Novel Neonatal Piglet Models of Surgical Short Bowel Syndrome With Intestinal Failure

Turner, Justine; Wales, Paul W.; Nation, Patrick N.; Wizzard, Pamela; Pendlebury, Christine; Sergi, Consolato; Ball, Ron O; Pencharz, Paul B.

doi:10.1097/mpg.0b013e3181f18ca0

Cited by 54 publications

(140 citation statements)

References 30 publications

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“…All piglets were aged 5.0 ± 1.0 d at the time they underwent general anesthesia for insertion of a jugular venous catheter and laparotomy for insertion of a gastrostomy feeding tube and intestinal measurement, as previously described (19). Piglets were randomly allocated into three groups: proximal intestinal resection group (n = 16), distal intestinal resection group (n = 17), and sham group (n = 15).…”

Section: Animals and Surgerymentioning

confidence: 99%

“…acid blockade were given per protocol (19). Piglets were maintained for 14 d before terminal laparotomy.…”

Section: Animals and Surgerymentioning

confidence: 99%

“…We previously developed neonatal piglet SBS models with and without ileal resection (19). Neonatal piglets have gastrointestinal anatomy, physiology, and metabolism similar to those of human neonates (20,21).…”

mentioning

confidence: 99%

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Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

et al. 2013

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Background: Short-bowel syndrome (SBS) is the most common cause of neonatal intestinal failure. Recovery requires intestinal adaptation, dependent on enteral nutrition (EN) and growth factors such as glucagon-like peptide-2 (GLP-2), which is secreted from L cells in the ileum. Neonatal SBS often results in loss of ileum; therefore, we hypothesized that without ileum, endogenous GLP-2 production would be inadequate to promote adaptation. We compared endogenous GLP-2 production and adaptation in neonatal animals with SBS, with and without ileum. Methods: Neonatal piglets (4-6 d) were randomized to 75% mid-intestinal resection, 75% distal-intestinal resection, or sham control without resection. Postoperatively, all piglets commenced parenteral nutrition (PN), tapering as EN was increased to maintain specific growth. results: The resected SBS piglets developed intestinal failure, requiring a longer duration of PN support and experiencing fat malabsorption. The piglets without ileum were not able to wean from PN during the study and did not show adaptation, specifically growth in intestinal length or crypt hyperplasia on histology of the jejunum. Adaptation was observed in the resected SBS piglets with ileum, and these piglets also had an increased plasma GLP-2 level that was not observed in piglets without ileum. conclusion: SBS piglets with ileum undergo adaptation associated with increased endogenous GLP-2 production. SBS piglets without ileum undergo limited adaptation and severe intestinal failure, requiring prolonged PN support. This appears to be related to a deficiency in endogenous GLP-2 production. n eonatal intestinal failure secondary to short-bowel syndrome (SBS) has a particularly poor outcome. It is most common in preterm infants, and necrotizing enterocolitis is the most common cause (1-3). Necrotizing enterocolitis usually results in loss of ileum and right colon and carries a significant mortality (4).After intestinal resection, adaptation of the remnant intestine is essential for survival, compensating for the reduced absorptive surface area, both structurally and functionally (5). This process is regulated by several factors, including the stage of intestinal development, site and length of resection, the underlying disease, nutritional status, and gut-derived hormones and growth factors (6). Among the growth factors, glucagon-like peptide-2 (GLP-2) is considered to have an important role in inducing small-intestinal adaptation after resection. GLP-2 acts specifically at the GLP-2 receptor (GLP-2R), which is expressed throughout the small and large intestines but with greatest concentration in the jejunum (7). GLP-2 is uniquely trophic for the intestine (8). It can stimulate residual small-intestinal adaptation by increasing crypt cell proliferation and inhibiting apoptosis, thereby increasing villus height, crypt depth, mucosal mass, and overall small-intestinal length and weight (9-11). Functionally, GLP-2 increases activities of mucosal enzymes and therefore increases digestion and absorption (...

