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The corrective effect of nitric oxide and molecular hydrogen on parameters of myocardial and endothelial dysfunction in the prevention of multiple organ failure in cardiac surgery patients

https://doi.org/10.29413/ABS.2026-11.4.5

Abstract

Background. Cardiac surgery and cardiopulmonary bypass (CPB) cause ischemia-reperfusion injury, leading to endothelial dysfunction, systemic inflammation and, in some cases, multiple organ failure (MOF), which worsens the prognosis.

Aim. To study the effect of nitric oxide (NO) and molecular hydrogen (H2) on endothelial dysfunction, myocardial contractility during surgery, and postoperative multiple organ failure.

Materials and methods. The study included 123 patients randomized into 4 groups: 1st (n = 30) – control; 2nd (n = 33) – isolated supply of NO (40 ppm) in the CPB circuit; 3rd (n = 30) – isolated supply of H2 (2 vol%) into the CPB circuit; 4th (n = 30) – combined supply of NO (40 ppm) and H2 (2 vol%) into the CPB circuit. During surgery, the functional parameters of the heart were studied using transesophageal echocardiography; the state of endothelial cells – by analysis of circulating endothelial cells (CECs); after surgery – biochemical blood parameters and clinical outcomes.

Results. The action of NO and H2 improved the contractile function of the myocardium, reduced the increase in AST and ALT activity, reduced the urea content compared with the control, maintaining bilirubin (with the combined action of gases) and creatinine within the initial values, which indicates a multi-organ protective effect. Against the background of the action of NO and H2, a more pronounced decrease in circulating endothelial cells was noted, associated with a lower incidence of postoperative complications and MOF. The combined use of NO and H2 caused a multi-organ protective effect superior to the effect of each gas.

Conclusion. Extracorporeal administration of NO and H2 is an effective strategy for correcting myocardial and endothelial dysfunction, which helps prevent the development of multiple organ failure in cardiac surgery patients.

About the Authors

A. V. Deryugina
Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education
Russian Federation

Anna V. Deryugina – Dr. Sc. (Biol.), professor, head of the Department of Physiology and Anatomy

Gagarin Ave, 23, Nizhny Novgorod 60302



V. V. Pichugin
Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education; Privolzhsky Research Medical University of the Ministry of Healthcare of the Russian Federation; Research Institute – Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev
Russian Federation

Vladimir V. Pichugin – Dr. Sc. (Med.), Professor, Department of Anesthesiology, Resuscitation and Transfusiology, Privolzhsky Research Medical University; Chief Researcher of the Department of Physiology and Anatomy, Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education; anesthesiologist–intensivist of the Anesthesiology and Intensive Care Unit, Science Research Institute – Specialized Clinical Cardiosurgical Hospital named after B.A. Korolev

Gagarin Ave, 23, Nizhny Novgorod 60302,

Minin and Pozharsky Square, 10/1, Nizhny Novgorod 603005,

Vaneev str., 209, Nizhny Novgorod 603950



A. V. Bogush
Research Institute – Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev
Russian Federation

Antonina V. Bogush – Cand. Sc. (Med.), anesthesiologist – intensivist, head of the Department of Resuscitation and Intensive Care, Surgeon, Science 

Vaneev str., 209, Nizhny Novgorod 603950



A. V. Polozova
Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education
Russian Federation

Anastasia V. Polozova – Cand. Sc. (Biol.), associate professor, associate professor of the Department of Physiology and Anatomy

Gagarin Ave, 23, Nizhny Novgorod 60302



E. A. Knyazeva
Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education
Russian Federation

Ekaterina A. Knyazeva – master of science of the Department of Physiology and Anatomy

Gagarin Ave, 23, Nizhny Novgorod 60302



E. V. Taranov
Research Institute – Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev
Russian Federation

Evgeny V. Taranov – Cand. Sc. (Med.), anesthesiologist – intensivist of the Anesthesiology and Intensive Care Unit, Science 

Vaneev str., 209, Nizhny Novgorod 603950



S. A. Zhilyayev
Privolzhsky Research Medical University of the Ministry of Healthcare of the Russian Federation; Research Institute – Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev
Russian Federation

