Subnormothermic Ex vivo lung perfusion temperature improves graft preservation in lung transplantation

Abstract

Background Normothermic machine perfusion is clinically used to assess the quality of marginal donor lungs. Although subnormothermic temperatures have proven beneficial for other solid organ transplants, subnormothermia-related benefits of ex vivo lung perfusion (EVLP) still need to be investigated. Material and Methods: In a rat model, we evaluated the effects of 28◦C temperature on 4-h EVLPs with subsequent left lung transplantation. The recipients were observed for 2 h postoperatively. Lung physiology data were recorded and metabolic parameters were assessed. Results: During the 4-h subnormothermic EVLP, the lung oxygenation was significantly higher (p < 0.001), pulmonary vascular resistance (PVR) lower and dynamic compliance (Cdyn) higher when compared to the 37◦C EVLP. During an end-of-EVLP stress test, we recorded significantly higher flow (p < 0.05), lower PVR (p < 0.05) and higher Cdyn (p < 0.01) in the 28◦C group when compared to the 37◦C group. After the left lung transplantation, Cdyn and oxygenation improved in the 28◦C group, which were comparable to the 37◦C group. Chemokines RANTES, MIP-3α, MIP-1α MCP-1 GRO/KC and pro-inflammatory mediators GM-CSF, G-CSF and TNFα were significantly lower after the 28◦C EVLP and remained low in the plasma of the recipient rats after transplantation. The lungs of the 28◦C group showed significantly lowered myeloperoxidase activity and lowered levels of TNFα and IL-1β. Conclusions: Compared to the normothermic perfusion, the 28◦C EVLP improved Cdyn and PVR and reduced both the release of pro-inflammatory cytokines and myeloperoxidase activity in lung tissue. These observations were also observed after the left lung transplantation in the subnormothermic group. The 28◦C EVLP significantly improved biochemical, physiological and inflammatory parameters in lung donors.