced graft IL‐15 expression.     

Intraperitoneal fetal small bowel transplantation as therapy for the short bowel syndrome: an animal experimental study.

After demonstration of the morphologic integrity of fetal rat intestinal transplant and in vitro evidence of both digestive and resorptive function in the transplanted small bowel, in another experimental approach we tried to assess intestinal function in vivo. In this experiment, fetal intestinal grafts were placed in host animals and allowed to mature for 4 weeks. Then we resected the whole small bowel of the host from the ligament of Treitz to the ileo-cecal valve, afterwards interposing the matured fetal intestinal segment. A control group of animals (their small bowels were resected but they received no graft replacement) showed massive weight loss. The animals with fetal small bowel transplant replacement thrived. This shows that in the rat model fetal small bowel, previously transplanted into a host, can be an actual functioning substitute for normal small bowel.     

Extensive small intestinal resection in newborn infants

This retrospective study analyzes the management of 83 infants who had undergone extensive small bowel resection as newborns between 1970 and 1987. Resection was performed for atresia (n = 34), volvulus (n = 21), laparoschisis (n = 10), vascular enteropathy (n = 10) and other disorders in 8 cases. The patients were divided into two groups: Group I (33 children) has less than 40 cm and Group II (50 children) 40-80 cm of residual small bowel respectively. Survival depended on the length of residual small bowel (Group I: 63.6%, Group II: 92%) and on their date of birth (born before 1980: 65%, after 1980: 95%). The time required for acquisition of intestinal autonomy depended on the intestinal length (average time, 29.5 months for Group I and 14 months for Group II) and especially on the presence of the ileocecal valve. The residual ileal and/or colon length also influenced adaptation. Artificial parenteral and/or enteral nutrition ensured normal height/weight increases. Home parenteral nutrition allowed children to be returned to their families during intestinal adaptation.     

Intestinal physiology relevant to short-bowel syndrome.

In summary, with resection of the small bowel, the remaining intestine mounts an adaptive response to increase its absorptive surface area. The malabsorption of nutrients is predicated on the importance of the bowel resected to the absorption of a given nutrient. Motor activity is little effected by small-bowel resection. In general, resection of the upper small intestine is better tolerated than resection of the lower small intestine, particularly if the ileocecal junction is affected.     

Bacterial translocation in short-bowel syndrome in rats.

Massive intestinal resection results in short-bowel syndrome (SBS) and is associated with an increased risk of infectious complications mainly caused by the egress of intestinal bacteria to distant organs, a process termed bacterial translocation (BT). The purpose of this experimental study in rats was to investigate in different models of SBS the impact of the type of intestinal resection on bacterial growth in the residual small bowel and on the occurrence of BT. SBS was created in 30 rats either by jejunal resection (JR), by ileal resection (IR) or by ileal resection including the ileocecal valve (IR+ICV). 10 animals underwent only a sham laparotomy (SL) and served as controls. Two weeks after the operative procedure, intestinal bacterial colonization and BT to the portal vein, vena cava, mesenteric lymph nodes, liver and spleen were determined. All resected animals showed a decreased weight gain and a significant bacterial overgrowth in the residual small bowel compared to the SL group. BT occurred after SL in 12%, after JR in 70%, after IR in 58%, and was significantly less frequent (35%) after IR+ICV, respectively. These experimental findings suggest that BT in SBS might be promoted by the intestinal bacterial overgrowth in the residual bowel, and the incidence of BT seems to be related to the presence or absence of the ileocecal valve.     

Ultra-short-bowel syndrome is not an absolute indication to small-bowel transplantation in childhood.

Short-bowel syndrome (SBS) either in adults or in children is considered as an indication to small-bowel transplantation (SBTx), particularly in its most severe form with a residual bowel length below 20 cm. Among factors likely to worsen the prognosis, more recent reports also indicate the number of surgical interventions, early onset sepsis and early development of liver disease. We report six cases of ultra-short-bowel syndrome followed from birth to verify the importance of various prognostic factors. In our case series, the male sex is predominating (5:1). Intestinal resection was indicated in 3 patients for multiple intestinal atresias, in 2 for volvulus and in 1 for necrotizing enterocolitis. The length of intestine remaining was invariably less than 20 cm and 2 patients had a preserved ileocecal valve. In most cases, more than 50% of the colon remained. The number of abdominal operations ranged from 1 to 4. In almost all cases (5 of 6), sepsis and hepatopathy developed early. Our experience suggests that rather than depending on the length of intestine remaining or the presence of the ileocecal valve, the prognosis of patients with the extreme-short-bowel syndrome depends on recurrent neonatal onset sepsis and early onset liver impairment. In addition, our case review shows that the extreme-short-bowel syndrome is not necessarily an indication for bowel transplantation.     

