Normothermic <em>Ex Vivo</em> Pancreas Perfusion for the Preservation of Pancreas Allografts before Transplantation

Abstract

Pancreas transplantation (PTx) is a curative treatment for people who live with the burden of a diagnosis of diabetes mellitus (DM). However, due to organ shortages and increasing numbers of patients being listed for PTx, new strategies are needed to increase the number of available grafts for transplantation.Static cold storage (SCS) is considered the gold standard for standard criteria organs.However, standard criteria donors (SCD) are becoming scarce and new strategies that can increase the rate of organ acceptance from extended criteria donors (ECD) are urgently needed.Normothermic ex vivo perfusion (NEVP) is one of the strategies that has become increasingly popular over the past couple of decades. This preservation method has already been used successfully in other organs (liver, kidneys, and lungs) but has been minimally explored in pancreas transplantation. The few papers that describe the method for pancreas show little success, edema being one of the major issues. The following manuscript describes the successful NEVP method and setup developed by our group to perfuse swine pancreas.

Reanimating Pancreatic Grafts Subjected to Prolonged Cold Ischemic Injury Using Normothermic Ex Vivo Perfusion

“…16 Similarly, for dialysate, we used a higher concentration of salt (1.5 versus 1 g/L as previously described) based on lower edema and more physiological perfusion milieu achieved by us in a series of our previous perfusion experiments. 15 At the back-table, all arterial branches were tied off, and the spleen was removed. Next, the aorta was cannulated using a 1/4" × 3/8" cannula (in the NEVP group).…”

“…The anesthetic and surgical procedures in the donor operation were performed according to the step-by-step protocol described in detail previously by our group. 15 A policy of minimal handling of the native pancreas was followed to ensure a minimally inflamed graft at the end of the operation. After systemic administration of heparin (500 IU/kg bodyweight) through the central venous catheter, blood was drained and collected (usually 800-1000 mL) in bags containing Citrate Phosphate Dextrose Saline Adenine Glucose-Mannitol (CPD/ SAG-M), used later as a component in the perfusate used in NEVP.…”

Machine Perfusion of the Pancreas: What Can We Learn from five Decades of Experimental Studies?

“…Animal studies further supported the recent findings with perfusion of human pancreases. Shorter endischemic NMP of 90min to 5hrs resulted in well-maintained tissue and limited inflammation [8,30,31,[49][50][51][52][53][54]. Most studies included DBD pancreas and lack a high risk donor model.…”

“…In-house devices and ECMO-based equipment were used by many. Various perfusate compositions were reported in the literature with autologous whole blood or washed erythrocytes as oxygen carriers in most recent studies [30,31,49]. Particularly in older studies the cold ischemia time before NMP is frequently not reported (Supplementary Table 2) [8,[52][53][54][55].…”

“…With the recent improvement of available perfusion devices, Normothermic Machine Perfusion (NMP) of the pancreas is increasingly explored. The advantage is the opportunity to test viability and to "imitate" the transplant setting as preclinical intervention [7,30,31]. Comparative clinical studies with transplantation after cold or warn machine perfusion are lacking.…”