Advertisement
The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

A novel method of preserving cardiac grafts using a hydrogen-rich water bath

      Background

      Exogenously administered hydrogen exerts cytoprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in various disease settings, including organ transplantation. Our objective in this study was to evaluate the efficacy of a novel cold storage device equipped with a hydrogen-rich water bath.

      Methods

      The study used an established rat heterotopic transplantation model. Syngeneic heart grafts from elderly donors (60- to 70-week-old Lewis rats) or allografts from adult donors (12-week-old Brown Norway rats) were exposed to prolonged cold preservation. The cardiac grafts were stored in plastic bags containing Celsior, which were immersed in the cold water bath equipped with an electrolyzer to saturate the water with hydrogen. The cardiac grafts then were heterotopically engrafted into Lewis rat recipients.

      Results

      In both experimental settings, serum troponin I and creatine phosphokinase were markedly elevated 3 hours after reperfusion in the control grafts without hydrogen treatment. The grafts exhibited prominent inflammatory responses, including neutrophil infiltration and the upregulation of messenger RNAs for pro-inflammatory cytokines and chemokines. Myocardial injury and inflammatory events were significantly attenuated by organ storage in the hydrogen-rich water bath. The grafts stored using the hydrogen-rich water bath also exhibited less mitochondrial damage and a higher adenosine triphosphate content.

