Hydrogen-Rich Preservation Solution Attenuates Lung Ischemia-Reperfusion Injury after Prolonged Cold Ischemia in a Canine Left Lung Transplant Model

Abstract

Purpose Molecular hydrogen (H2) has been reported as having protective effects on ischemia-reperfusion injury (IRI) in various organs. However, most of the reports are on inhalation of H2. Our group has previously reported the protective effects of H2-rich solution on lung IRI in a rat hilar-clamp model (Takahashi M, et al. Eur J Cardiothorac Surg 2017; 51: 442-448.) and the protective effects of hydrogen-rich preservation solution on lung preservation in a rat left lung transplant (LTx) model (Saito M, et al. J Heart Lung Transplant 2018; 37: S226). In this study, we examined the protective effects of hydrogen-rich preservation solution on lung preservation in a canine left LTx model. Methods TOYO beagles underwent orthotopic left LTx after cold ischemia followed by reperfusion (RP) for 4 hours. Forty-five minutes after RP, the right main pulmonary artery was clamped for evaluating the implanted graft function. Beagles were divided into two groups: control group (CON, n=4) and hydrogen group (H2, n=4). In the CON groups, donor lungs were flushed and immersed for 23 hours cold preservation at 4 °C by the preservation solution (ET-Kyoto Solution). In the H2 groups, donor lungs were flushed and immersed by the hydrogen-rich ET-Kyoto Solution. Arterial blood gas analysis, lung mechanics, and pulmonary vascular resistance (PVR) were evaluated during RP. After RP, wet-to-dry ratio (W/D) was evaluated. Results Compared with the CON group, significantly higher partial pressure of arterial oxygen (Figure A) and significantly lower partial pressure of carbon dioxide in the H2 group was observed 4 hours after RP. Although not statistically significant, dynamic lung compliance was better and PVR was lower in the H2 group than in the CON group (Figure B, C). Furthermore, W/D in the H2 group was significantly lower than that in the CON group (Figure D). Conclusion Our results indicated that hydrogen-rich preservation solution attenuated IRI in a canine left LTx model.