Sub-normothermic Ex Vivo Lung Perfusion Temperature Improves Graft Preservation in Lung Transplantation

Stephan Arni, Tatsuo Maeyashiki, Necati Citak, Isabelle Opitz, Ilhan Inci (Zurich)  Cells 2021 Mar 29;10(4):748.  doi: 10.3390/cells10040748.PMID: 33805274  DOI: Full text at : https://www.mdpi.com/2073-4409/10/4/748/htm#B30-cells-10-00748

Normothermic machine perfusion is clinically used to assess the quality of marginal donor lungs. Although sub-normothermic temperatures have proven beneficial for other solid organ transplants, sub-normothermia-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 sub normothermic 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.