RAS BiologyБиофизика Biophysics

  • ISSN (Print) 0006-3029
  • ISSN (Online) 3034-5278

The Impact of Normacor and Gelofusin Combination on the Preservation of an Isolated Rat Heart during Pressurized Gaseous Hypothermic Storage with Carbon Monoxide and Oxygen Mixture

PII
S30345278S0006302925060196-1
DOI
10.7868/S3034527825060196
Publication type
Article
Status
Published
Authors
Volume/ Edition
Volume 70 / Issue number 6
Pages
1221-1229
Abstract
One of the key challenges in transplantology is the limited period of safe, hypothermic storage for a donor heart. A promising solution to extend this time is gas hypothermic preservation using mixtures of oxygen and carbon monoxide, or other gas agents. However, standardizing this approach requires selecting the conditions for cardiac arrest and blood removal before gas exposure. The goal of this study was to investigate the feasibility of using hypobaric gas-hypothermic preservation for rat hearts, in combination with the cardioplegic solution Normacor mixed with the plasma substitute Gelofusin. An experimental study was conducted on isolated rat hearts ( = 30). Functional (contractility, heart rate) and morphological parameters were evaluated after 12 and 24 hours of storage at 4°C and 6.5 atm pressure of a CO : O (1 : 1) gas mixture. Three preparation protocols were compared: perfusion with "Normacor + Gelofusin" solution at 37°C, perfusion with Custodiol solution at 4°C, and storage without perfusion. It was shown that the "Normacor + Gelofusin" combination ensures stable recovery of cardiac contractile function (~50% of native control) and morphological integrity after 12 and 24 hours. After 12 hours, the Normacor group demonstrated a statistically significant improvement in functional recovery compared to the Custodiol group. Histological analysis revealed moderate, potentially reversible ischemia-reperfusion injuries in all groups after 24 hours of exposure to a gaseous medium. The combination of Normacor and Gelofusin solutions, both allowed for clinical use in Russia, was found to be an effective means for pre-conservative preparation of organs for subsequent gas-hypothermic preservation. This finding suggests that this approach could be introduced into clinical practice to extend the preservation time of donor hearts.
Keywords
нормакор кустодиол консервирующий раствор монооксид углерода хранение сердце трансплантология холодовая консервация
Date of publication
15.10.2025
Year of publication
2025
Number of purchasers
0
Views
39