Intranasal versus intravenous administration of midazolam to children undergoing small bowel biopsy

Sixty-three children under the age of 9 years were randomized to receive intravenous (group A, n = 33) or intranasal (group B, n = 30) midazolam as sedation for small bowel biopsy. Mean doses of midazolam given to produce adequate sedation were 0.31 mg (kg body weight)⁻¹ in group A and 0.34 mg (kg body weight)⁻¹ in group B (NS). Four children in group A and 10 children in group B required additional doses to maintain adequate sedation throughout the biopsy procedure (p <0.05). There was no significant difference between the groups regarding the median procedure time (7 min in group A, 8.5 min in group B) or median fluoroscopy time (5 s in group A, 4 s in group B). All children in group B showed signs of discomfort from the nose when given midazolam intranasally. In conclusion, this study indicates that intravenous administration of midazolam is preferable to the intranasal route.     

Does ileal reverse segment in rats with short bowel syndrome change intestinal morphology?

BACKGROUND: The primary goal of surgical therapy for short bowel syndrome is to increase intestinal absorptive capacity. Many surgical procedures have been described for this purpose. One of these is ileal reverse-segment procedure. This procedure after massive small-bowel resection is an alternative way to treat short bowel syndrome, but how it affects intestinal morphology in short bowel syndrome has not been investigated. The aim of this study is to investigate macroscopic and microscopic effects of reverse-segment procedure on the short bowel. METHODS: Twenty rats underwent resection of 80% of the small bowel. The rats were separated into two groups (n = 10). In the first group (reverse group), a reverse segment was formed by twisting a 2-cm ileal segment 180 degrees, without damaging its vascularity. In the second group (control group), a 2-cm ileal segment was resected, preserving its mesentery, and end-to-end anastomosis was performed to maintain the intestinal passage. The segment was not twisted 180 degrees. The 2-cm proximal (jejunal) and distal (ileal) segments of the resected bowel were reserved for histologic investigation. Two months later, the rats were killed and the jejunal and ileal segments were evaluated morphologically. RESULTS: In the reverse group, body weight and total intestinal length significantly increased (14% more than in the control group). The diameter of both proximal (jejunal) and distal (ileal) segments in the reverse group also increased 53.8% and 22.8%, respectively ( P < 0.05). Histologically, crypt depth and villus height of the ileal segment in the reverse group increased 15.2% and 18.2% more than in the control group ( P < 0.05). No histologic change was observed at the jejunal level except for intestinal muscle thickness. CONCLUSIONS: Ileal reverse-segment procedure in rats with short bowel syndrome 1) does not cause intestinal obstruction, 2) increases total bowel length and body weight, 3) increases the diameter of both jejunal and ileal segments, and 4) increases villus height and crypt depth only at the ileal level. For this reason, reverse-segment procedure positively affects intestinal adaptation.     

Long-term outcome of the fetal adrenal gland transplantation in rats.

Three experimental groups have been constructed to evaluate the long-term outcome of fetal adrenal transplantation in rats. In Group 1 (n = 10), rats underwent bilateral adrenalectomy. In Group 2 (n = 10), rats underwent a sham procedure which included flank incision and arterial canulization. In Group 3 (n = 20), a left adrenalectomy was performed followed immediately by transplantation of a fetal adrenal graft into the greater omentum and marked with a prolene suture (Stage 1). One year later, the right adrenal gland of the recipient was removed followed by a determination of the fetal adrenal graft function (Stage 2). Graft function was evaluated by measuring ACTH and corticosterone levels; and a histologic examination of the transplanted fetal adrenal gland was obtained at autopsy. In Group 1, all the rats died within first 8 hours, following bilateral adrenalectomy. In Group 2, and Group 3, all rats survived after Stage 1 operation. During the Stage 2 operation, it was observed that three rats (15%) had neither fetal adrenal transplant nor prolene suture, seven rats (35%) had a well vascularized and developed fetal adrenal graft and a prolene suture. There was no visible fetal adrenal graft but the prolene suture was present in the remaining rats (50%) in Group 3. After removal of the right adrenal gland (6 and 12 hours later), the mean plasma level of ACTH increased with a decline in mean serum corticosterone level in Group 3 compared to the sham-operated animals (p < 0.001). In spite of visible, and viable transplants, all rats died within 48 hours following Stage 2 operation. The mean weight of the fetal adrenal transplant showed a sixteen-fold increase compared to the initial weight (p < 0.001) and histologic examination showed all 3 zones of adrenal cortex, but there were no medullary cells noted. Although the transplanted fetal adrenal grafts survived, their hormonal function was not enough to maintain host viability. Based on these results it is concluded that, insufficiency of the transplanted fetal adrenal gland may be secondary to either graft rejection or suppression of the transplanted tissue by the functional recipient adrenal despite the fetal adrenal transplant survival.     

