Hypothermic machine perfusion improves the quality of marginal donor pancreata
Marjolein Leemkuil1, Marten M.A. Engelse2, Rutger R.J. Ploeg3, Eelco E.J.P. de Koning2, Christina C. Krikke1, Henri H.G.D. Leuvenink1.
1Department of surgery, University Medical Center Groningen, Groningen, Netherlands; 2Department of nephrology, Leids Universitair Medisch Centrum, Leiden, Netherlands; 3Department of transplantation, Oxford Transplant Center, Oxford, United Kingdom
Introduction: Pancreas or islet transplantation is considered the most effective treatment for patients with type 1 diabetes mellitus. Due to the persistent organ shortage, pancreata from marginal donors are more frequently used for transplantation or islet isolation. These grafts are more vulnerable to ischemic damage. The traditional preservation method, cold storage (CS), might not be sufficient to completely prevent this damage. In kidneys and livers, hypothermic machine perfusion (HMP) is shown to be superior to CS, especially for the more marginal donor organs. The aim of this project was to study the potential beneficial effect of HMP on the pancreas.
Methods: 8 human pancreata (4 from Donation after Circulatory Death (DCD) donors and 4 from Donation after Brain Death (DBD) donors) were preserved by HMP and 8 (divided in two similar groups) by CS. HMP was performed for 6 hours with oxygenated Belzer Machine Perfusion Solution® with a dual perfusion system to allow perfusion via the mesenteric superior artery and the splenic artery separately. The perfusion pressure was set to 25 mmHg. Tissue biopsies and samples of the preservation fluid were collected at baseline and after 6 hours of preservation for histology, tissue ATP measurement and enzyme level analysis. In addition, pancreas weight was measured before and after preservation as a measurement of edema formation.
Results: No significant difference in pancreas weight increase was seen after preservation by CS or HMP. Histological analysis of the tissue showed an intact structure of the pancreatic tissue after HMP. During HMP, amylase, lipase and LDH levels in the preservation fluid increased reaching a plateau after 4 hours. No increase was found in enzyme levels after CS. At baseline, adenosine triphosphate (ATP) content in the DCD group (8,2 +- 5,6 µmol/gram protein) was significantly lower than in the DBD group (43,5 +- 16,2 µmol/gram protein). During CS, ATP content decreased in both groups. In contrast, in the HMP preserved pancreata, ATP content increased to 47,9 +- 25 (DCD) and 136,4 +- 144 (DBD) µmol/gram protein. In the DCD group, the ATP content after HMP was significant higher compared to CS and it was equivalent to the ATP content at baseline in the DBD group.
Conclusion: HMP improves the viability of donor pancreata, demonstrated by increased ATP levels. In addition, we postulate that pancreas quality is enhanced by washout of degrading enzymes. The viability of marginal pancreata, such as DCD pancreata, could reach that of DBD pancreata using HMP. Enlargement of the pancreas donor pool is therefore likely.
15:30 - 17:00
|Pancreas & Islet Donors: Assessing Risk and Optimizing Outcomes||Hypothermic machine perfusion improves the quality of marginal donor pancreata.||Room 110|