References

  1. 1. Мультиорганное донорство для трансплантации. Руководство по хирургической технике эксплантации органов. Под ред. П. Асени, А. М. Гранде и Л. Де Карлиса (ГЭОТАР-Медиа, М., 2023).
  2. 2. Casanova D., Castillo F., and Minambres E. Multiorgan retrieval and preservation of the thoracic and abdominal organs in Maastricht III donors., World J Transplant., 12 (5), 83–87 (2022). DOI: 10.5500/wjt.v12.i5.83
  3. 3. Belzer F. O. and Southard J. H. Principles of solid-organ preservation by cold storage. Transplantation, 45 (4), 673–676 (1988). DOI: 10.1097/00007890-198804000-00001
  4. 4. Fernandez A. R., Sanchez-Tarjuelo R., Cravedi P., and Lopez-Hoyos M. Review: Ischemia reperfusion injury – A translational perspective in organ transplantation., Int. J. Mol. Sci., 21 (22), 8549 (2020). DOI: 10.3390/ijms21228549
  5. 5. Старикова Е. Г. Молекулярные механизмы действия газовых трансмиттеров при дизрегуляции апоптоза и пролиферации клеток линии Jurkat. Дис. … докт. мед. наук (14.03.03) (СибГМУ Минздрава России, Томск, 2014).
  6. 6. Nakao A., Choi A. M., and Murase N. Protective effect of carbon monoxide in transplantation. J. Cell. Mol. Med., 10 (3), 650–671 (2006). DOI: 10.1111/j.1582-4934.2006.tb00426.x
  7. 7. Hatayama N., Hirai S., Fukushige K., and Naito M. Different effects of partial pressure in a high-pressure gaseous mixture of carbon monoxide and oxygen for rat heart preservation., Sci Rep., 9 (1), 7480 (2019). DOI: 10.1038/s41598-019-43905-0
  8. 8. Фесенко (мл.) Е. Е., Гагаринский Е. Л., Аверин А. С. и Ковтун А. Л. Оценка сохранности миокарда крысы и изолированного сердца барана после пролонгированной 24-часовой гипотермической консервации под давлением газовой смеси на основе монооксида углерода, Биофизика, 65 (4), 780–791 (2020). DOI: 10.31857/S0006302920040213
  9. 9. Nakao A., Faleo G., Shimizu H., and Murase N. Ex vivo carbon monoxide prevents cytochrome P450 degradation and ischemia/reperfusion injury of kidney grafts., Kidney Int., 74 (8), 1009 (2008). DOI: 10.1038/ki.2008.342
  10. 10. Fujisaki N., Kohama K., Nishimura T., and Nakao A. Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats., Med. Gas. Res., 6 (3), 122–129 (2016). DOI: 10.4103/2045-9912.191357
  11. 11. Hatayama N., Hirai S., Fukushige K., and Naito M. Different effects of partial pressure in a high-pressure gaseous mixture of carbon monoxide and oxygen for rat heart preservation., Sci. Rep., 9 (1), 7480 (2019). DOI: 10.1038/s41598-019-43905-0
  12. 12. Suzuki C., Hatayama N., Ogawa T., and Hirai S. Cardioprotection via metabolism for rat heart preservation using the high-pressure gaseous mixture of carbon monoxide and oxygen., Int. J. Mol. Sci., 21 (22), 8858 (2020). DOI: 10.3390/ijms21228858
  13. 13. Овод А. И. и Новикова М. Д. Фармацевтический рынок кардиоплегических средств и особенности их применения в Российской Федерации, Мед.-фармацевтич. журн. «Пульс», 23 (9), 169–182 (2021). DOI: 10.26787/nydha-2686-6838-2021-23-9-169-182
  14. 14. Edelman J. J., Seco M., Dunne B., and Passage J. Custodiol for myocardial protection and preservation: a systematic review., Ann. Cardiothorac Surg., 2 (6), 717–728 (2013). DOI: 10.3978/j.issn.2225-319X.2013.11.10
  15. 15. Кустодиол – регистрационное удостоверение П N014656/01. Доступен по ссылке: https://www.rlsnet.ru/regdoc/kustodiol-p-n01465601-52408 (дата посещения 29.08.2025).
  16. 16. Гурин А. Е., Гагаринский Е. Л. и Фесенко Е. Е. (мл.) Влияние Кустодиола на сохранность изолированного сердца крысы при газовой гипотермической консервации под давлением смеси монооксида углерода и кислорода. Биофизика, 67 (5), 1002–1008 (2022). DOI: 10.31857/S0006302922050192
  17. 17. Schuerholz T., Weissig A., Juettner B., Becker T., and Scheinichen D. Ex vivo microvesicle formation after prolonged ischemia in renal transplantation, Thromb. Res., 120 (2), 231–236 (2007). DOI: 10.1016/j.thromres.2006.10.003
  18. 18. Баяндин Н. Л. Кристаллоидная гипотермическая и кровяная нормотермическая кардиоплегия. Клинич. и эксперимент. хирург. журн. им. акад. Б.В. Петровского, 8 (1), 80–89 (2020). DOI: 10.33029/2308-1198-2020- 8-1-80-89
  19. 19. Chernov I. I., Ivashchenko I. A., and Mandel I. A. The retrospective observational study of clinical outcomes of single dose infusion of warm blood cardioplegia in patients undergoing cardiac surgery, MedRxiv (2021). DOI: 10.1101/2021.07.15.21260424
  20. 20. Depre C., Vanoverschelde J. L. and Taegtmeyer H. Glucose for the heart. Circulation, 99 (4), 578–588 (1999) DOI: 10.1161/01.cir.99.4.578
  21. 21. Buja L. M. Pathobiology of Myocardial Ischemia and Reperfusion Injury: Models, modes, molecular mechanisms, modulation, and clinical applications. Cardiol. Rev., 31 (5), 252–264 (2023). DOI: 10.1097/CRD.0000000000000440
  22. 22. Кливер В. Е. Патоморфологический анализ трансплантированного сердца при различных сроках холодовой ишемии. Дис. … канд. мед. наук (3.3.2) (Новосибирский государственный медицинский университет, Новосибирск, 2024).
  23. 23. Ben Abdennebi H., Steghens J. P., Margonari J., Ramella-Virieux S., Barbieux A., and Boillot O. High-Na+ lowK+ UW cold storage solution reduces reperfusion injuries of the rat liver graft. Transpl. Int., 11 (3), 223–30 (1998). DOI: 10.1007/s001470050132
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