Sergey A. Zhilyaev – Postgraduate student at the Department of Anesthesiology, Intensive Care, and Transfusiology Privolzhsky Research Medical University of the Ministry of Healthcare of the Russian Federation; anesthesiologist – intensivist of the Anesthesiology and Intensive Care Unit, Science Research Institute – Specialized Clinical Cardiosurgical Hospital named after B.A. Korolev

Minin and Pozharsky Square, 10/1, Nizhny Novgorod 603005,

Vaneev str., 209, Nizhny Novgorod 603950



I. A. Pakhomov
Research Institute – Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev
Russian Federation

Ilya A. Pakhomov – anesthesiologist – intensivist of the Anesthesiology and Intensive Care Unit, Science 

Vaneev str., 209, Nizhny Novgorod 603950



M. N. Talamanova
Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education
Russian Federation

Maria N. Talamanova – Cand. Sc. (Biol.), associate professor, associate professor of the Department of Physiology and Anatomy

Gagarin Ave, 23, Nizhny Novgorod 603022



D. A. Danilova
Lobachevsky State University of Nizhny Novgorod, Ministry of Science and Higher Education
Russian Federation

Darya A. Danilova – senior lecturer of the Department of Physiology and Anatomy

Gagarin Ave, 23, Nizhny Novgorod 603022



Yu. D. Brichkin
Research Institute – Specialized Cardiac Surgery Clinical Hospital named after Academician B.A. Korolev
Russian Federation

Yuriy D. Brichkin – Dr. Sc. (Med.), consulting professor, Science 

Vaneev str., 209, Nizhny Novgorod 603950



References

1. Velho TR, Pereira RM, Guerra NC, Ferreira R, Pedroso D, Neves-Costa A, et al. The impact of cardiopulmonary bypass time on the Sequential Organ Failure Assessment score after cardiac surgery. Interdiscip Cardiovasc Thorac Surg. 2024; 38(5): ivae082. doi: 10.1093/icvts/ivae082

2. Mamedov E.A., Anikin I.V. Multiple organ failure: current state of the problem and the prospects research. Bulletin of Science. 2025; 6(87–1). (In Russ.).

3. Barbarash LS, Grigoriev EV, Plotnikov GP, Haes BL, Moiseenkov GV, Shukevich DL, et al. Multiple Organ Failure After Cardiac Surgery Interventions. General Reanimatology. 2010; 5: 31. (In Russ.). doi: 10.15360/1813-9779-2010-5-31

4. Krichevsky LA, Rybakov VYu, Dvoryadki AA, Protsenko DN. Systemic Inflammatory Response in Cardiac Surgery. Anesthesiology and Resuscitology. 2021; 3: 94–102. (In Russ.). doi: 10.17116/anaesthesiology202103194

5. Viikinkoski E, Aittokallio J, Lehto J, Ollila H, Relander A, Vasankari T, et al. Prolonged Systemic Inflammatory Response Syndrome After Cardiac Surgery. J Cardiothorac Vasc Anesth. 2024; 38(3): 709–716. doi: 10.1053/j.jvca.2023.12.017

6. Ayıkgöz Y, Salih Aydın M, Kankılıç N, Temiz E. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Tumor Necrosis Factor Alpha Protein (TNF-α), Heme Oxygenase-1 (HO-1) Gene Expressions during Cardiopulmonary Bypass. Gene. 2021; 790: 145690. doi: 10.1016/j.gene.2021.145690

7. Mallat J, Rahman N, Hamed F, Hernandez G, Fischer MO. Pathophysiology, mechanisms, and managements of tissue hypoxia. Anaesth Crit Care Pain Med. 2022; 41(4): 101087. doi: 10.1016/j.accpm.2022.101087

8. Cherry AD. Mitochondrial Dysfunction in Cardiac Surgery. Anesthesiol Clin. 2019; 37(4): 769–785. doi: 10.1016/j.anclin.2019.08.003

