Abstract
The quality of marginal donor lungs is clinically assessed with normothermic machine perfusion. Although subnormothermic temperature and perfluorocarbon-based oxygen carriers (PFCOC) have proven favourable for other organ transplants, their beneficial use for ex vivo lung perfusion (EVLP) still requires further investigation. In a rat model, we evaluated on a 4 h EVLP time the effects of PFCOC with either 28 °C or 37 °C perfusion temperatures. During EVLP at 28 °C with PFCOC, we recorded significantly lower lung pulmonary vascular resistance (PVR), higher dynamic compliance (Cdyn), significantly lower potassium and lactate levels, higher lung tissue ATP content, and significantly lower myeloperoxidase tissue activity when compared to the 37 °C EVLP with PFCOC. In the subnormothermic EVLP with or without PFCOC, the pro-inflammatory mediator TNFα, the cytokines IL-6 and IL-7, the chemokines MIP-3α, MIP-1α, MCP-1, GRO/KC as well as GM-CSF, G-CSF and the anti-inflammatory cytokines IL-4 and IL-10 were significantly lower. The 28 °C EVLP improved both Cdyn and PVR and decreased pro-inflammatory cytokines and pCO2 levels compared to the 37 °C EVLP. In addition, the 28 °C EVLP with PFCOC produced a significantly lower level of myeloperoxidase activity in lung tissue. Subnormothermic EVLP with PFCOC significantly improves lung donor physiology and ameliorates lung tissue biochemical and inflammatory parameters.
Highlights
To date, lung transplantation is an accepted modality of care for patients with endstage lung diseases
Current lung machine perfusion assessment before transplantation are performed at normothermia but subnormothermic perfusion evaluation are already in standard clinical use for several solid organs [9,14,27,28,29,30]
We demonstrated with a lung transplantation large animal model the benefits of using perfluorocarbon-based oxygen carriers (PFCOC) with normothermic ex vivo lung perfusion (EVLP) [22]
Summary
Lung transplantation is an accepted modality of care for patients with endstage lung diseases. The preservation of the transplantable and highly metabolic abdominal grafts, the liver and the kidneys, has been improved by mimicking physiological conditions and allowing the continuous elimination of toxic products from the cellular medium while carrying out an active restoration of ATP reserves and glycogen [7,8]. The use before transplantation of hypothermic oxygenated machine perfusion has been reported to preserve kidneys and livers with better results than cold static storage [13]. We document the cytoprotective benefits of reduced cellular metabolism and the protective effect against pro-inflammatory tissue mediators with the use of subnormothermic lung perfusion and PFCOC as a non-inferior setting in comparison to the clinically approved normothermic lung perfusion
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