Strategies to prolong homeostasis of ex vivo perfused lungs.
Takashima M, Cheung H Y A, Watanabe T, Liu M, Keshavjee S, : Extended pig EVLP research group. J Thoracic Cardiovasc Surg, Aug 12 , 2020 (in press) https://doi.org/10.1016/j.jtcvs.2020.07.104
Ex vivo lung perfusion (EVLP) provides an innovative method to assess and repair donor lungs. The current Toronto EVLP protocol can reliably and reproducibly preserve lungs for 12h. A longer EVLP preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24h normothermic EVLP.
We systematically examined three modifications of EVLP perfusate administration in a large animal 24h EVLP model. Pig lungs were assigned to 4 groups (n = 5 per group): 1. control; 2. continuous replacement (CR) of EVLP perfusate; 3. modified feed (MF), which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and 4. total parenteral nutrition (TPN), in which we added parenteral nutrition to the perfusate.
Only 1 lung in the control group completed 24h EVLP. However, 24h perfusion was achieved in 4 lungs in the CR group, 3 lungs in the MF group, and 4 lungs in the TPN group. The TPN group achieved significantly longer stable perfusion time compared to control (p=0.03). Lung function was significantly improved and inflammatory cytokine production was reduced in the CR and TPN groups compared to control.
Modifications of EVLP perfusate towards achieving a stable homeostatic state can extend perfusion time for up to 24h. While these modifications allow for prolonged EVLP, further research will be required to develop stable lung support beyond 24h.