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Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine

BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of smal...

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Autores principales: Hamed, M O, Barlow, A D, Dolezalova, N, Khosla, S, Sagar, A, Gribble, F M, Davies, S, Murphy, M P, Hosgood, S A, Nicholson, M L, Saeb-Parsy, K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038264/
https://www.ncbi.nlm.nih.gov/pubmed/33839750
http://dx.doi.org/10.1093/bjsopen/zrab009
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author Hamed, M O
Barlow, A D
Dolezalova, N
Khosla, S
Sagar, A
Gribble, F M
Davies, S
Murphy, M P
Hosgood, S A
Nicholson, M L
Saeb-Parsy, K
author_facet Hamed, M O
Barlow, A D
Dolezalova, N
Khosla, S
Sagar, A
Gribble, F M
Davies, S
Murphy, M P
Hosgood, S A
Nicholson, M L
Saeb-Parsy, K
author_sort Hamed, M O
collection PubMed
description BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5–3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer’s solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5–3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.
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spelling pubmed-80382642021-04-14 Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine Hamed, M O Barlow, A D Dolezalova, N Khosla, S Sagar, A Gribble, F M Davies, S Murphy, M P Hosgood, S A Nicholson, M L Saeb-Parsy, K BJS Open Original Article BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5–3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer’s solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5–3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions. Oxford University Press 2021-04-11 /pmc/articles/PMC8038264/ /pubmed/33839750 http://dx.doi.org/10.1093/bjsopen/zrab009 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Hamed, M O
Barlow, A D
Dolezalova, N
Khosla, S
Sagar, A
Gribble, F M
Davies, S
Murphy, M P
Hosgood, S A
Nicholson, M L
Saeb-Parsy, K
Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
title Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
title_full Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
title_fullStr Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
title_full_unstemmed Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
title_short Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
title_sort ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038264/
https://www.ncbi.nlm.nih.gov/pubmed/33839750
http://dx.doi.org/10.1093/bjsopen/zrab009
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