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Section: Animals and Surgerymentioning

confidence: 99%

“…acid blockade were given per protocol (19). Piglets were maintained for 14 d before terminal laparotomy.…”

Section: Animals and Surgerymentioning

confidence: 99%

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Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

et al. 2013

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“…SBS models were seldom described in other types of pig [7,23]. Male animals were used rarely [31,34,35]. …”

Section: Resultsmentioning

confidence: 99%

“…Regarding the exact breed, mostly landrace [10,21,22,30,31] or landrace × large white [5,13,16,20,24,26,32,33,34] animals were used. SBS models were seldom described in other types of pig [7,23].…”

Section: Resultsmentioning

confidence: 99%

Models of Short Bowel Syndrome in Pigs: A Technical Review

Weih

Nickkholgh²,

Keßler³

et al. 2013

Eur Surg Res

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Background: Short bowel syndrome (SBS) is still a life-threatening disease in both children and adults. Although the therapeutic options are improving, challenges still remain, and to overcome these challenges is a major focus of SBS research today. In order to simulate anatomical and physiological conditions similar to those in humans for research, porcine models of SBS are often used. Various approaches for generating SBS models have been described in the literature. Methods/Results: In this work, we present a review of different types of porcine models of SBS and outline the differences between those models regarding types of animals, surgical procedures, monitoring, and methods of assessment. Conclusion: The aim of this study was to select the most suitable SBS model regarding the purpose of the research.

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Novel Long‐Acting GLP‐2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum

Slim

Lansing

Wizzard

et al. 2019

J Parenter Enteral Nutr

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BackgroundGlucagon‐like peptide‐2 (GLP‐2) is an intestinotrophic factor released from L‐cells in the ileum, a segment commonly resected or atretic in neonatal short bowel syndrome (SBS). In piglets, ileal resection decreases intestinal adaptation and endogenous GLP‐2 production, whereas exogenous replacement promotes adaptation. In this study, we determined the effect of a novel long‐acting GLP‐2 analogue, FE 203799 (FE; apraglutide), upon intestinal growth, adaptation, and function in neonatal SBS piglets without ileum.MethodsNeonatal piglets were randomized to saline (n = 10) vs FE treatment (n = 8). All piglets underwent 75% intestinal resection with jejunocolic anastomosis and were pair‐fed parenteral and enteral nutrition. Saline and FE (5 mg/kg) treatments were administered subcutaneously on days 0 and 4. On day 6, 24‐hour fecal samples were collected for subsequent nutrient analysis. On day 7, small‐intestinal length and weight were measured and tissue collected for analyses.ResultsOn day 7, saline and FE‐treated piglets were healthy and gained equivalent weight (P = 0.12). Compared with saline piglets, FE‐treated piglets had lower fecal fat (P = 0.043) and energy (P = 0.043) losses and exhibited intestinal lengthening (P = 0.001), greater small‐intestinal weight (P = 0.004), longer villus height (P = 0.027), and greater crypt depth (P = 0.054).ConclusionsThe subcutaneous GLP‐2 analogue, FE, enhanced intestinal adaptation in a neonatal model of SBS without ileum. The observed intestinal lengthening with FE treatment was unique compared with our prior experience with native GLP‐2 in this same model and has important clinical implications for treating neonatal SBS. At this developmental stage, growth in the intestine, if augmented, could accelerate weaning from parenteral nutrition.

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Novel Neonatal Piglet Models of Surgical Short Bowel Syndrome With Intestinal Failure

Cited by 54 publications

References 30 publications

Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

Role of glucagon-like peptide–2 deficiency in neonatal short-bowel syndrome using neonatal piglets

Models of Short Bowel Syndrome in Pigs: A Technical Review

Novel Long‐Acting GLP‐2 Analogue, FE 203799 (Apraglutide), Enhances Adaptation and Linear Intestinal Growth in a Neonatal Piglet Model of Short Bowel Syndrome with Total Resection of the Ileum

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