Ex Vivo Normothermic Perfusion of Isolated Segmental Porcine Bowel: A Novel Functional Model of the Small Intestine.
1University Department of Surgery, Cambridge NIHR Biomedical Research Centre and NIHR Blood and Transplant Research Unit in Organ Donation and Transplantation, Cambridge, Cambridgeshire, United Kingdom
2Wellcome Trust &ndash
MRC Institute of Metabolic Science, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom
3MRC Mitochondrial Biology Unit, Cambridge, Cambridgeshire, United Kingdom
Meeting: 2017 American Transplant Congress
Abstract number: 462
Keywords: Graft function, Intestinal transplantation
Session Information
Date: Tuesday, May 2, 2017
Session Name: Concurrent Session: Small Bowel: All Topics
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: E271b
Introduction: There is a need for the development of suitable large animal models for research in gastroenterology and intestinal transplantation. Ex vivo normothermic perfusion (EVNP) is increasingly used for studying isolated organs under controlled perfusion conditions. Here we report, for the first time, a reliable and effective technique for EVNP of segmental porcine small intestine.
Methods: Segments of small intestine (n=4) 1.5-3.0m were retrieved from terminally-anaesthetised pigs following exsanguination and in situ perfusion with cold preservation solution. EVNP was performed after a mean cold ischaemia time of 5h 20min using oxygenated autologous blood diluted with Ringer's solution. EVNP was performed at 37[deg]C with a mean pressure of 80 mmHg for 2h. The duration of EVNP was extended to 4h for the second experiments in which two segments of proximal to mid-ileum (1.5-3.0m) were retrieved from each pig (n=5) and reperfused with whole blood (control) or with leukocyte-depleted blood to examine the impact of leukocyte depletion on reperfusion injury.
Results: All bowel segments were well-perfused, exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (basal level 1.8±0.6 mmol/L vs. peak 15.5±5.8 mmol/L) and glucagon-like peptide-1 (GLP-1) levels also increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between the control group (n=5) and the leukocyte-depleted group (n=5) in blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4h of EVNP.
Conclusion: We provide proof-of-concept evidence for the utility of this novel experimental model for the investigation of intestinal physiology, pathology and ischaemia reperfusion injury, as well as for evaluation of potential therapeutic interventions.
CITATION INFORMATION: Hamed M, Barlow A, Khosla S, Sagar A, Gribble F, Murphy M, Pettigrew G, Bolton E, Bradley J, Nicholson M, Hosgood S, Saeb-Parsy K. Ex Vivo Normothermic Perfusion of Isolated Segmental Porcine Bowel: A Novel Functional Model of the Small Intestine. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Hamed M, Barlow A, Khosla S, Sagar A, Gribble F, Murphy M, Pettigrew G, Bolton E, Bradley J, Nicholson M, Hosgood S, Saeb-Parsy K. Ex Vivo Normothermic Perfusion of Isolated Segmental Porcine Bowel: A Novel Functional Model of the Small Intestine. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/ex-vivo-normothermic-perfusion-of-isolated-segmental-porcine-bowel-a-novel-functional-model-of-the-small-intestine/. Accessed April 18, 2019.« Back to 2017 American Transplant Congress