Skip to main content

Perioperative Mitigation of Oxidative Stress with Molecular Hydrogen During Simulated Heart Transplantation in Pigs

  • Chapter
  • First Online:
Molecular Hydrogen in Health and Disease

Abstract

Heart transplantation is now a routine method for severe heart failure treatment. It is critical to focus on preventing ischemia–reperfusion damage and mitigating oxidative stress to achieve successful outcomes. However, prolonged anesthesia, hyperoxia, and defibrillations contribute to an increase of ROS/RNS and disrupt the redox homeostasis, which poses a serious risk factor. Numerous publications have confirmed the remarkable antioxidant, anti-apoptotic, and anti-inflammatory properties of molecular hydrogen. In our simulated heart transplantation experiment, we demonstrate that administering 2% hydrogen gas during anesthesia and extracorporeal circulation (ECC) significantly alleviates oxidative stress-induced damage. This is evidenced by a significant decrease in markers of ischemia, lipid peroxidation, and inflammation. The restoration of the pumping activity in the implanted pig hearts showed improvement, with a reduced need for repeated defibrillations. The administration of H2 during graft collection and transplantation significantly enhances the function of the transplanted heart and the overall condition of the recipient. Hydrogen administered by conventional ventilators and ECC oxygenators represents an innovative therapy that can significantly improve current transplantation techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Uto K, Sakamoto S, Que W et al (2019) Hydrogen-rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation. BMC Gastroenterol 19:25. https://doi.org/10.1186/s12876-019-0939-7

    Article  PubMed  PubMed Central  Google Scholar 

  2. Valko M, Leibfritz D, Moncol J et al (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84. https://doi.org/10.1016/j.biocel.2006.07.001

    Article  CAS  PubMed  Google Scholar 

  3. Jeong E-M, Liu M, Sturdy M et al (2012) Metabolic stress, reactive oxygen species, and arrhythmia. J Mol Cell Cardiol 52:454–463. https://doi.org/10.1016/j.yjmcc.2011.09.018

    Article  CAS  PubMed  Google Scholar 

  4. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. https://doi.org/10.1042/BJ20081386

    Article  CAS  PubMed  Google Scholar 

  5. Suleiman M-S, Zacharowski K, Angelini GD (2008) Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics. Br J Pharmacol 153:21–33. https://doi.org/10.1038/sj.bjp.0707526

    Article  CAS  PubMed  Google Scholar 

  6. Krezdorn N, Tasigiorgos S, Wo L et al (2017) Tissue conservation for transplantation. Innov Surg Sci 2:171–187. https://doi.org/10.1515/iss-2017-0010

    Article  PubMed  PubMed Central  Google Scholar 

  7. Shi S, Xue F (2016) Current antioxidant treatments in organ transplantation. Oxid Med Cell Longev 2016:1–9. https://doi.org/10.1155/2016/8678510

    Article  CAS  Google Scholar 

  8. Hicks M, Hing A, Gao L et al (2006) Organ preservation. Methods Mol Biol 333:331–374. https://doi.org/10.1385/1-59745-049-9:331

    Article  PubMed  Google Scholar 

  9. Lee Y-M, Song BC, Yeum K-J (2015) Impact of volatile anesthetics on oxidative stress and inflammation. Biomed Res Int 2015:1–8. https://doi.org/10.1155/2015/242709

    Article  CAS  Google Scholar 

  10. Alleva R, Tomasetti M, Solenghi MD et al (2003) Lymphocyte DNA damage precedes DNA repair or cell death after orthopaedic surgery under general anaesthesia. Mutagenesis 18:423–428. https://doi.org/10.1093/mutage/geg013

    Article  CAS  PubMed  Google Scholar 

  11. Oldman AH, Martin DS, Feelisch M et al (2021) Effects of perioperative oxygen concentration on oxidative stress in adult surgical patients: a systematic review. Br J Anaesth 126:622–632. https://doi.org/10.1016/j.bja.2020.09.050

