Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats.
BACKGROUND
Successful abrogation of ischemia/reperfusion (I/R) injury of lung grafts could significantly improve short- and long-term outcomes for lung transplant (LTx) recipients. Hydrogen gas has potent antioxidant and antiapoptotic properties and has been recently used in number of experimental and clinical studies. The purpose of this research was to investigate whether inhaled hydrogen gas could reduce graft I/R injury during lung transplantation.


METHODS
Orthotopic left LTxs were performed in syngenic Lewis rats. Grafts were perfused with and stored in low potassium dextran solution at 4°C for 6 hr. The recipients received 100% O2 or 98% O2 with 2% N2, 2% He, or 2% H2 during surgery and 1 hr after reperfusion. The effects of hydrogen were assessed by functional, pathologic, and molecular analysis.


RESULTS
Gas exchange was markedly impaired in animals exposed to 100% O2, 2% N2, or 2% He. Hydrogen inhalation attenuated graft injury as indicated by significantly improved gas exchange 2 hr after reperfusion. Graft lipid peroxidation was significantly reduced in the presence of hydrogen, demonstrating antioxidant effects of hydrogen in the transplanted lungs. Lung cold I/R injury causes the rapid production and release of several proinflammatory mediators and epithelial apoptosis. Exposure to 2% H2 significantly blocked the production of several proinflammatory mediators and reduced apoptosis with induction of the antiapoptotic molecules B-cell lymphoma-2 and B-cell lymphoma-extra large.


CONCLUSIONS
Treatment of LTx recipients with inhaled hydrogen can prevent lung I/R injury and significantly improve the function of lung grafts after extended cold preservation, transplant, and reperfusion.
Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Tomohiro
T
Kawamura
Chien-Sheng
CS
Huang
Naobumi
N
Tochigi
Sungsoo
S
Lee
Norihisa
N
Shigemura
Timothy R
TR
Billiar
Meinoshin
M
Okumura
Atsunori
A
Nakao
Yoshiya
Y
Toyoda
D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019254:Genes, bcl-2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006859:Hydrogen / Q000008:administration & dosage / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016040:Lung Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*; D012121:Respiration, Artificial / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014140:Tracheotomy; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D006859:Hydrogen; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases