Normothermic ex situ pancreas perfusion for the preservation of porcine pancreas grafts

Abstract

Pancreas transplantation improves and extends the life of patients with insulin‐dependent diabetes. Pancreata from extended criteria donors have been increasingly used due to the scarcity of available grafts. Normothermic ex situ pancreas perfusion (NESPP) can keep grafts metabolically active, potentially allowing for assessment and organ repair, and could improve outcomes of marginal grafts. A novel NESPP technique was developed and tested. Porcine pancreata were removed after a short period of warm ischemia and subjected to 6 h of NESPP. Perfusion parameters, potential graft assessment markers and graft injury were measured. Next, pancreata subjected to 3 h of NESPP were transplanted and animals were followed for up to 3 days. Graft function and injury post‐transplantation were evaluated. Using this novel system of perfusion, pancreata were perfused for an extended period of time with minimal edema. Histology at the end of perfusion showed intact islet cells with only mild signs of tissue injury. NESPP transplanted grafts showed immediate function after transplantation, with glucose levels in normal range. NESPP maintains a physiologic environment and excellent graft function without causing significant graft injury. Porcine pancreas transplantation is feasible and allows for in vivo graft assessment of pancreas function and injury after NESPP.

Pancreas Ex-Situ Preservation and Evaluation. Development of a Normothermic Machine Perfusion System

“…Some other NP models mention the use of a dialysis membrane in their experiences, something we did not include yet in our design. We agree that it appears essential for prolonged NP with the Toronto group, Mazilescu et al reporting an absence of oedema and ionic imbalance after 6 hours of NP by incorporating this 15 . This group notably reported the addition of aprotinin to their perfusate reduce the inflammatory response and reduce diffuse micro-thromboses 15 .…”

“…We agree that it appears essential for prolonged NP with the Toronto group, Mazilescu et al reporting an absence of oedema and ionic imbalance after 6 hours of NP by incorporating this 15 . This group notably reported the addition of aprotinin to their perfusate reduce the inflammatory response and reduce diffuse micro-thromboses 15 . A dialysis membrane is easily added to our system, we ensured to monitor serial electrolyte levels with an ionogram and correct when required.…”

“…Other pre-clinical studies have cited other perfusate compositions, to limit oedema, some groups have proposed adding different components to the perfusion solution. The addition of gelofusin 13 , albumin 14 or STEEN solution 15 has been proposed. By using autologous whole blood we have maintained normal presumed oncotic pressure for the model.…”

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

“…Amylase and lipase levels don't seem to be reliable markers, since we are using a closed system, and don't seem to correlate with the histopathology 19 . So far, our group has also managed to transplant pancreas allografts after perfusion with good results 17 .…”

“…The venous outflow leads the perfusate back into the venous reservoir. (Adapted from17 ). Please click here to view a larger version of this figure.…”