9. Zhang J, Zhang H, Wang J, Wang T, Bian L, Li Zh, et al. The organ-protective effects of nitric oxide in adult patients undergoing cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis. BMC Anesthesiol. 2025; 25(1): 335. doi: 10.1186/s12871-025-03207-7

10. Chuchalin AG. Nitric oxide – a molecule of the 21st century. Pulmonology. 2024; 34(3): 326–335. (In Russ.). doi: 10.18093/0869-0189-2024-34-3-326-333

11. Lei C, Berra L, Rezoagli E, Yu B, Dong H, Yu S, et al. Nitric oxide decreases acute kidney injury and stage 3 chronic kidney disease after cardiac surgery. Am J Respir Crit Care Med. 2018; 198(10): 1279–87. doi: 10.1164/rccm.201710-2150OC

12. Kamenshchikov NO, Anfinogenova YJ, Kozlov BN, Svirko YS, Pekarskiy SE, Evtushenko VV, et al. Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial. J Thorac Cardiovasc Surg. 2022; 163(4): 1393–1403e9. doi: 10.1016/j.jtcvs.2020.03.182

13. Jin J, Yue L, Du M, Geng F, Gao X, Zhou Y, et al. Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application. Med Comm 2025; 6(5): e70194. doi: 10.1002/mco2.70194

14. Danilova DA, Brichkin YuD, Medvedev AP, Pichugin VV, Fedorov SA, Taranov EV, et al. Application of molecular hydrogen in heart surgery under cardiopulmonary bypass. Modern Technologies in Medicine. 2021; 13(1): 71–77. (In Russ.). doi: 10.17691/stm2021.13.1.09

15. Deryugina AV, Danilova DA. Molecular hydrogen reduces the degree of endothelial alteration in conditions of chronic heart failure. Bulletin of Experimental Biology and Medicine. 2023;175(4): 433–436. (In Russ.). doi: 10.47056/0365-9615-2023-175-4-426-429

16. Hu D, Kabayama S, Watanabe Y, Cui Y. Health Benefits of Electrolyzed Hydrogen Water: Antioxidant and Anti-Inflammatory Effects in Living Organisms. Antioxidants (Basel). 2024; 13(3): 313. doi: 10.3390/antiox13030313

17. Sim M, Kim CS, Shon WJ, Lee YK, Choi EY, Shin DM. Hydrogen-rich water reduces inflammatory responses and prevents apoptosis of peripheral blood cells in healthy adults: a randomized, double-blind, controlled trial. Sci. Rep. 2020; 10(1): 12130. doi: 10.1038/s41598-020-68930-2

18. Di Martino ML, Frau A, Losa F, Muggianu E, Mura MN, Rotta G, et al. Role of circulating endothelial cells in assessing the severity of systemic sclerosis and predicting its clinical worsening. Sci Rep. 2021; 11(1): 2681. doi: 10.1038/s41598-020-80604-7

19. Ndrepepa G. Aspartate aminotransferase and cardiovascular disease — a narrative review. J Lab Precis Med. 2021; 6: 6. doi: 10.21037/jlpm-20-93

20. Ndrepepa G, Kastrati A. Alanine aminotransferase — a marker of cardiovascular risk at high and low activity levels. J Lab Precis Med. 2019; 4: 29. doi: 10.21037/jlpm.2019.08.01

21. Dvořák A, Pospíšilová K, Žížalová K, Capková N, Muchová L, Vecka M, et al. The Effects of Bilirubin and Lumirubin on Metabolic and Oxidative Stress Markers. Front. Pharmacol. 2021; 12: 567001. doi: 10.3389/fphar.2021.567001

22. Paulus MC, Melchers M, van Es A, Kouw IWK, van Zanten ARH. The urea-to-creatinine ratio as an emerging biomarker in critical care: a scoping review and meta-analysis. Crit Care. 2025; 29(1): 175. doi: 10.1186/s13054-025-05396-6

