The Effects of Hydrogen Gas Inhalation On Non-Heart-Beating Donor Lung During Ex Vivo Lung Perfusion.

Abstract

Purpose: The shortage of donor lung is a limiting factor in lung transplantation (LTx). In order to resolve this problem, non-heart-beating donor (NHBD) lungs are evaluated in ex vivo lung perfusion (EVLP) system prior to LTx. In this study, the effects of hydrogen gas inhalation on NHBD lungs were investigated during EVLP. Methods: Ten 40kg female pigs were randomly divided into control (n=5) and study group (n=5). After cardiac arrest and one hour of warm ischemic injury, the lungs were harvested after flushing with Perfadex solution, and the lungs assessed in the EVLP system for 4 hours. Steen solution was used as perfusate. During EVLP, the lungs were ventilated in the control group with room air (0.2 of FiO2), and with 2% hydrogen gas in the study group. Oxygen capacity, pulmonary vascular resistance and peak airway pressure were measured every hour for 4 hours during EVLP. After the EVLP, lung specimens were excised for measurement of p38, JNK, and ERK 1/2 phosphorylation, and the expression of IL-1ß, IL-6, IL-8, and TNF-α. Pathologic evaluation was performed using lung injury severity score after H & E stain, and wet/dry ratio was examined. Results: Oxygen capacity in the study group was higher than the control group but did not show a significant difference (p = 0.0862). However, pulmonary vascular resistance (p = 0.0111) and peak airway pressure (p = 0.0189) were significantly lower in the study group. The extents of phosphorylation of p38, JNK, and ERK 1/2 were lower in the study group, but did not show statistically significant difference. The expression of IL-1ß (p = 0.0317), IL-6 (p = 0.0159), IL-8 (p = 0.0195), and TNF-α (p = 0.0159) were all significantly lower in the study group. Lung injury score (p = 0.0358) and wet/dry ratio (p = 0.040) were also lower in the study group.Conclusion: Inhalation of hydrogen gas in NHBD lungs during EVLP may improve the function of damaged lungs, and might possibly increase the utilization of NHBD lungs.