Progressive perinatal bowel obstruction--a rare cause of short-bowel syndrome.

A girl was born after an uneventful pregnancy of 36 weeks. Prenatally, distended bowel loops had been seen on ultrasound. Multiple small-bowel atresia was diagnosed and treated surgically. In the course of the next eleven weeks, previously patent segments of small bowel became obstructed. In 4 separate operative sessions, several segments of jejunum and ileum were resected, leaving 23 cm of ileum with the ileocecal valve in place. On microscopic examination of all resected material, necrosis of the mucosa was found consistent with ischemia. The child survived and tolerated full enteral feeding at the age of 8.5 months. The origin of the progressive obliterating process remains unknown.     

Somatic growth in infant heart transplant recipients

Infant heart transplantation is now entering its second decade of clinical experience. To understand better issues relating to somatic growth, this retrospective study will describe growth patterns in a group of infant heart transplant recipients. Early growth: growth velocity from birth to transplantation in 77 infants transplanted before 6 months of age was compared with growth velocity from transplant to 3 months. Growth from 3 to 6 months and from 6 to 12 months after transplantation is described. Growth velocities (mean +/- SD) for weight (g/d) and length (cm/yr) for these 4 time periods respectively were: 7+/-14 and 27+/-22, 32+/-9 and 35+/-14, 17+/-7 and 24+/-10, 12+/-6 and 17+/-8. Growth velocities for both weight (p<0.01) and length (p = 0.04) were significantly improved in the first 3 months after transplantation. Late growth: Growth beyond 5 yr post-transplantation was described in a group of 51 infants transplanted in the first year of life and who survived at least 5 yr (median 6.8 yr, range 5.0 to 10.9). Most recent growth parameters (z-score; mean +/- SD) were: weight -0.55+/-1.2, height -0.48+/-0.97 and weight for height -0.16+/-0.96. Factors (with significant p-values) evaluated for their possible influence on late height (<5th percentile vs. > or =5th percentile) were: age at transplant, hospital days from transplant to discharge, hospital days 1st year after transplantation (p = 0.019), hospital days after 1st year, rejection episodes 1st year, rejection episodes 1-5 yr (p = 0.02) mid-parental height (p = 0.008) and isotopic glomerular filtration rate (p = 0.055). Conclusion: Growth while awaiting infant heart transplantation is poor, but adequate catch-up growth does occur. Beyond 5 yr most (88%) infant heart transplant recipients have weight and height in the normal range. Early illness, late rejection and genetic growth potential may play the largest role in later height attainment.     

Effects of supplemental L-arginine on the intestinal adaptive response after massive small-bowel resection in rats

To evaluate whether L-arginine methyl ester (L-Arg) can improve the structure of the small intestine and enhance adaptation in an experimental model of short-bowel syndrome (SBS), 40 Sprague-Dawley rats were divided randomly into four groups of 10 each. In one group only a laparotomy was performed (G1). The remaining 30 rats underwent 90% small-bowel resection (SBR) and formed the three experimental groups: the SBR/untreated group (G2), the SBR/L-NAME-treated group (G3), and the SBR/ L-Arg-treated group (G4). Rats in G2 received no therapeutic treatment. Rats in the SBR/L-NAME and SBR/L-Arg treated groups received N-G-nitro-L-arginine-methyl ester (L-NAME) and L-Arg intraperitoneally for 3 weeks, respectively. The animals were weighed daily. All rats underwent a relaparotomy on day 21 of the experiment. Remnant small bowel was excised and evaluated for villus height and crypt cell mitoses. After the 90% SBR, all animals had from diarrhea and weight loss between the 1st and 6th postoperative days (POD). The body weight of the SBR/L-Arg group showed significant increases at POD 10 and 21 in comparison to the SBR/untreated and SBR/L-NAME groups (P < 0.001). The rats treated with L-Arg had significantly greater villus height and crypt-cell mitoses compared to the other groups (P < 0.0001, P < 0.001). These observations suggest that L-Arg treatment increases villus height and crypt-cell mitoses after massive SBR and may play a considerable role in the mucosal adaptive response in SBS in rats.     