23. Chang L, Jia L, Xu Y, Qian Y, Zhao S, Sun Y, et al. Association of Arterial PaCO2 with the Survival of Mechanically Ventilated Patients with Acute Respiratory Failure: A Multicenter Retrospective Cohort Study. Diagnostics. 2026; 16(3): 489. doi: 10.3390/diagnostics16030489

24. Gazizova VP, Vlasova EE, Shiryaev AA, Akchurin RS. Acute heart failure in surgery of coronary artery disease. Russian Cardiology Bulletin. 2022; 17(3): 513. (In Russ.). doi: 10.17116/Cardiobulletin2022170315

25. Nicolotti D, Grossi S, Nicolini F, Gallingani A, Rossi S. Difficult Respiratory Weaning after Cardiac Surgery: A Narrative Review. J Clin Med. 2023; 12(2): 497. doi: 10.3390/jcm12020497

26. Rodrigo R, González-Montero J, Sotomayor CG. Novel combined antioxidant strategy against hypertension, acute myocardial infarction and postoperative atrial fibrillation. Biomedicines. 2021; 9(6): 620. doi: 10.3390/biomedicines9060620

27. Knyazeva EA, Deryugina AV, Yastrebov PV, Boyarinov GА. Biochemical blood counts in the application of fish oil preparations in conditions of intense physical activity. The Scientific Notes of the Pavlov University. 2025; 32(1): 69–78. (In Russ.). doi: 10.24884/1607-4181-2025-32-1-69-78

28. Dekker NAM, van Leeuwen ALI, van Strien WWJ, Majolée J, Szulcek R, Vonk ABA, et al. Microcirculatory perfusion disturbances following cardiac surgery with cardiopulmonary bypass are associated with in vitro endothelial hyperpermeability and increased angiopoietin-2 levels. Crit Care. 2019; 23(1): 117. doi: 10.1186/s13054-019-2418-5

29. Azem K, Novakovsky D, Krasulya B, Fein S, Iluz-FreundlichD, Uhanova J, et al. Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial. Eur J Anaesthesiol. 2024; 41(9): 677–86. doi: 10.1097/EJA.0000000000002022

30. Lundberg JO, Weitzberg E. Nitric oxide signaling in health and disease. Cell. 2022; 185(16): 2853–2878. doi: 10.1016/j.cell.2022.06.010

31. Obara CJ, Nixon-Abell J, Moore AS, Riccio F, HoffmanD, ShtengelG, et al. Motion of VAPB Molecules Reveals ER–mitochondria Contact Site Subdomains. Nature. 2024; 626(7997): 169–176. doi: 10.1038/s41586-023-06956-y

32. Geng N, Gao X, Wang X, Cui Sh, Wang J, Liu Y, et al. Hydrogen helps to ameliorate staphylococcus aureus-induced mastitis in mice. International Immunopharmacology. 2022; 109: 108940. doi: 10.1016/j.intimp.2022.108940

33. Zhang Y, Chen J, Wu H, Li L, Yang X, Lai K, et al. Hydrogen regulates mitochondrial quality to protect glial cells and alleviates sepsis-associated encephalopathy by Nrf2/YY1 complex promoting HO-1 expression. International Immunopharmacology. 2023; 118: 110009. doi: 10.1016/j.intimp.2023.110009

34. Tu M, Fan X, Shi J, Jing S, Xu X, Wang Y. 2-Fluorofucose attenuates hydrogen peroxide-induced oxidative stress in HepG2 cells via Nrf2/keap1 and NF-κB signaling pathways. Life. 2022; 12(3): 406. doi: 10.3390/life12030406


Review

For citations:


Deryugina A.V., Pichugin V.V., Bogush A.V., Polozova A.V., Knyazeva E.A., Taranov E.V., Zhilyayev S.A., Pakhomov I.A., Talamanova M.N., Danilova D.A., Brichkin Yu.D. The corrective effect of nitric oxide and molecular hydrogen on parameters of myocardial and endothelial dysfunction in the prevention of multiple organ failure in cardiac surgery patients. Acta Biomedica Scientifica. 2026;11(4):38-48. (In Russ.) https://doi.org/10.29413/ABS.2026-11.4.5

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