EFFECT OF PERIOPERATIVE NITRIC OXIDE DELIVERY ON NITROSYL STRESS AND LOCAL INFLAMMATION-MEDIATED TUBULAR KIDNEY INJURY DURING HEMIARCH SURGERY
https://doi.org/10.17802/2306-1278-2025-14-3-40-50
Abstract
Highlights
The organoprotective effect of nitric oxide during cardiac surgery, including reconstructive interventions on the aorta, is widely studied, however, its use may be limited due to the likely development of side effects, including kidney damage. This paper presents data on the study of the possible negative effects of nitric oxide on the kidneys in patients undergoing Hemiarch surgery.
Abstract
Aim. To evaluate the effect of perioperative nitric oxide delivery on the severity of nitrosyl stress and renal tubular injury mediated by local inflammation activation during Hemiarch surgery under conditions of cardiopulmonary bypass and hypothermic circulatory arrest.
Methods. The work presents the data of a single-center, single-blind, prospective, randomized controlled trial. The study included 80 patients over 18 years of age who underwent Hemiarch surgeries under artificial circulation and hypothermic circulatory arrest for non-syndromic ascending aortic aneurysms in the period 2020–2023. All patients were randomized into two groups in a 1:1 ratio: the NO group (main group), which received perioperative delivery of nitric oxide at a concentration of 80 ppm, and the standard perioperative support group (control group, NO delivery was not performed). To assess the severity of NO-mediated nitrosyl stress, the concentration of nitrotyrosine in the blood serum was measured. Blood was sampled immediately after placement of the central venous catheter and 4 hours after the end of the surgery. To assess the severity of renal tubular injury mediated by local inflammation activation, the concentration of IL-18 in urine was determined. Urine was collected after bladder catheterization and 4 hours after the end of surgery.
Results. The concentration of nitrotyrosine 4 hours after surgery was 10.67 [8.99; 12.50] ng/ml in the NO group and 6.74 [5.89; 10.50] ng/ml in the no-NO group (p = 0.13). The concentration of IL-18 in urine 4 hours after surgery was 5.01 [4.06; 5.98] ng/ml in the NO group and 5.82 [3.60; 29.40] ng/ml in the no-NO group (p = 0.50).
Conclusion. Perioperative delivery of 80 ppm NO during Hemiarch surgery under CPB and hypothermic circulatory arrest does not induce NO-mediated nitrosyl stress and does not affect renal tubular injury mediated by local inflammatory activation.
About the Authors
Alexandr M. BoykoRussian Federation
Anesthesiologist-Intensivist, Department of Anesthesiology and Intensive Care, Junior Researcher, Laboratory of Disaster Medicine, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Nikolay O. Kamenshchikov
Russian Federation
PhD, Head of the Laboratory of Disaster Medicine, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Yuriy K. Podoksenov
Russian Federation
MD, Leading Research Scientist, Department of Cardiovascular Surgery, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Julia S. Svirko
Russian Federation
MD, Clinical Laboratory Scientist, Department of Anesthesiology and Intensive Care, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Mariia L. Diakova
Russian Federation
PhD, Research Scientist, Department of Cardiovascular Surgery, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Anna M. Gusakova
Russian Federation
Cand. Sci. (Pharm.), Senior Research Scientist, Department of Clinical Laboratory Diagnostics, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Dmitriy S. Panfilov
Russian Federation
MD, Leading Research Scientist, Department of Cardiovascular Surgery, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
Boris N. Kozlov
Russian Federation
MD, Head of the Department of Cardiovascular Surgery, Cardiology Research Institute, branch of the Federal State Budgetary Scientific Institution “Tomsk National Research Medical Center of the Russian Academy of Sciences”, Tomsk, Russian Federation
References
1. Amano K., Takami Y., Ishikawa H. et al. Lower body ischaemic time is a risk factor for acute kidney injury after surgery for type A acute aortic dissection. Interact Cardiovasc Thorac Surg. 2020;30(1):107-112. doi: 10.1093/icvts/ivz220.
