El síndrome de intestino corto en el ámbito experimental: experiencia de 15 años / Short bowel syndrome in the research setting: 15 year´experience

En el manejo de pacientes pediátricos con síndrome de intestino corto (SIC), la lucha contra la infección y la hepatopatía asociada a la nutrición parenteral (NP), son seguramente algunos de los aspectos más problemáticos. En la Unidad Experimental del Hospital Donostia llevamos investigando durante los últimos 15 años diferentes formas de reducir estas complicaciones en un modelo de intestino corto experimental en la rata Wistar (resección del 80% del intestino delgado con o sin NP). Todos los experimentos duraron 10 días y 323 animales llegaron al final del periodo de estudio. Se diseñaron 9 grupos que recibieron algún tipo de intervención y 8 grupos control. Las intervenciones fueron tres dietéticas (nutrición enteral mínima [NEM] y probióticos a dosis baja y alta), cinco farmacológicas (administración de hormona de crecimiento [GH], factor de crecimiento epidérmico [EGF],insulina, colecistoquinina [CCQ] y descontaminación intestinal selectiva[DIS]) y una quirúrgica (resección de la válvula ileocecal).La infección en forma de translocación bacteriana (TB) se detectó cultivando los ganglios linfáticos mesentéricos, sangre portal y sangre periférica, y el daño hepático, por los niveles de citoquinas proinflamatorias (..) (AU)

The fight against infection and liver disease associated with parenteral nutrition (PN) are surely two of the most problematic aspects in the management of paediatric patients with short bowel syndrome (SBS).In the Research Unit of Donostia Hospital, we have spent the past 15years investigating different ways of reducing these complications in an experimental model of short bowel in the Wistar rat (resection of80% of the small bowel, with and without PN). All the experiments had a duration of 10 days and 323 animals reached the end of the study period. Nine groups were established in which some type of intervention was performed, and there were 8 control groups. The interventions were:3 dietary (minimal enteral nutrition [MEN] with low or high dose probiotics);5 pharmacological (administration of growth hormone [GH],epidermal growth factor (..) (AU)

Síndrome do intestino curto e transplante intestinal: modelo experimental porcino / Of short bowel syndrome and intestinal transplantation: experimental porcine model

Para melhor compreender as alterações hidro-eletrolíticas, metabólicas e nutricionais em animais de grande porte submetidos a ressecções intestinais extensas e transplante intestinal, propusemos o presente estudo no intuito de se estabelecer um modelo experimental para a Síndrome do Intestino Curto e transplantes intestinais em suínos. MÉTODO: Quarenta e dois porcos Landrace - Large White foram ressecados e divididos em cinco grupos: Grupo 1 (n igual 6) 80% ressecção intestinal; Grupo 2 (n igual 6), ressecção intestinal total; Grupo 3 (n igual 6) ressecção intestinal total e de cólon parcial incluindo válvula ileocecal; Grupo 4 (n igual 7) ressecção intestinal total e transplante intestinal sem imunossupressão e Grupo 5 (n igual 5) ressecção intestinal total e transplante intestinal com utilização de tacrolimo e micofenolato de sódio como imunossupressores. O tacrolimo foi administrado por via oral na dose de 0,2 mg/kg/dia e o micofenolato sódico na dose de 15 mg/kg/dia. O nível sérico do tacrolimo foi ajustado para 15-20 ng/ml. O tempo de acompanhamento dos grupos 1 e 2 foi de 84 dias, enquanto nos grupos 3, 4 e 5 foi de aproximadamente 3 semanas. A avaliação pós-operatória incluiu peso semanal, avaliação clinica e análise bioquímica (sódio, potássio, cálcio, glicemia, uréia, creatinina, triglicérides, colesterol total, proteínas totais, albumina e leucograma). Foi realizada endoscopia convencional com biópsia de enxerto semanal para avaliar a rejeição. RESULTADOS: Grupo 1 ganhou peso corpóreo sugerindo adaptação intestinal, os grupos 2 e 3 perderam peso mostrando inadequada adaptação à ressecção intestinal. Os porcos do grupo 4 e 5 morreram de rejeição celular aguda grave e sepse, respectivamente. Só 1 animal no grupo 5 foi à óbito por intussuscepção. A sobrevivência total em grupos 1, 2, 3, 4 e 5 no dia 30 foi 100%, 100%, 0%, 0% e 20%, respectivamente. A sobrevivência mediana no grupo 4 e 5 foi 14 e 16 dias, respectivamente...

