TY - JOUR
T1 - An Iterative Design Approach to Development of an Ex Situ Normothermic Multivisceral Perfusion Platform
AU - van Leeuwen, L. Leonie
AU - Holzner, Matthew L.
AU - McKenney, Ceilidh
AU - Todd, Rachel
AU - Frost, Jamie K.
AU - Gudibendi, Sneha
AU - Kim-Schluger, Leona
AU - Schiano, Thomas
AU - Florman, Sander
AU - Akhtar, M. Zeeshan
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/7
Y1 - 2025/7
N2 - Background/Objectives: 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 situ multivisceral organ perfusion. Methods: Multivisceral grafts containing the liver, kidneys, pancreas, spleen, and intestine were obtained from Yorkshire pigs. Three generation (gen) set-ups were tested during the iterative design process, and minor changes were made throughout. Gen 1 (n = 4) used a custom-designed single perfusion circuit. Gen 2 (n = 3) employed a dual perfusion circuit. Gen 3 (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. Results: Comparing Gen 1 versus Gen 3, the mean aortic flow improved (1.018 vs. 2.089 L), resistance decreased (0.224 vs. 0.038), urine output increased (51.90 vs. 271.3 mL), oxygen consumption rose (43.56 vs. 49.52 mL O2/min), perfusate lactate levels dropped (10.44 vs. 3.10 mmol/L), and the pH became more physiological (7.27 vs. 7.30). Cellular injury trended lower in Gen 3. Histological evaluation demonstrated minimal differences in Gens 2 and 3. Conclusions: We demonstrate the feasibility of abdominal multivisceral NMP for up to 8 h. Adequate arterial flow, stable perfusate pH, and high oxygen consumption in setup 3 indicated organ viability. Multivisceral perfusion may serve as a plat-form for long-term NMP.
AB - Background/Objectives: 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 situ multivisceral organ perfusion. Methods: Multivisceral grafts containing the liver, kidneys, pancreas, spleen, and intestine were obtained from Yorkshire pigs. Three generation (gen) set-ups were tested during the iterative design process, and minor changes were made throughout. Gen 1 (n = 4) used a custom-designed single perfusion circuit. Gen 2 (n = 3) employed a dual perfusion circuit. Gen 3 (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. Results: Comparing Gen 1 versus Gen 3, the mean aortic flow improved (1.018 vs. 2.089 L), resistance decreased (0.224 vs. 0.038), urine output increased (51.90 vs. 271.3 mL), oxygen consumption rose (43.56 vs. 49.52 mL O2/min), perfusate lactate levels dropped (10.44 vs. 3.10 mmol/L), and the pH became more physiological (7.27 vs. 7.30). Cellular injury trended lower in Gen 3. Histological evaluation demonstrated minimal differences in Gens 2 and 3. Conclusions: We demonstrate the feasibility of abdominal multivisceral NMP for up to 8 h. Adequate arterial flow, stable perfusate pH, and high oxygen consumption in setup 3 indicated organ viability. Multivisceral perfusion may serve as a plat-form for long-term NMP.
KW - machine perfusion
KW - multivisceral transplantation
KW - organ preservation
UR - https://www.scopus.com/pages/publications/105010281876
U2 - 10.3390/jcm14134620
DO - 10.3390/jcm14134620
M3 - Article
AN - SCOPUS:105010281876
SN - 2077-0383
VL - 14
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 13
M1 - 4620
ER -