title: Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation.
abstract: OBJECTIVE
  Ischemia/reperfusion injury (IRI) is a common complication of lung transplantation (LTx). Hydrogen sulfide (H(2)S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pretreatment with inhaled H(2)S 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% O(2)) supplemented with 150 ppm H(2)S 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 H(2)S 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 H(2)S 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 H(2)S in an experimental model of LTx. After prolonged ischemia, lungs pretreated with inhaled H(2)S exhibited improved graft function during reperfusion. Donor pretreatment with inhaled H(2)S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration.
authors: Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors: Timothy J
authors: TJ
authors: George
authors: George J
authors: GJ
authors: Arnaoutakis
authors: Claude A
authors: CA
authors: Beaty
authors: Simran K
authors: SK
authors: Jandu
authors: Lakshmi
authors: L
authors: Santhanam
authors: Dan E
authors: DE
authors: Berkowitz
authors: Ashish S
authors: AS
authors: Shah
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D003576:Electron Transport Complex IV / Q000502:physiology; D006862:Hydrogen Sulfide / Q000008:administration & dosage* / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply; D016040:Lung Transplantation; D008297:Male; D023421:Models, Animal; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control
chemical_list: D017382:Reactive Oxygen Species; D000242:Cyclic AMP; D003576:Electron Transport Complex IV; D006862:Hydrogen Sulfide