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

Background: Pancreas transplantation is currently the best option for patients with severe complications of diabetes. This organ is however particularly vulnerable to Ischemia-Reperfusion-Injury (IRI) and the transplant procedure is associated with a high risk for recipient complications. It is therefore surprising, that testing and routine use of dynamic preservation strategies is lacking behind other solid organs. Methods: This study includes first, a literature review on the evolution of cold and warm pancreas machine perfusion strategies. Second, pressure-controlled hypothermic oxygenated perfusion (HOPE, pO2>60kPa) with fluoresceine is performed in porcine pancreases. Results: No single human pancreas transplant study with machine perfusion is available. A few older animal studies exist with prolonged Hypothermic Machine Perfusion (HMP), with however high perfusion pressures and a lack of active perfusate oxygenation. Tissue oedema and inflammation were the direct consequences. Only recently, such HMP-conditions were adapted, providing an actively oxygenated perfusate at lower perfusion pressures and shorter durations. Such HOPEtreatment was found superior to cold storage and normothermic perfusion in early experimental studies. In our series, HOPE achieved a complete pancreas perfusion, as confirmed by fluorescence despite lower perfusion pressures. Conclusion: HMP with active perfusate oxygenation may achieve similar protective effects in pancreases as seen with livers and kidneys. Lower perfusion pressures appear sufficient to distribute the required oxygen for mitochondrial reprogramming to reduce posttransplant IRI. Prospective clinical studies are planned to test the HOPE-technique in human pancreas transplantation.