Hydrogen Gas Improves Lung Transplant Success in Rats
- Authors
- Kentaro Noda, Norihisa Shigemura, Yugo Tanaka, Jay Bhama, Jonathan D’Cunha, Hirosuke Kobayashi, James D. Luketich, Christian A. Bermudez
- Journal
- Transplantation
- Year
- 2014
- DOI
- 10.1097/TP.0000000000000254
- Study Type
- Rat
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- United States
- Health Condition
- End-Stage Lung Disease
- Body System
- Respiratory
TL;DR
Inhaling hydrogen gas before a lung transplant procedure helps reduce inflammation and improve lung function after the transplant.
Key Finding
Hydrogen gas preconditioning during lung preservation reduced inflammatory responses and metabolic stress while improving the function of transplanted lungs in rats.
Summary
This rat study tested whether adding hydrogen gas to the air used during lung preservation could improve the quality of lungs before transplant. Researchers found that the standard preservation process triggered inflammation and metabolic stress in the lungs, but exposing the lungs to 2% hydrogen gas reduced these harmful effects, improved the lungs' energy production, and resulted in better function after transplant into recipient rats.
Practical Takeaway
This is an early-stage rat study showing hydrogen gas may help preserve donor lungs for transplant, but it has not been tested in humans. The findings are promising for organ transplant medicine, though much more research would be needed before this approach could be used clinically.
Abstract
Background: Although the benefits of ex vivo lung perfusion (EVLP) have been globally advocated, the potentially deleterious effects of applying EVLP, in particular activation of proinflammatory cascades and alteration of metabolic profiles, are rarely discussed. This study examined proinflammatory events and metabolic profiles in lung grafts on EVLP and tested whether preconditioning lung grafts with inhaled hydrogen, a potent, cytoprotective gaseous signaling molecule, would alter the lungs' response to EVLP. Methods: Rat heart-lung blocks were mounted on an acellular normothermic EVLP system for 4 hr and ventilated with air or air supplemented with 2% hydrogen. Arterial and airway pressures were monitored continuously; perfusate was sampled hourly to examine oxygenation. After EVLP, the lung grafts were transplanted orthotopically into syngeneic rats, and lung function was examined. Results: Placing lung grafts on EVLP resulted in significant upregulation of the messenger RNAs for several proinflammatory cytokines, higher glucose consumption, and increased lactate production. Hydrogen administration attenuated proinflammatory changes during EVLP through upregulation of the heme oxygenase-1. Hydrogen administration also promoted mitochondrial biogenesis and significantly decreased lactate production. Additionally, in the hydrogen-treated lungs, the expression of hypoxia-inducible factor-1 was significantly attenuated during EVLP. These effects were maintained throughout EVLP and led to better posttransplant lung graft function in the recipients of hydrogen-treated lungs. Conclusions: Lung grafts on EVLP exhibited prominent proinflammatory changes and compromised metabolic profiles. Preconditioning lung grafts using inhaled hydrogen attenuated these proinflammatory changes, promoted mitochondrial biogenesis in the lungs throughout the procedure, and resulted in better posttransplant graft function.