    Article  CAS  PubMed  Google Scholar 

  12. Rogan F, Funston R, Meenan B, Burke G (2017) 209 Evaluation of acute cardiac damage in a porcine model of defibrillation. Heart 103:A139.1–A139. https://doi.org/10.1136/heartjnl-2017-311726.207

  13. Tan M, Sun X, Guo L et al (2013) Hydrogen as additive of HTK solution fortifies myocardial preservation in grafts with prolonged cold ischemia. Int J Cardiol 167:383–390. https://doi.org/10.1016/j.ijcard.2011.12.109

    Article  PubMed  Google Scholar 

  14. Noda K, Shigemura N, Tanaka Y et al (2013) A novel method of preserving cardiac grafts using a hydrogen-rich water bath. J Hear Lung Transplant 32:241–250. https://doi.org/10.1016/j.healun.2012.11.004

    Article  Google Scholar 

  15. Tao G, Song G, Qin S (2019) Molecular hydrogen: current knowledge on mechanism in alleviating free radical damage and diseases. Acta Biochim Biophys Sin (Shanghai) 51:1189–1197. https://doi.org/10.1093/abbs/gmz121

    Article  CAS  PubMed  Google Scholar 

  16. Ohsawa I, Ishikawa M, Takahashi K et al (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13:688–694. https://doi.org/10.1038/nm1577

    Article  CAS  PubMed  Google Scholar 

  17. Hayashida K, Sano M, Ohsawa I et al (2008) Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischemia–reperfusion injury. Biochem Biophys Res Commun 373:30–35. https://doi.org/10.1016/j.bbrc.2008.05.165

    Article  CAS  PubMed  Google Scholar 

  18. Hayashida K, Sano M, Kamimura N et al (2014) Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management. Circulation 130:2173–2180. https://doi.org/10.1161/CIRCULATIONAHA.114.011848

    Article  CAS  PubMed  Google Scholar 

  19. Matsuoka T, Suzuki M, Sano M et al (2017) Hydrogen gas inhalation inhibits progression to the “irreversible” stage of shock after severe hemorrhage in rats. J Trauma Acute Care Surg 83:469–475. https://doi.org/10.1097/TA.0000000000001620

    Article  CAS  PubMed  Google Scholar 

  20. Lojda Z, Gossrau R, Schiebler TH (1976) Enzym-histochemische Methoden, 1st ed. Springer-Verlag Berlin and Heidelberg GmbH & Co. K, Berlin

    Google Scholar 

  21. Rossello X, Yellon DM (2018) The RISK pathway and beyond. Basic Res Cardiol 113:2. https://doi.org/10.1007/s00395-017-0662-x

    Article  CAS  PubMed  Google Scholar 

  22. Hadebe N, Cour M, Lecour S (2018) The SAFE pathway for cardioprotection: is this a promising target? Basic Res Cardiol 113:9. https://doi.org/10.1007/s00395-018-0670-5

    Article  PubMed  Google Scholar 

  23. Slezak J, Kura B, LeBaron TW et al (2021) Oxidative stress and pathways of molecular hydrogen effects in medicine. Curr Pharm Des 27:610–625. https://doi.org/10.2174/1381612826666200821114016

    Article  CAS  PubMed  Google Scholar 

  24. Ordin PM (1997) Safety standard for hydrogen and hydrogen systems guidelines for hydrogen system. Design, Materials Selection, Operations, Storage, and Transportation No Title

    Google Scholar 

  25. Buchholz BM, Kaczorowski DJ, Sugimoto R et al (2008) Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury. Am J Transplant 8:2015–2024. https://doi.org/10.1111/j.1600-6143.2008.02359.x

    Article  CAS  PubMed  Google Scholar 

  26. Yan M, Yu Y, Mao X et al (2019) Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner. Int Immunopharmacol 71:61–67. https://doi.org/10.1016/j.intimp.2019.03.021