2. Wu H.B., Ma W.G., Zhao H.L. et al. Risk factors for continuous renal replacement therapy after surgical repair of type A aortic dissection. J Thorac Dis. 2017;9(4):1126-1132. doi: 10.21037/jtd.2017.03.128.
3. Wang J., Yu W., Zhai G. et al. Independent risk factors for postoperative AKI and the impact of the AKI on 30-day postoperative outcomes in patients with type A acute aortic dissection: an updated meta-analysis and meta-regression. J Thorac Dis. 2018;10(5):2590-2598. doi: 10.21037/jtd.2018.05.47.
4. Ghincea C.V., Reece T.B., Eldeiry M. et al. Predictors of Acute Kidney Injury Following Aortic Arch Surgery. J Surg Res. 2019;242:40-46. doi: 10.1016/j.jss.2019.03.055.
5. Kozlov B.N., Panfilov D.S., Sonduev E.L., Lukinov V.L. Predictors of early adverse events after ascending aortic replacement. The Siberian Journal of Clinical and Experimental Medicine. 2022;37(1):108–117. (In Russ.). doi: 10.29001/2073-8552-2022-37-1-108-117.
6. Yan Y, Kamenshchikov N, Zheng Z, Lei C. Inhaled nitric oxide and postoperative outcomes in cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis. Nitric Oxide. 2024;146:64-74. doi:10.1016/j.niox.2024.03.004
7. Kamenshchikov, N. O., Podoksenov, Y. K., Kozlov, B. N., et al. The Nephroprotective Effect of Nitric Oxide during Extracorporeal Circulation: An Experimental Study. Biomedicines. 2024;12(6):1298. doi:10.3390/biomedicines12061298
8. Ostermann M, Kunst G, Baker E et al. Cardiac Surgery Associated AKI Prevention Strategies and Medical Treatment for CSA-AKI. J Clin Med. 2021;10(22):5285. doi:10.3390/jcm10225285
9. Nadim MK, Forni LG, Bihorac A, et al. Cardiac and Vascular Surgery-Associated Acute Kidney Injury: The 20th International Consensus Conference of the ADQI (Acute Disease Quality Initiative) Group. J Am Heart Assoc. 2018;7(11):e008834. doi:10.1161/JAHA.118.008834
10. Ostermann M, Liu K. Pathophysiology of AKI. Best Pract Res Clin Anaesthesiol. 2017;31(3):305-314. doi:10.1016/j.bpa.2017.09.001
11. Wang Y, Bellomo R. Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment. Nat Rev Nephrol. 2017;13(11):697-711. doi: 10.1038/nrneph.2017.119.
12. Bro S, Bentzon JF, Falk E, et al. Chronic renal failure accelerates atherogenesis in apolipoprotein E-deficient mice. J Am Soc Nephrol. 2003;14(10):2466-74. doi: 10.1097/01.asn.0000088024.72216.2e. PMID: 14514724.
13. Bellomo R, Auriemma S, Fabbri A, et al. The pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Int J Artif Organs. 2008;31(2):166-178. doi:10.1177/039139880803100210
14. Arellano DL. Acute Kidney Injury Following Cardiothoracic Surgery. Crit Care Nurs Clin North Am. 2019;31(3):407-417. doi:10.1016/j.cnc.2019.05.008
15. Wang J, Cong X, Miao M, et al. Inhaled nitric oxide and acute kidney injury risk: a meta-analysis of randomized controlled trials. Ren Fail. 2021;43(1):281-290. doi:10.1080/0886022X.2021.1873805
16. Kamenshchikov NO, Anfinogenova YJ, Kozlov BN, et al. Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial. J Thorac Cardiovasc Surg. 2022;163(4):1393-1403.e9. doi: 10.1016/j.jtcvs.2020.03.182.
17. Vermeulen Windsant IC, Snoeijs MG, Hanssen SJ, et al. Hemolysis is associated with acute kidney injury during major aortic surgery. Kidney Int. 2010;77(10):913-920. doi:10.1038/ki.2010.24
18. Kamenshchikov NO, Duong N, Berra L. Nitric Oxide in Cardiac Surgery: A Review Article. Biomedicines. 2023;11(4):1085. doi: 10.3390/biomedicines11041085.
