Reperfusion Inflammatory State of Human Lungs during Cellular Ex-Vivo Perfusion

Abstract

Purpose Normothermic cellular ex-vivo lung perfusion (EVLP) can provide a platform for studying ischemia-reperfusion injury (IRI), with the donor lungs being the only source of cytokine appearance in the perfusate. The inflammatory effects of cellular EVLP on lungs are inadequately explored. Herein, we aimed to examine the reperfusion inflammatory state during cellular EVLP in relation to donor factors and impact on lung function. Methods For research purposes, 42 clinically rejected donor lungs underwent normothermic cellular EVLP with open left atrium and flow equivalent to 100% of cardiac output for 2 hours. Reasons for rejection were donor old age, smoking history, low PO2/FiO2 (P/F) ratio, or unavailability of a matched recipient. Perfusate samples were collected at the beginning of EVLP (0 hours), then at 1 and 2 hours of EVLP. Lung weight was measured at the end of EVLP as an indicator for the degree of edema. Data were presented as median (interquartile range). Results Interleukin (IL)-6, IL-8, IL-10, IL-1β, and tumor necrosis factor (TNF)-α were significantly up-regulated in the EVLP perfusate at 1 and 2 hours compared to baseline 0 hours (p Conclusion Cytokine array has shown that cellular EVLP is associated with reperfusion inflammatory state in human lungs. IL-1β and IL-10 were mostly affected by donor factors, while IL-6, IL-8, and TNF-α had the most effect on lung function during EVLP. These results suggest that cellular EVLP can be utilized to study human lung IRI and develop therapeutic targets.