The effect of nitric oxide donation on the severity of mitochondrial disfunction to the renal tissue in cardiopulmonary bypass simulation: an experimental study
Issue 4 (2023) , FUNDAMENTAL ISSUES IN INTENSIVE CARE
Issue 4 (2023)
FUNDAMENTAL ISSUES IN INTENSIVE CARE

The effect of nitric oxide donation on the severity of mitochondrial disfunction to the renal tissue in cardiopulmonary bypass simulation: an experimental study

https://doi.org/10.21320/1818-474X-2023-4-176-184
Published 30.10.2023
Mark A. Tyo
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
https://orcid.org/0000-0003-2672-6136
N.O. Kamenshchikov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
https://orcid.org/0000-0003-4289-4439
Yu.K. Podoksenov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
https://orcid.org/0000-0002-8939-2340
A.V. Mukhomedzyanov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
https://orcid.org/0000-0003-1808-556X
L.N. Maslov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
https://orcid.org/0000-0002-6020-1598
B.N. Kozlov
Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
https://orcid.org/0000-0002-0217-7737
PDF_2023-4_176-184 (Русский)

Keywords

nitric oxide
acute kidney injury
mitochondria
cardiopulmonary bypass

How to Cite

Tyo M.A., Kamenshchikov N.O., Podoksenov Y.K., Mukhomedzyanov A.V., Maslov L.N., Kozlov B.N. The effect of nitric oxide donation on the severity of mitochondrial disfunction to the renal tissue in cardiopulmonary bypass simulation: an experimental study. Annals of Critical Care. 2023;(4):176–184. doi:10.21320/1818-474X-2023-4-176-184.
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver AMA GOST

Download Citation

Endnote/Zotero/Mendeley (RIS) BibTeX

Statistic

Abstract Views: 143
PDF_2023-4_176-184 (Русский) Downloads: 63
Statistic from 21.01.2023

Language

English Русский

Announcements

Social Networks

Abstract

INTRODUCTION: Acute kidney injury is one of the common complications in cardiosurgical operations with cardiopulmonary bypass (CPB). A number of studies have shown that donation of exogenous nitric oxide (NO) reduces episodes of аcute kidney injury. However, subcellular mechanisms of realization the nephroprotective properties of NO remain unknown. OBJECTIVE: To study the safety of the technology of plasma-chemical synthesis of nitric oxide and to evaluate the effect of the delivery resulting nitric oxide on mitochondrial damage to the renal tissue in the simulation of cardiopulmonary bypass. MATERIALS AND METHODS: Experiment included 12 rams of the Altai breed. Animals were divided into 2 groups: 6 animals were modeled CPB; 6 animals were simulated CPB with NO delivery. Mitochondrial damage was assessed by calcium-binding capacity and transmembrane potential of mitochondria 1 h after weaning from the CPB. The safety of the NO delivery according to the proposed method was assessed by the concentration of nitrogen dioxide on inspiration, the level of methemoglobin. The efficiency of NO delivery according to the proposed method was assessed by the level of stable NO metabolites: endogenous nitrite, nitrate and total concentration of NO metabolites. RESULTS: In the group of animals with NO delivery the average level of transmembrane potential of mitochondria was (171.66 ± 20.41 vs 126.66 ± 18.61; p = 0.00256) and calcium-binding capacity of mitochondria was (1466.66 ± 216.02 vs 866.66 ± 216.02; p = 0.000712) of renal parenchyma. Methemoglobin levels above the recommended thresholds in clinical practice were not recorded in the CPB+NO group. The values of total concentration of NO metabolites and nitrate in the CPB+NO group compared to the CPB group are statistically significantly higher, p = 0.00006; p = 0.0035, respectively. CONCLUSIONS: Plasma-chemical synthesis of nitric oxide is a safe technology, and the use of the resulting nitric oxide in cardiopulmonary bypass leads to a decrease in the severity of mitochondrial dysfunction in the kidney parenchyma.

https://doi.org/10.21320/1818-474X-2023-4-176-184
PDF_2023-4_176-184 (Русский)

Full-text of the article is available for this locale: Русский.

