Optimal temperature for Ex Vivo Lung Perfusion (EVLP): 25 C or 30 C?

Two recent studies in rats suggest that temperatures of 25 C - 30 C may be optimal for EVLP.

Ex-vivo lung perfusion is normally performed at normothermia (37 C) but sub-normothermic machine perfusion settings at 25-30 C(1,2) or even lower(3) are already in clinical use for other solid organ transplants, particularly for liver. Hypothermia below 25 C however may not be applicable to the lung because ventilating at hypothermia may cause structural damage.

A couple of recent studies from Zurich(4) and Duke, USA(5), now suggest that sub-normothermia (25 C – 30 C) may be optimal for ex-vivo perfusion of lungs too. Both studies however were performed on rat lungs subjected to four hours of EVLP.

The Zurich(4) study evaluated the effects of four-hour EVLP at 28 C and at 37 C with subsequent left lung transplantation and two hours of post-transplant observation. Oxygenation was significantly higher (p < 0.001), pulmonary vascular resistance (PVR) lower and dynamic compliance (Cdyn) higher at 28 C when compared to EVLP at 37 C.

In addition, EVLP at 28 C reduced the release of pro-inflammatory cytokines and lowered myeloperoxidase activity in lung tissue, with both trends continuing after transplantation. Other clinical chemistry data for potassium, anion gap K+ but also lactate and glucose levels in the EVLP perfusate or in the plasma of transplanted animals indicated a beneficial effect of the EVLP performed at 28 C compared to the 37 C group. In short, EVLP at 28 C significantly improved biochemical, physiological and inflammatory parameters in lung donors.

Similar findings were reported from Duke(5), where the effects of four hours of EVLP on rat lungs were assessed at three different temperatures, 37 C, 30 C and 25 C and compared with a static cold preservation group as control. Here again, observations continued for two hours after transplantation of the left lung.

Although there were no evident differences between temperature groups in terms of oxygen extraction (Pao2/FiO2 ratio), there was a significant increase in the production of inflammatory mediators (TNF-a, etc) during EVLP at 37 C, but not at lower temperatures. On histologic grading after transplantation, greater injury was observed in the 30 C and 37 C groups, but not 25 C, when compared with static cold storage.

Given that the donor lung comes with an inflammatory load and that EVLP itself may generate an inflammatory load, reducing temperature may benefit, with reduced tissue injury, both situations. Alternatively, we can regard EVLP as the first stage of reperfusion. Mild hypothermia may be an adjunct to the other aspects of EVLP – such as controlled pressure and flow, absence of recipient neutrophils, very high concentration of steroids – all of which may reduce reperfusion injury.

XVIVO Insights PB-2021-04-20


1. P Fontes, et al: Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under sub-normothermic conditions. Am J Transplant . 2015 Feb;15(2):381-94. doi: 10.1111/ajt.12991. PMID: 25612645
2. Knaak, J.M, et al: Technique of sub-normothermic ex vivo liver perfusion for the storage, assessment, and repair of marginal liver grafts. J. Vis. Exp. 2014, e51419.
3. Van Rijn R, et al: Hypothermic Machine Perfusion in Liver Transplantation – A Randomized Trial. N Engl J Med 2021 Apr 15;384(15):1391-1401. doi: 10.1056/NEJMoa2031532. Epub 2021 Feb 24.
4. Stephan Arni , et al: Sub-normothermic Ex Vivo Lung Perfusion Temperature Improves Graft Preservation in Lung Transplantation. Cells 2021 Mar 29;10(4):748.  doi: 10.3390/cells10040748 (link to Abstract)
5. Gloria JN, et al: Sub-normothermic ex vivo lung perfusion attenuates graft inflammation in a rat transplant model. Duke Ex Vivo Organ Laboratory. J Thorac Cardiovasc Surg. 2021 Jan 30:S0022-5223(21)00165-3. doi: 10.1016/j.jtcvs.2021.01.066  PMID: 33640121 (link to Abstract)