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.
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References
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
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
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
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13. https://doi.org/10.1042/BJ20081386
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Lojda Z, Gossrau R, Schiebler TH (1976) Enzym-histochemische Methoden, 1st ed. Springer-Verlag Berlin and Heidelberg GmbH & Co. K, Berlin
Rossello X, Yellon DM (2018) The RISK pathway and beyond. Basic Res Cardiol 113:2. https://doi.org/10.1007/s00395-017-0662-x
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
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
Ordin PM (1997) Safety standard for hydrogen and hydrogen systems guidelines for hydrogen system. Design, Materials Selection, Operations, Storage, and Transportation No Title
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
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
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
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
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
Fujii J, Homma T, Osaki T (2022) Superoxide radicals in the execution of cell death. Antioxidants 11:501. https://doi.org/10.3390/antiox11030501
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
Dhein S, Salameh A (2021) Remodeling of cardiac gap junctional cell-cell coupling. Cells 10:2422. https://doi.org/10.3390/cells10092422
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
Slezak J, Tribulova N, Ravingerova T, Singal PK (1992) Myocardial heterogeneity and regional variations in response to injury. Lab Invest 67:322–330
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
Slezák J, Klobusická M (1969) To some questions of early changes of ischemic myocardium. Folia Morphol (Warsz) 17:165–170
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
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
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.
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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
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DOI: https://doi.org/10.1007/978-3-031-47375-3_12
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