References

  1. Бокерия Л.А. Современные тенденции развития сердечно-сосудистой хирургии (20 лет спустя). Анналы хирургии. 2016; 21(1–2): 10–9. DOI: 10.18821/1560-9502-2016-21-1-10-18 [Bockeria L.A. Modern trends in the development of cardiovascular surgery. Annals of Surgery, Russian journal. 2016; 21(1–2): 10–9. DOI: 10.18821/1560-9502-2016-21-1-10-18 (In Russ)]
  2. Kumar A.B., Suneja M., Riou B. Cardiopulmonary bypass-associated acute kidney injury. Anesthesiology. 2011; 114(4): 964–70. DOI: 10.1097/aln.0b013e318210f86a
  3. Huen S.C., Parikh C.R. Predicting acute kidney injury after cardiac surgery: A systematic review. Ann Thorac Surg. 2012; 93(1): 337–47. DOI: 10.1016/j.athoracsur.2011.09.010
  4. Billings F.T., Pretorius M., Schildcrout J.S., et al. Obesity and oxidative stress predict AKI after cardiac surgery. Clin J Am Soc Nephrol. 2012; 23(7): 1221–8. DOI: 10.1681/asn.2011090940
  5. O’Neal J.B., Shaw A.D., Billings F.T. Acute kidney injury following cardiac surgery: Current understanding and future directions. Crit Care. 2016; 20(1): 187. DOI: 10.1186/s13054-016-1352-z
  6. Kertai M.D., Zhou S., Karhausen J.A., et al. Platelet counts, acute kidney injury, and mortality after coronary artery bypass grafting surgery. Anesthesiology. 2016; 124(2): 339–52. DOI: 10.1097/aln.0000000000000959
  7. Lei C., Berra L., Rezoagli E., 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
  8. Bedford M., Stevens P.E., Wheeler T.W.K., Farmer C.K.T. What is the real impact of acute kidney injury? BMC Nephrol. 2014; 15(1): 95. DOI: 10.1186/1471-2369-15-95
  9. Hobson C.E., Yavas S., Segal M.S., et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation. 2009; 119(18): 2444–53. DOI: 10.1161/circulationaha.108.800011
  10. 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): 166–78. DOI: 10.1177/039139880803100210
  11. Al-Otaibi K.E., Al Elaiwi A.M., Tariq M., et al. Simvastatin attenuates contrast-induced nephropathy through modulation of oxidative stress, proinflammatory myeloperoxidase, and nitric oxide. Oxid Med Cell Longev. 2012; 2012: 1–8. DOI: 10.1155/2012/831748
  12. Andrade L., Campos S.B., Seguro A.C. Hypercholesterolemia aggravates radiocontrast nephrotoxicity: Protective role of L-arginine. Kidney Int. 1998; 53(6): 1736–42. DOI: 10.1046/j.1523-1755.1998.00906.x
  13. Kamenshchikov N.O., Anfinogenova Y.J., Kozlov B.N., et al. Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial. J Thorac Cardiovasc Surg. 2022; 163(4): 1393–403. DOI: 10.1016/j.jtcvs.2020.03.182
  14. Göthberg S., Edberg K.E. Inhaled nitric oxide to newborns and infants after congenital heart surgery on cardiopulmonary bypass: A dose-response study. Scand Cardiovasc J. 2000; 34(2): 154–8. DOI: 10.1080/14017430050142161
  15. Miller C., Miller M., McMullin B., et al. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012; 11(4): 324–31. DOI: 10.1016/j.jcf.2012.01.003
  16. Young J.D., Dyar O., Xiong L., Howell S. Methaemoglobin production in normal adults inhaling low concentrations of nitric oxide. Intensive Care Medicine. 1994; 20(8): 581–4. DOI: 10.1007/bf01705726
  17. Lehninger A.L. Biochemistry: The Molecular Basis of Cell Structure and Function (Second Edition). New York: Worth Publishers. 1978; 1104 p.
  18. Сенокосова Е.А., Крутицкий С.С., Груздева О.В. и др. Исследование антиоксидантного эффекта митохондриально-направленного антиоксиданта SkQ1 на модели изолированного сердца крысы. Общая реаниматология. 2022; 18(4): 36–44. DOI: 10.15360/1813-9779-2022-4-36-44 [Senokosova E.A., Krutitsky S.S., Gruzdev O.V., et al. The Antioxidant Effect of Mitochondrially Targeted Antioxidant SkQ1 on the Isolated Rat Heart Model. General Reanimatology. 2022; 18(4): 36–44. DOI: 10.15360/1813-9779-2022-4-36-44 (In Russ)]
  19. Северин Е.С. Биологическая химия. М.: ГЭОТАР-Медиа, 2011. 624 с. [Severin E.S. Biologicheskaya himiya. M.: GEOTAR-Media, 2011. 624 p. (In Russ)]
  20. Белослудцев К.Н., Дубинин М.В., Белослудцева Н.В., Миронова Г.Д. Транспорт ионов Ca2+ митохондриями: механизмы, молекулярные структуры и значение для клетки. Биохимия. 2019; 84(6): 759–75. DOI: 10.1134/s0320972519060022 [Belosludcev K.N., Dubinin M.V., Belosludceva N.V., Mironova G.D. Mitochondrial Ca2+ transport: mechanisms, molecular structures, and a significance for cells. Biochemistry (Moscow). 2019; 84(6): 759–75. DOI: 10.1134/s0320972519060022 (In Russ)]
  21. Nicholls D.G., Ferguson S.J. Bioenergetics Fourth Edition. New York: Academic Press, 2013. 434 p. ISBN 9780123884251
  22. Piper H.M., Balser C., Ladilov Y.V., et al. The role of NA+/H+ exchange in ischemia-reperfusion. Basic Res Cardiol. 1996; 91(3): 191–202. DOI: 10.1007/bf00788905
  23. Murphy E., Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev. 2008; 88(2): 581–609. DOI: 10.1152/physrev.00024.2007
  24. Naryzhnaya N.V., Maslov L.N., Oeltgen P.R. Pharmacology of mitochondrial permeability transition pore inhibitors. Drug Dev Res. 2019; 80(8): 1013–30. DOI: 10.1002/ddr.21593
  25. Shvedova M., Anfinogenova Y., Popov S.V., Atochin D.N. Connexins and nitric oxide inside and outside mitochondria: Significance for cardiac protection and adaptation. Frontiers in Physiology. 2018; 9(479). DOI: 10.3389/fphys.2018.00479
  26. Guo R., Si R., Scott B.T., Makino A. Mitochondrial Connexin40 regulates mitochondrial calcium uptake in coronary endothelial cells. Am J Physiol Cell Physiol. 2017; 312(4): 398–406. DOI: 10.1152/ajpcell.00283.2016
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Copyright (c) 2023 Annals of Critical Care