Subnormothermic Ex Vivo Lung Perfusion Temperature Improves Graft Preservation in Lung Transplantation

Cells. 2021 Mar 29;10(4):748. doi: 10.3390/cells10040748.

Abstract

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.

Keywords: ex vivo lung perfusion; lung transplantation; subnormothermic perfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Chemokines / blood
  • Lung / cytology
  • Lung / physiology*
  • Lung Transplantation*
  • Male
  • Oxygen / metabolism
  • Perfusion*
  • Peroxidase / metabolism
  • Protein Carbonylation
  • Rats
  • Rats, Sprague-Dawley
  • Temperature*
  • Vascular Resistance

Substances

  • Chemokines
  • Adenosine Triphosphate
  • Peroxidase
  • Oxygen