      Conclusions

      Hydrogen delivery to cardiac grafts during cold preservation using a novel hydrogen-supplemented water bath efficiently ameliorated myocardial injury due to cold ischemia and reperfusion. This new device to saturate organs with hydrogen during cold storage merits further investigation for possible therapeutic and preventative use during transplantation.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Heart and Lung Transplantation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lutz J.
        • Thürmel K.
        • Heemann U.
        Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation.
        J Inflam. 2010; 7: 27
        • Land W.G.
        The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation.
        Transplantation. 2005; 79: 505-514
        • Ohsawa I.
        • Ishikawa M.
        • Takahashi K.
        • et al.
        Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.
        Nat Med. 2007; 13: 688-694
        • Huang C.S.
        • Kawamura T.
        • Toyoda Y.
        • Nakao A.
        Recent advances in hydrogen research as a therapeutic medical gas.
        Free Radic Res. 2010; 44: 971-982
        • Fukuda K.I.
        • Asoh S.
        • Ishikawa M.
        • Yamamoto Y.
        • Ohsawa I.
        • Ohta S.
        Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress.
        Biochem Biophys Res Commun. 2007; 361: 670-674
        • Hayashida K.
        • Sano M.
        • Ohsawa I.
        • et al.
        Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia-reperfusion injury.
        Biochem Biophys Res Commun. 2008; 373: 30-35
        • Xie K.
        • Yu Y.
        • Pei Y.
        • et al.
        Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release.
        Shock. 2010; 34: 90-97
        • Huang C.S.
        • Kawamura T.
        • Lee S.
        • et al.
        Hydrogen inhalation ameliorates ventilator-induced lung injury.
        Critical Care. 2010; 14: R234
        • Kawamura T.
        • Huang C.S.
        • Tochigi N.
        • et al.
        Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats.
        Transplantation. 2010; 90: 1344-1351
        • Buchholz B.M.
        • Kaczorowski D.J.
        • Sugimoto R.
        • et al.
        Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury.
        Am J Transplant. 2008; 8: 2015-2024
        • Nakao A.
        • Kaczorowski D.J.
        • Wang Y.
        • et al.
        Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both.
        J Heart Lung Transplant. 2010; 29: 544-553
        • Kawamura T.
        • Huang C.S.
        • Peng X.
        • et al.
        The effect of donor treatment with hydrogen on lung allograft function in rats.
        Surgery. 2011; 150: 240-249
        • Buchholz B.M.
        • Masutani K.
        • Kawamura T.
        • et al.
        Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation.
        Transplantation. 2011; 92: 985-992
        • Lee S.
        • Huang C.S.
        • Kawamura T.
        • et al.
        Histidine-tryptophan-ketoglutarate or Celsior: which is more suitable for cold preservation for cardiac grafts from older donors?.
        Ann Thorac Surg. 2011; 91: 755-763
        • Nakao A.
        • Toyokawa H.
        • Abe M.
        • et al.
        Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and alloreactive T-cell responses.
        Transplantation. 2006; 81: 220-230
        • Nakao A.
        • Toyoda Y.
        • Sharma P.
        • Evans M.
        • Guthrie N.
        Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study.
        J Clin Biochem Nutr. 2010; 46: 140-149
        • Sun Q.
        • Kawamura T.
        • Masutani K.
        • et al.
        Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats.
        Cardiovasc Res. 2012; 94: 144-153
        • Lee S.
        • Huang C.S.
        • Kawamura T.
        • et al.
        Superior myocardial preservation with HTK solution over Celsior in rat hearts with prolonged cold ischemia.
        Surgery. 2010; 148: 463-473
        • Cardinal J.S.
        • Zhan J.
        • Wang Y.
        • et al.
        Oral hydrogen water prevents chronic allograft nephropathy in rats.
        Kidney Intl. 2010; 77: 101-109
        • Nakao A.
        • Kimizuka K.
        • Stolz D.B.
        • et al.
        Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury.
        Am J Pathol. 2003; 163: 1587-1598
        • Kohmoto J.
        • Nakao A.
        • Kaizu T.
        • et al.
        Low-dose carbon monoxide inhalation prevents ischemia/reperfusion injury of transplanted rat lung grafts.
        Surgery. 2006; 140: 179-185
        • Stangl V.
        • Baumann G.
        • Stangl K.
        • Felix S.B.
        Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion.
        Cardiovasc Res. 2002; 53: 12-30
        • Kim J.S.
        • He L.
        • Lemasters J.J.
        Mitochondrial permeability transition: a common pathway to necrosis and apoptosis.
        Biochem Biophys Res Commun. 2003; 304: 463-470
        • Zhao Z.Q.
        • Vinten-Johansen J.
        Myocardial apoptosis and ischemic preconditioning.
        Cardiovasc Res. 2002; 55: 438-455
        • Kapadia S.
        • Lee J.
        • Torre-Amione G.
        • Birdsall H.H.
        • Ma T.S.
        • Mann D.L.
        Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration.
        J Clin Invest. 1995; 96: 1042-1052
        • Ishii D.
        • Schenk A.D.
        • Baba S.
        • Fairchild R.L.
        Role of TNFalpha in early chemokine production and leukocyte infiltration into heart allografts.
        Am J Transplant. 2010; 10: 59-68
        • Piantadosi C.A.
        • Carraway M.S.
        • Babiker A.
        • Suliman H.B.
        Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1.
        Circ Res. 2008; 103: 1232-1240
        • Macgarvey N.C.
        • Suliman H.B.
        • Bartz R.R.
        • et al.
        Activation of mitochondrial biogenesis by heme oxygenase-1-mediated NF-E2-related factor-2 induction rescues mice from lethal Staphylococcus aureus sepsis.
        Am J Respir Crit Care Med. 2012; 185: 851-861
        • Lesnefsky E.J.
        • Moghaddas S.
        • Tandler B.
        • Kerner J.
        • Hoppel C.L.
        Mitochondrial dysfunction in cardiac disease: ischemia—reperfusion , aging, and heart failure.
        J Mol Cell Cardiol. 2001; 33: 1065-1089
        • Wu Z.
        • Puigserver P.
        • Andersson U.
        • et al.
        Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1.
        Cell. 1999; 98: 115-124
        • Podesser B.
        • Wollenek G.
        • Windischbauer A.
        • et al.
        Myocardial protection with Bretschneider cardioplegic solution—an evaluation of full oxygenation.
        Eur Surg Res. 1994; 26: 133-140
        • Irani Y.
        • Pype J.L.
        • Martin A.R.
        • et al.
        Noble gas (argon and xenon)-saturated cold storage solutions reduce ischemia-reperfusion injury in a rat model of renal transplantation.
        Nephron Extra. 2011; 1: 272-282
        • Suszynski T.M.
        • Rizzari M.D.
        • Scott 3rd, W.E.
        • Tempelman L.A.
        • Taylor M.J.
        • Papas K.K.
        Persufflation (or gaseous oxygen perfusion) as a method of organ preservation.
        Cryobiology. 2012; 64: 125-143
        • Moody B.F.
        • Calvert J.W.
        Emergent role of gasotransmitters in ischemia-reperfusion injury.
        Med Gas Res. 2011; 1: 3
        • Nakao A.
        • Faleo G.
        • Shimizu H.
        • et al.
        Ex vivo carbon monoxide prevents cytochrome P450 degradation and ischemia/reperfusion injury of kidney grafts.
        Kidney Int. 2008; 74: 1009-1016
        • Nakao A.
        • Toyokawa H.
        • Tsung A.
        • et al.
        Ex vivo application of carbon monoxide in University of Wisconsin solution to prevent intestinal cold ischemia/reperfusion injury.
        Am J Transplant. 2006; 6: 2243-2255
        • Gupta D.
        • Piacentino 3rd, V.
        • Macha M.
        • et al.
        Effect of older donor age on risk for mortality after heart transplantation.
        Ann Thorac Surg. 2004; 78: 890-899