    Article  CAS  PubMed  Google Scholar 

  27. Liu B, Xie Y, Chen J et al (2021) Protective effect of molecular hydrogen following different routes of administration on D-galactose-induced aging mice. J Inflamm Res 14:5541–5550. https://doi.org/10.2147/JIR.S332286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. de Oliveira EP, Burini RC (2012) High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr 4:12. https://doi.org/10.1186/1758-5996-4-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Xie F, Jiang X, Yi Y et al (2022) Different effects of hydrogen-rich water intake and hydrogen gas inhalation on gut microbiome and plasma metabolites of rats in health status. Sci Rep 12:7231. https://doi.org/10.1038/s41598-022-11091-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fujii J, Homma T, Osaki T (2022) Superoxide radicals in the execution of cell death. Antioxidants 11:501. https://doi.org/10.3390/antiox11030501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Barancik M, Kura B, LeBaron TW et al (2020) Molecular and cellular mechanisms associated with effects of molecular hydrogen in cardiovascular and central nervous systems. Antioxidants 9:1281. https://doi.org/10.3390/antiox9121281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Dhein S, Salameh A (2021) Remodeling of cardiac gap junctional cell-cell coupling. Cells 10:2422. https://doi.org/10.3390/cells10092422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Szeiffova Bacova B, Viczenczova C, Andelova K et al (2020) Antiarrhythmic effects of melatonin and omega-3 are linked with protection of myocardial Cx43 topology and suppression of fibrosis in catecholamine stressed normotensive and hypertensive rats. Antioxidants 9:546. https://doi.org/10.3390/antiox9060546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Slezak J, Tribulova N, Ravingerova T, Singal PK (1992) Myocardial heterogeneity and regional variations in response to injury. Lab Invest 67:322–330

    CAS  PubMed  Google Scholar 

  35. Tribulova N, Novakova S, Macsaliova A et al (2002) Histochemical and ultrastructural characterisation of an arrhythmogenic substrate in ischemic pig heart. Acta Histochem 104:393–397. https://doi.org/10.1078/0065-1281-00670

    Article  PubMed  Google Scholar 

  36. Slezák J, Klobusická M (1969) To some questions of early changes of ischemic myocardium. Folia Morphol (Warsz) 17:165–170

    Google Scholar 

  37. Schaper J (1986) Ultrastructural changes of the myocardium in regional ischaemia and infarction. Eur Heart J 7:3–9. https://doi.org/10.1093/eurheartj/7.suppl_B.3

    Article  PubMed  Google Scholar 

  38. Slezak J, Geller SA, Litwak RS, Smith H (1983) Long-term study of the ultrastructural changes of myocardium in patients undergoing cardiac surgery, with more than 10 years follow-up. Int J Cardiol 4:153–168. https://doi.org/10.1016/0167-5273(83)90129-8

    Article  CAS  PubMed  Google Scholar 

Download references

Competing Interest

We thank the management of IKEM Prague for hiring operating rooms and transplant assistants. We thank the collaborating team of the Slovak Institute of Heart Diseases (Drs. M. Hulman, V. Hudec, J. Luptak, I-Olejarova, M. Ondrusek, I. Gasparovic, R.Sramaty) for performing simulated transplantation.

Funding

This research was funded by grants from Slovak Research and Development Agency (APVV-0241–11, APVV-15–0376, APVV-19–0317), grant from the Slovak Academy of Sciences (VEGA 2/0092/22 and 2/0063/18), grant from European Union Structural funds (ITMS 26230120009), grant (2018/7838:1-26C0), and grant from Ministry of Health of The Slovak Republic (2019-CEMSAV-1). Authors declare no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jan Slezak .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kura, B. et al. (2024). Perioperative Mitigation of Oxidative Stress with Molecular Hydrogen During Simulated Heart Transplantation in Pigs. In: Slezak, J., Kura, B. (eds) Molecular Hydrogen in Health and Disease. Advances in Biochemistry in Health and Disease, vol 27. Springer, Cham. https://doi.org/10.1007/978-3-031-47375-3_12

Download citation

Publish with us

Policies and ethics