An iterative design approach to development of an ex-vivo normothermic multivisceral perfusion platform

Abstract

Challenges in normothermic machine perfusion (NMP) remain, particularly concerning the duration for which individual organs can be safely preserved. We hypothesize that optimal preservation can be achieved by perfusing organs together in a multivisceral block. Therefore, our aim was to establish a platform for ex vivo multivisceral organ perfusion. Multivisceral grafts containing the liver, kidneys, pancreas, spleen and intestine were obtained from Yorkshire pigs. Three generation (gen) setups were tested during the iterative design process, and minor changes were made throughout. Gen1 (n=4) used a custom-designed single perfusion circuit. Gen2 (n=3) employed a dual perfusion circuit. Gen3 (n=4) featured a single perfusion circuit with an optimized basin and reservoir. Grafts underwent NMP using an autologous blood-based perfusate, while hemostatic parameters and function were assessed. With each iteration, aortic flow improved, resistance decreased, urine output increased, oxygen consumption rose, perfusate lactate levels dropped, and pH stability improved. Cellular injury trended lower in Gen3. Histological evaluation demonstrated minimal differences in Gen2 and 3. We demonstrate the feasibility of abdominal multivisceral NMP for up to 8 hours. Adequate arterial flow, stable perfusate pH, and high oxygen consumption in setup 3 indicate organ viability. Multivisceral perfusion may serve as a platform for long-term NMP.