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Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion

Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior...

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Autores principales: Abraham, Nader, Ludwig, Elsa K., Schaaf, Cecilia R., Veerasammy, Brittany, Stewart, Amy S., McKinney, Caroline, Freund, John, Brassil, John, Samy, Kannan P., Gao, Qimeng, Kahan, Riley, Niedzwiecki, Donna, Cardona, Diana M., Garman, Katherine S., Barbas, Andrew S., Sudan, Debra L., Gonzalez, Liara M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592306/
https://www.ncbi.nlm.nih.gov/pubmed/36299444
http://dx.doi.org/10.1097/TXD.0000000000001390
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author Abraham, Nader
Ludwig, Elsa K.
Schaaf, Cecilia R.
Veerasammy, Brittany
Stewart, Amy S.
McKinney, Caroline
Freund, John
Brassil, John
Samy, Kannan P.
Gao, Qimeng
Kahan, Riley
Niedzwiecki, Donna
Cardona, Diana M.
Garman, Katherine S.
Barbas, Andrew S.
Sudan, Debra L.
Gonzalez, Liara M.
author_facet Abraham, Nader
Ludwig, Elsa K.
Schaaf, Cecilia R.
Veerasammy, Brittany
Stewart, Amy S.
McKinney, Caroline
Freund, John
Brassil, John
Samy, Kannan P.
Gao, Qimeng
Kahan, Riley
Niedzwiecki, Donna
Cardona, Diana M.
Garman, Katherine S.
Barbas, Andrew S.
Sudan, Debra L.
Gonzalez, Liara M.
author_sort Abraham, Nader
collection PubMed
description Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model. METHODS. Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice. RESULTS. In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function. CONCLUSIONS. This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model.
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spelling pubmed-95923062022-10-25 Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion Abraham, Nader Ludwig, Elsa K. Schaaf, Cecilia R. Veerasammy, Brittany Stewart, Amy S. McKinney, Caroline Freund, John Brassil, John Samy, Kannan P. Gao, Qimeng Kahan, Riley Niedzwiecki, Donna Cardona, Diana M. Garman, Katherine S. Barbas, Andrew S. Sudan, Debra L. Gonzalez, Liara M. Transplant Direct Intestinal Transplantation Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver. We hypothesized that machine perfusion preservation of intestinal allografts could be achieved and allow for transplantation in a porcine model. METHODS. Using a translational porcine model, we developed a device for intestinal perfusion. Intestinal samples were collected at the time of organ procurement, and after 6 h of machine perfusion for gross and histologic evaluation, hourly chemistry panels were performed on the perfusate and were used for protocol optimization. Following transplantation, porcine recipient physical activity, systemic blood parameters, and vital signs were monitored for 2 d before sacrifice. RESULTS. In initial protocol development (generation 1, n = 8 grafts), multiple metabolic, electrolyte, and acid-base derangements were measured. These factors coincided with graft and mesenteric edema and luminal hemorrhage and were addressed with the addition of dialysis. In the subsequent protocol (generation 2, n = 9 grafts), differential jejunum and ileum perfusion were observed resulting in gross evidence of ileal ischemia. Modifications in vasodilating medications enhanced ileal perfusion (generation 3, n = 4 grafts). We report successful transplantation of 2 porcine intestinal allografts after machine perfusion with postoperative clinical and gross evidence of normal gut function. CONCLUSIONS. This study reports development and optimization of machine perfusion preservation of small intestine and successful transplantation of intestinal allografts in a porcine model. Lippincott Williams & Wilkins 2022-10-24 /pmc/articles/PMC9592306/ /pubmed/36299444 http://dx.doi.org/10.1097/TXD.0000000000001390 Text en Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Intestinal Transplantation
Abraham, Nader
Ludwig, Elsa K.
Schaaf, Cecilia R.
Veerasammy, Brittany
Stewart, Amy S.
McKinney, Caroline
Freund, John
Brassil, John
Samy, Kannan P.
Gao, Qimeng
Kahan, Riley
Niedzwiecki, Donna
Cardona, Diana M.
Garman, Katherine S.
Barbas, Andrew S.
Sudan, Debra L.
Gonzalez, Liara M.
Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
title Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
title_full Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
title_fullStr Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
title_full_unstemmed Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
title_short Orthotopic Transplantation of the Full-length Porcine Intestine After Normothermic Machine Perfusion
title_sort orthotopic transplantation of the full-length porcine intestine after normothermic machine perfusion
topic Intestinal Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592306/
https://www.ncbi.nlm.nih.gov/pubmed/36299444
http://dx.doi.org/10.1097/TXD.0000000000001390
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