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

Author:

Abraham Nader1,Ludwig Elsa K.2,Schaaf Cecilia R.2,Veerasammy Brittany2,Stewart Amy S.2,McKinney Caroline2,Freund John2,Brassil John3,Samy Kannan P.1,Gao Qimeng1,Kahan Riley1,Niedzwiecki Donna4,Cardona Diana M.5,Garman Katherine S.1,Barbas Andrew S.1,Sudan Debra L.1,Gonzalez Liara M.2

Affiliation:

1. Duke Ex-Vivo Organ Lab (DEVOL), Division of Abdominal Transplantation, Department of Surgery, Duke University School of Medicine, Duke University, Durham, NC.

2. Intestinal Regenerative Medicine Lab, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.

3. Functional Circulation, LLC, Lake Mills, WI.

4. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Duke University, Durham, NC.

5. Department of Pathology, Duke University Medical Center, Durham, NC.

Abstract

Background. 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Transplantation

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