Pharmacologic enhancement of adaptive growth after extensive small-bowel resection

Adaptive hyperplasia, especially of the ileum, is a well-known and extensively studied physiological response that is responsible for the ability of animals to survive extensive small-bowel resection. Luminal nutrients, endogeneous secretions, and humoral factors are considered to be important mediators of this compensatory increase in absorptive surface area. Recently, prostaglandins have been shown to exert a trophic influence on the intestine. The object of this study was to determine whether it is possible to enhance the resection-induced intestinal hyperplasia with a new prostaglandin E₂ (PGE₂) analog (Ro 22–1327). In four groups of rats 4–5 weeks of age, a 70%–80% midintestinal resection was performed. One group (A1) was treated with Ro 22–1327 for 14 days by daily oral gavage; another was treated for 4 weeks (B1). The remaining two groups were used as controls and treated with placebo for 14 days (A2) and 4 weeks (B2). A fifth group was subjected to sham laparotomy without intestinal resection and treatment. In both groups treated for 14 days, relaparotomy was performed on the 14th day and intestinal length and width were measured. Threafter, treatment was discontinued for another 14 days. After 4 weeks the intestinal segments from all animals were removed (jejunal and ileal remnants, cecum, and colon). Lenght, width, and wet and dry weights were measured and surface areas were calculated. The results demonstrate a significant increase in all intestinal parameters in groups treated with the PGE₂ analog. In the small intestine, the trophic response was expressed more in the jejunum. Postresectional adaptive growth in the cecum and colon was also enhanced by Ro 22–1327. The results of this study suggest that trophic substances could be used therapeutically to increase intestinal surface area in patients with short bowel syndrome. Offprint requests to: M. E. HöllwarthSupported by funds from the National Heart Lung and Blood Institute (HL 26441) and Hoffmann-La Roche Inc.     

Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation

Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluate the effect of single and multiple donor-specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty-five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowel transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 x 10(6) cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 10(6) cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 10(6) cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 10(6) cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100% in 0.5 mg/kg and 42.1% in 1 mg/kg FK506 groups). On day 30, 58.3% of bone-marrow-infused animals and 66.6% of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12% after transplant and were significantly higher in bone-marrow-infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short-course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation.     

新生儿暂时性短肠综合征治疗体会

目的 探索肠外营养(parenteral nutrition,PN)对新生儿暂时性短肠综合征(temporary short bowel syndrome,TSBS)患儿造瘘期间的治疗作用,并对防治并发症进行探索.方法 回顾性分析2001年1月至2015年12月在我院PN支持治疗的21例新生儿TSBS患儿的诊疗经过,并对其进行随访.结果 符合入组标准的患儿共21例,所有患儿均在新生儿期因各种原因行高位小肠造瘘术,术后需长期依赖PN.其中男12例,女9例.入院年龄1d至8个月(中位年龄2个月),随访3～140个月,中位随访时间21个月.随访至2015年12月时,存活15例,病死6例;存活组中13例关瘘,2例未关瘘;病死组中2例关瘘,4例未关瘘.经Fisher's Exact检验,病死组患儿均发生并发症,存活组仅5例发生并发症(P=0.012);病死组中3例保留回盲部,存活组中9例保留回盲部,两组间差异无统计学意义.经Studentt检验,病死组存留小肠长度(57.5±14.1)cm,显著短于存活组(115.9±46.7)cm(P=0.008).两组患儿的出生体重及入院时年龄别体重z值无统计学意义.结论 新生儿TSBS患儿存留小肠越短,并发症发生率越高,死亡风险越大.合理营养支持对该类患儿后续治疗意义重大,积极随访对预防、早期发现和治疗相关并发症作用明显.     

A successful short-bowel syndrome model in neonatal piglets.