19. Hu J, Spina S, Zadek F, et al. Effect of nitric oxide on postoperative acute kidney injury in patients who underwent cardiopulmonary bypass: a systematic review and meta-analysis with trial sequential analysis. Ann Intensive Care. 2019;9(1):129. doi:10.1186/s13613-019-0605-9
20. Ruan SY, Huang TM, Wu HY, et al. Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials. Crit Care. 2015;19(1):137. doi: 10.1186/s13054-015-0880-2.
21. Grebenchikov, O., Filippovskaya, Zh., Zabelina, T., i dr. Opredelenie nitrotirozina ne pozvolyaet ocenit` stepen` vy`razhennosti oksidantnogo stressa i prognozirovat` veroyatnost` razvitiya rannix oslozhnenij posleoperacionnogo perioda. Patologiya krovoobrashheniya i kardioxirurgiya, 21(2), 77–84. (In Russ.). https://doi.org/10.21688/1681-3472-2017-2-77-84
22. Wigner P, Szymańska B, Bijak M, et al. Oxidative stress parameters as biomarkers of bladder cancer development and progression. Sci Rep. 2021;11(1):15134. doi: 10.1038/s41598-021-94729-w.
23. Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007;87(1):315-424. doi: 10.1152/physrev.00029.2006.
24. Kumar S, Saxena J, Srivastava VK, et al. The Interplay of Oxidative Stress and ROS Scavenging: Antioxidants as a Therapeutic Potential in Sepsis. Vaccines (Basel). 2022;10(10):1575. doi: 10.3390/vaccines10101575.
25. Mohiuddin I, Chai H, Lin PH, et al. Nitrotyrosine and chlorotyrosine: clinical significance and biological functions in the vascular system. J Surg Res. 2006;133(2):143-9. doi: 10.1016/j.jss.2005.10.008.
26. Cheng H, Sun JZ, Ji FH, Liu H. Prevention and Treatment of Cardiac Surgery Associated Acute Kidney Injury. J Anesth Perioper Med. 2016;3(1):42-51. PMID: 31598583; PMCID: PMC6785192
27. Liu Y, Guo W, Zhang J, et al. Urinary interleukin 18 for detection of acute kidney injury: a meta-analysis. Am J Kidney Dis. 2013;62(6):1058-67. doi: 10.1053/j.ajkd.2013.05.014.
28. Lin X, Yuan J, Zhao Y, Zha Y. Urine interleukin-18 in prediction of acute kidney injury: a systemic review and meta-analysis. J Nephrol. 2015 Feb;28(1):7-16. doi: 10.1007/s40620-014-0113-9.
29. Hirooka Y, Nozaki Y. Interleukin-18 in Inflammatory Kidney Disease. Front Med (Lausanne). 2021;8:639103. doi: 10.3389/fmed.2021.639103.
30. Liang H, Xu F, Zhang T, et al. Inhibition of IL-18 reduces renal fibrosis after ischemia-reperfusion. Biomed Pharmacother. 2018;106:879-889. doi: 10.1016/j.biopha.2018.07.031.
31. Parikh CR, Coca SG, Thiessen-Philbrook H, et al. TRIBE-AKI Consortium. Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery. J Am Soc Nephrol. 2011;22(9):1748-57. doi: 10.1681/ASN.2010121302.
Supplementary files
Review
For citations:
Boyko A.M., Kamenshchikov N.O., Podoksenov Yu.K., Svirko J.S., Diakova M.L., Gusakova A.M., Panfilov D.S., Kozlov B.N. EFFECT OF PERIOPERATIVE NITRIC OXIDE DELIVERY ON NITROSYL STRESS AND LOCAL INFLAMMATION-MEDIATED TUBULAR KIDNEY INJURY DURING HEMIARCH SURGERY. Complex Issues of Cardiovascular Diseases. 2025;14(3):40-50. (In Russ.) https://doi.org/10.17802/2306-1278-2025-14-3-40-50