Effect of venous strangulation obstruction on length of equine jejunum and relevance to small-intestinal resection.

OBJECTIVE: To determine if venous strangulation obstruction (VSO) of the distal half of the equine small intestine would increase length of that segment. STUDY DESIGN: Halothane-anesthetized horses were assigned randomly to 3 groups of 5 horses: Group 1 (controls)--the entire small intestine was measured and rubber-shod clamps were applied to mark each end of the most distal 50% of the small intestine; Group 2--same procedure, except that VSO was induced in the distal 50% of the small intestine for 180 minutes; and Group 3--same initial procedure, except that VSO was induced for 90 minutes and followed by reperfusion for 90 minutes. ANIMALS OR SAMPLE POPULATION: Fifteen horses. METHODS: The proximal and distal halves of the small intestine were measured before and at 180 minutes after clamps and ligatures were applied. At the end of the study, biopsies were taken to assess mucosal epithelial damage by light microscopy, and horses were euthanatized while under general anesthesia. RESULTS: Intestine subjected to VSO and VSO and reperfusion had marked hemorrhagic changes and thickening in the intestinal wall. Both groups had incurred a grade 2.8 of 5 mucosal injury by 180 minutes. Total length of small intestine and length of the distal 50% did not change in the control group, but intestine subjected to VSO only and VSO and reperfusion had increased in length by 29% (P <.05) and 36% (P <.05), respectively. CONCLUSIONS: Small intestine of horses subjected to VSO can increase in length, and this change could cause an overestimate of the amount of intestine involved in an extensive strangulating lesion. CLINICAL RELEVANCE: An overestimate of the amount of intestine involved in an extensive strangulating lesion could lead to an overly pessimistic assessment of a horse's risk for postresection malabsorption and maldigestion. Therefore, estimates of the proportion of small intestine that is strangulated should be corrected for this potential error and the risk of malabsorption determined accordingly.

Keratinocyte growth factor enhances early gut adaptation in a rat model of short bowel syndrome.

OBJECTIVE: To evaluate the effects of keratinocyte growth factor (KGF) on intestinal adaptation after resection of 85% of the small intestine and consider its potential application in short bowel syndrome (SBS). STUDY DESIGN: Experimental study using a known model of SBS. ANIMAL POPULATION: Thirty male Sprague Dawley rats. METHODS: Four groups of animals were designated. Two groups underwent 85% resection of the small intestine, while the other two groups were sham-operated, undergoing transection and reanastomosis. Resected and sham-operated groups then received either 3 mg/kg KGF or vehicle subcutaneously daily for 3 days. Gut adaptation was evaluated by measurements of mucosal cellularity and biochemical activity in duodenal, jejunal, and ileal segments. RESULTS: Significant small intestinal growth after bowel resection alone was confirmed in resected versus sham-operated rats. KGF further augmented this growth in the resected animals. Mucosal wet weight of the small intestine increased with resection and was further increased (by 20% or more) with KGF administration. Mucosal thickness, villus length, and crypt depth exhibited similar patterns of response. The KGF-induced increase in mucosal morphology was accompanied by increased mucosal DNA and protein content, followed by a trend toward increased mucosal enzyme activity. Histology demonstrated an increase in goblet cells in KGF-treated animals. In situ hybridization analysis demonstrated that KGF markedly increased mucosal expression of intestinal trefoil protein (ITF) mRNA. CONCLUSIONS: KGF enhances gut growth, differentiation, and gene regulation during adaptation in rat small intestine after massive resection. CLINICAL RELEVANCE: KGF may be beneficial in the management of veterinary and human patients undergoing massive intestinal resection.

Short-bowel syndrome in four dogs.

Short bowel syndrome occurred in four dogs after extensive (74% to 88%) small intestinal resection. Weight loss and diarrhea were the principal clinical signs. Treatment was based on the severity of clinical signs. One dog is alive after 27 months. Three dogs died within 3 months. The prognosis depends on the extent and site of resection, degree of intestinal adaptation, preoperative condition, and postoperative care.