BACKGROUND: With the higher survival rate of premature neonates as a result of improved neonatal intensive care, the incidence of necrotizing enterocolitis, and thus the incidence of short-bowel syndrome, is increasing. An appropriate animal model resembling the (premature) neonate with short-bowel syndrome suitable for clinically relevant neonatal bowel adaptation and intervention studies, is not available at present. The purpose of this study was the development of a short-bowel syndrome model that mimics the clinical state of the affected neonatal patient. METHODS: Sixteen 7-day-old piglets received either a small bowel transection (group A) or a 75% resection (group B). The piglets were fed 125 kcal/kg body weight per day, including additional electrolytes. The animals were weighed daily and were killed 28 days after surgery. Bowel samples were obtained at both time points. RESULTS: Mortality rates in groups A and B were 0% and 8%, respectively. Body weight gain was significantly higher in group A than in group B (156% vs. 93%; P = 0.01). Jejunal villus length was higher in group B than in group A (74% vs. -2%; P = 0.006), and crypt depth was higher in group B in both jejunum (201% vs. 67%; P = 0.001) and ileum, (197% vs. 20%; P = 0.001), than in group A. CONCLUSIONS: In 7-day-old piglets 75% small bowel resection leads to a clinical short-bowel syndrome, demonstrated by reduced weight gain and typical changes in bowel adaptation parameters. The excellent survival of the animals provides a possibility for the study of bowel adaptation in a neonatal model as well as in intervention studies.     

Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat

Arginine and nitric oxide are critical to the normal physiology of the gastrointestinal tract and maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluate the effects of oral arginine (ARG) supplementation on intestinal structural changes, enterocyte proliferation, and apoptosis following intestinal ischemia–reperfusion (IR) in the rat. Male Sprague–Dawley rats were divided into three experimental groups: sham rats underwent laparotomy and superior mesenteric artery mobilization, IR rats underwent superior mesenteric artery occlusion for 30 min following by 24 h of reperfusion, and IR-ARG rats were treated with enteral arginine given in drinking water (2%) 48 h before and following IR. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h following IR. A nonparametric Kruskal–Wallis ANOVA test was used for statistical analysis with p <0.05 considered statistically significant. IR rats demonstrated a significant decrease in bowel weight in duodenum and jejunum, mucosal weight in jejunum and ileum, and villus height in jejunum and ileum compared with control animals. IR rats also had a significantly lower cell proliferation index in jejunum and ileum and a higher apoptotic index in ileum compared with control rats. IR-ARG animals demonstrated greater duodenal and jejunal bowel weight; duodenal, jejunal, and ileal mucosal weight; and jejunal and ileal cell proliferation index compared with IR animals. In conclusion, oral ARG administration improves mucosal recovery following IR injury in the rat.     

Intra-operative pulse oximetry can help determine intestinal viability

 The intra-operative assessment of intestinal viability when dealing with ischaemic bowel remains a challenge. Reliable healing of small-bowel anastomoses, using pulse oximetry to exclude critical ischaemia, has been shown in the canine model. In this study, intra-operative pulse oximetry (PO) was used to help determine intestinal viability 48 h after de-torsion of a volvulus. Approximately one-half of the ischaemic, volved bowel was able to be preserved. Intra-operative PO can thus help preserve bowel of doubtful viability. Accepted: 10 April 2000     

Lipopolysaccharide endotoxemia reduces cell proliferation and decreases enterocyte apopotosis during intestinal adaptation in a rat model of short-bowel syndrome

Sepsis is frequently associated with or complicates short-bowel syndrome (SBS). To investigate the effects of lipopolysaccharide (LPS) endotoxemia on enterocyte proliferation and death via apoptosis in a rat model of SBS, adult male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis; SBS rats underwent 75% small-bowel resection; and SBS-LPS rats underwent 75% bowel resection and were given intraperitoneal injections of LPS 10 mg/kg. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and death via apoptosis were determined on day 15 after the operation. Statistical analysis was determined by Student's and ANOVA tests with a P less than 0.05 considered significant. SBS-LPS animals demonstrated a significant decrease (vs SBS rats) in duodenal (20%), jejunal (30%), and ileal (15%) overall weight, duodenal (20%), jejunal (27%), and ileal (18%) mucosal weight, jejunal (20%) and ileal (30%) mucosal DNA, jejunal (29%) and ileal (31%) villus height, and jejunal (14%) and ileal (29%) crypt depth. LPS endotoxemia led to reduced cell proliferation and enterocyte apoptosis compared to untreated SBS animals. Thus, in a rat model of SBS, LPS endotoxemia inhibits intestinal adaptation. A possible mechanism may be decreased cell proliferation. Decreased enterocyte loss via apoptosis may reflect a reduced number of enterocytes. Other mechanisms (necrosis) may be mainly responsible for cell death following LPS injection.