Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation

Objectives: Ischemia/reperfusion injury (IRI) is a common complication of lung transplantation (LTx). Hydrogen sulfide (H₂S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pretreatment with inhaled H₂S would improve graft function in an ex vivo model of LTx. Methods: Rabbits (n = 10) were ventilated for 2 h prior to heart-lung bloc procurement. The treatment group (n = 5) inhaled room air (21% O₂) supplemented with 150 ppm H₂S while the control group (n = 5) inhaled room air alone. Both groups were gradually cooled to 34°C. All heart-lung blocs were then recovered and cold-stored in low-potassium dextran solution for 18 h. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. Results: Prior to heart-lung bloc procurement, rabbits pretreated with H₂S exhibited similar oxygenation (P = 0.1), ventilation (P = 0.7), and heart rate (P = 0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures (P = 0.01). During reperfusion, lungs pretreated with H₂S had better oxygenation (P < 0.01) and ventilation (P = 0.02), as well as lower pulmonary artery pressures (P < 0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion (P = 0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity (P = 0.01). Conclusions: To our knowledge, this study represents the first reported therapeutic use of inhaled H₂S in an experimental model of LTx. After prolonged ischemia, lungs pretreated with inhaled H₂S exhibited improved graft function during reperfusion. Donor pretreatment with inhaled H₂S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration.