Vol. 28 No. 4 (2024)
EXPERIMENTAL STUDIES

Survival of the heart in different cardioplegic solution delivery systems under extracorporeal normothermic perfusion conditions: an experimental study

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  • S.D. Robustova,
  • V.S. Kachan,
  • D.V. Kononova,
  • A.S. Yarovoy,
  • M.A. Gusev,
  • V.V. Litvinenko,
  • V.D. Dzhabrailov,
  • A.A. Brichagina,
  • Z.V. Obrazumova,
  • S.D. Chekalina,
  • E.A. Turchaninova,
  • S.S. Bakumenko,
  • M.S. Nosov,
  • A.K. Berezhnoy,
  • V.A. Kozlov,
  • V.A. Tsvelaya,
  • K.I. Agladze
S.D. Robustova
Moscow Institute of Physics and Technology (National Research University), Moscow
Bio
V.S. Kachan
Moscow Institute of Physics and Technology (National Research University), Moscow
D.V. Kononova
Moscow Institute of Physics and Technology (National Research University), Moscow
A.S. Yarovoy
Moscow Institute of Physics and Technology (National Research University), Moscow
M.A. Gusev
Moscow Institute of Physics and Technology (National Research University), Moscow
V.V. Litvinenko
Moscow Institute of Physics and Technology (National Research University), Moscow
V.D. Dzhabrailov
Moscow Institute of Physics and Technology (National Research University), Moscow
A.A. Brichagina
Moscow Institute of Physics and Technology (National Research University), Moscow
Z.V. Obrazumova
Moscow Institute of Physics and Technology (National Research University), Moscow
S.D. Chekalina
Moscow Institute of Physics and Technology (National Research University), Moscow
E.A. Turchaninova
Moscow Institute of Physics and Technology (National Research University), Moscow
S.S. Bakumenko
Moscow Institute of Physics and Technology (National Research University), Moscow
M.S. Nosov
Moscow Institute of Physics and Technology (National Research University), Moscow; CardioSystemPharma, Khimki, Moscow Region
A.K. Berezhnoy
Moscow Institute of Physics and Technology (National Research University), Moscow; CardioSystemPharma, Khimki, Moscow Region
V.A. Kozlov
Moscow Institute of Physics and Technology (National Research University), Moscow; CardioSystemPharma, Khimki, Moscow Region
V.A. Tsvelaya
Moscow Institute of Physics and Technology (National Research University), Moscow; Moscow Regional Research and Clinical Institute, Moscow; ITMO University, Saint Petersburg
K.I. Agladze
Moscow Institute of Physics and Technology (National Research University), Moscow; Moscow Regional Research and Clinical Institute, Moscow
Изменение структуры кардиомиоцитов в срезе сердечной ткани, выявленное при иммуногистохимическом окрашивании после длительного сохранения
DOI: https://doi.org/10.21688/1681-3472-2024-4-78-93

Published 2024-12-27

Keywords

  • Cardioplegic Solutions,
  • Heart Arrest, Induced,
  • Heart Transplantation,
  • Ischemia,
  • NAD,
  • Perfusion,
  • Rats
    • ...More
    Less

How to Cite

Robustova, . S., Kachan, V., Kononova, D., Yarovoy, A., Gusev, M., Litvinenko, V., Dzhabrailov, V., Brichagina, A., Obrazumova, Z., Chekalina, S., Turchaninova, E., Bakumenko, S., Nosov, M., Berezhnoy, A., Kozlov, V., Tsvelaya, V., & Agladze, K. (2024). Survival of the heart in different cardioplegic solution delivery systems under extracorporeal normothermic perfusion conditions: an experimental study. Patologiya Krovoobrashcheniya I Kardiokhirurgiya, 28(4), 78–93. https://doi.org/10.21688/1681-3472-2024-4-78-93

Copyright (c) 2024 Robustova S.D., Kachan V.S., Kononova D.V., Yarovoy A.S., Gusev M.A., Litvinenko V.V., Dzhabrailov V.D., Brichagina A.A., Obrazumova Z.V., Chekalina S.D., Turchaninova E.A., Bakumenko S.S., Nosov M.S., Berezhnoy A.K., Kozlov V.A., Tsvelaya V.A., Agladze K.I.

Creative Commons License

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

Abstract

Introduction: Preservation of isolated hearts in cardioplegic solution at normothermia is a promising strategy for increasing the organ lifespan. Further development of this strategy and search for new products for solution delivery can help optimize the technology of donor heart transportation.
Objective: The study was aimed to test the efficacy of device for normothermic constant perfusion flow with innovative lines for the cardioplegic solution delivery (CardioSystemPharma, Khimki, Moscow Region, Russia) according to the Langendorff mode in comparison with a system based on nodes and tubes of Radnoti Langendorff Constant Perfusion Flow Apparatus (ADInstruments, Colorado Springs, USA) in a series of experiments on rat hearts.
Methods: The innovative cardioplegic delivery system (CardioSystemPharma) and traditional perfusion system (Radnoti) were compared in experiments on rat hearts at normothermia without cardioplegic solution and using the cardioplegic solution Normacor (Mosfarm, Moscow Region, Russia). The time until complete cardiac arrest and the changes in the NADH coenzyme fluorescence were recorded. After cardiac arrest, immunohistochemical staining of ventricular sections was performed to detect myocardial injury during perfusion.
Results: It was shown that the innovative cardioplegic delivery system was not inferior to the traditional perfusion system (Radnoti) and even surpassed it in terms of the time duration for preservation of the isolated heart. It was found that the using of elevated glucose concentration during normothermic perfusion could significantly increase the organ lifespan. The efficacy of normothermic perfusion in the experiment was confirmed by monitoring cellular respiration through recording the NADH fluorescence.
Conclusion: Testing showed that long-term preservation under normothermia with usage of an innovative delivery system of Russian manufacture is a promising replacement for Radnoti solution delivery system.

Received 16 October 2024. Revised 23 November 2024. Accepted 10 December 2024.

Funding
The study was carried out within the framework of the project “Innovative cardioplegic lines for cardiac surgery” under the Agreement on the provision of a grant from the Government of the Moscow Region in the fields of science, technology, engineering and innovation No. 12/04-24 dated 04/27/2024.

Conflict of interest
The authors declare no conflict of interest.

Contribution of the authors
Conception and study design: V.A. Tsvelaya, S.D. Robustova, V.S. Kachan, M.S. Nosov, A.K. Berezhnoy, V.A. Kozlov, K.I. Agladze
Data collection and analysis: S.D. Robustova, V.S. Kachan, D.V. Kononova, A.S. Yarovoy, M.A. Gusev, V.V. Litvinenko, V.D. Dzhabrailov, A.A. Brichagina, Z.V. Obrazumova, S.D. Chekalina, S.S. Bakumenko, E.A. Turchaninova, V.A. Tsvelaya
Statistic analysis: S.D. Robustova, V.S. Kachan, D.V. Kononova, A.S. Yarovoy, M.A. Gusev, V.V. Litvinenko, V.D. Dzhabrailov, A.A. Brichagina, Z.V. Obrazumova, S.D. Chekalina, S.S. Bakumenko, E.A. Turchaninova
Drafting the article: S.D. Robustova, V.S. Kachan, D.V. Kononova, Z.V. Obrazumova, E.A. Turchaninova, V.A. Tsvelaya
Critical revision of the article: S.D. Robustova, E.A. Turchaninova, V.A. Tsvelaya, K.I. Agladze
Final approval of the version to be published: S.D. Robustova, V.S. Kachan, D.V. Kononova, A.S. Yarovoy, M.A. Gusev, V.V. Litvinenko, V.D. Dzhabrailov, A.A. Brichagina, Z.V. Obrazumova, S.D. Chekalina, E.A. Turchaninova, S.S. Bakumenko, M.S. Nosov, A.K. Berezhnoy, V.A. Kozlov, V.A. Tsvelaya, K.I. Agladze

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References

  1. Beuth J., Falter F., Pinto Ribeiro R.V., Badiwala M., Meineri M. New strategies to expand and optimize heart donor pool: ex vivo heart perfusion and donation after circulatory death: a review of current research and future trends. Anesth Analg. 2019;128(3):406-413. PMID: 30531220. https://doi.org/10.1213/ANE.0000000000003919
  2. Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). OPTN/SRTR 2022 Annual Data Report. U.S. Department of Health and Human Services, Health Resources and Services Administration; 2024. Accessed 7.10.2024.
  3. Жульков М.О., Фомичев А.В., Альсов С.А., Кливер Е.Н., Чернявский А.М. Современное состояние проблемы и результаты ex vivo перфузии донорских сердец. Вестник трансплантологии и искусственных органов. 2019;21(4):143-146. https://doi.org/10.15825/1995-1191-2019-4-143-146 Zhulkov M.O., Fomichev A.V., Alsov S.A., Cleaver E.N., Chernyavsky A.M. Current state of the problem and results of ex vivo perfusion of donor hearts. Russian Journal of Transplantology and Artificial Organs. 2019;21(4):143-146. (In Russ.) https://doi.org/10.15825/1995-1191-2019-4-143-146
  4. McCartney S.L., Patel C., Del Rio J.M. Long-term outcomes and management of the heart transplant recipient. Best Pract Res Clin Anaesthesiol. 2017;31(2):237-248. PMID: 29110796. https://doi.org/10.1016/j.bpa.2017.06.003
  5. Preusse C.J. Custodiol cardioplegia: a single-dose hyperpolarizing solution. J Extra Corpor Technol. 2016;48(2):P15-P20.
  6. Jia S., Caranasos T.G., Kumar P.A. Pro: advantages of using TransMedics Organ Care System Heart in heart transplantation. J Cardiothorac Vasc Anesth. 2024;38(2):569-572. PMID: 38042742. https://doi.org/10.1053/j.jvca.2023.11.005
  7. Pinnelas R., Kobashigawa J.A. Ex vivo normothermic perfusion in heart transplantation: a review of the TransMedics® Organ Care System. Future Cardiol. 2022;18(1):5-15. PMID: 34503344. https://doi.org/10.2217/fca-2021-0030
  8. Волков И.М., Майдан В.А., Бокарев М.А. Факторы риска при пересадке сердца. Университетский терапевтический вестник. 2024;5(4):168-176. https://doi.org/10.56871/UTJ.2023.57.96.015 Volkov I.M., Maidan V.A., Bokarev M.A. Risk factors for heart transplantation. University Therapeutic Journal. 2024;5(4):168-176. (In Russ.) https://doi.org/10.56871/UTJ.2023.57.96.015
  9. Торопова Я.Г., Осяев Н.Ю., Мухамадияров Р.А. Перфузия изолированного сердца методами Лангендорфа и Нилли: особенности техники и применение в современных исследованиях. Трансляционная медицина. 2014;(4):34-39. https://doi.org/10.18705/2311-4495-2014-0-4-34-39 Toropova Ya.G., Osyaev N.Y., Mukhamadiyarov R.A. Perfusion of the isolated heart by Langendorff and Neely methods: particular techniques and applications in recent scientific research. Translational Medicine. 2014;(4):34-39. (In Russ.) https://doi.org/10.18705/2311-4495-2014-0-4-34-39
  10. King D.R., Hardin K.M., Hoeker G.S., Poelzing S. Reevaluating methods reporting practices to improve reproducibility: an analysis of methodological rigor for the Langendorff whole heart technique. Am J Physiol Heart Circ Physiol. 2022;323(3):H363-H377. PMID: 35749719; PMCID: PMC9359653. https://doi.org/10.1152/ajpheart.00164.2022
  11. Asfour H., Wengrowski A.M., Jaimes R. 3rd, Swift L.M., Kay M.W. NADH fluorescence imaging of isolated biventricular working rabbit hearts. J Vis Exp. 2012;(65):4115. PMID: 22872126; PMCID: PMC3476403. https://doi.org/10.3791/4115
  12. Bigio I.J., Mourant J.R. Optical biopsy. In: Encyclopedia of Optical Engineering. London: Taylor & Francis, 2003. P. 1577-1593.
  13. Салмин В.В., Салмина А.Б., Фурсов А.А., Фролова О.В., Лалетин Д.И., Фурсов М.А., Юдин Г.В., Малиновская Н.А., Зыкова Л.Д., Проворов А.С. Использование флуоресцентной спектроскопии для оценки ишемического повреждения миокарда. Журнал Сибирского федерального университета. Серия: Биология. 2011;4(2):142-157. Salmin V.V., Salmina A.B., Fursov A.A., Frolova O.V., Lale­tin D.I., Fursov M.A., Yudin G.V., Malinovskaya N.A., Zykova L.D., Provorov A.S. Application of fluorescence spectroscopy for assesment of myocardial ischemic injury. Journal of Siberian Federal University. Biology. 2011;4(2):142-157. (In Russ.)
  14. Papayan G., Petrishchev N., Galagudza M. Autofluorescence spectroscopy for NADH and flavoproteins redox state monitoring in the isolated rat heart subjected to ischemia-reperfusion. Photodiagnosis Photodyn Ther. 2014;11(3):400-408. PMID: 24854770. https://doi.org/10.1016/j.pdpdt.2014.05.003
  15. Wengrowski A.M., Kuzmiak-Glancy S., Jaimes R. 3rd, Kay M.W. NADH changes during hypoxia, ischemia, and increased work differ between isolated heart preparations. Am J Physiol Heart Circ Physiol. 2014;306(4):H529-H537. PMID: 24337462; PMCID: PMC3920244. https://doi.org/10.1152/ajpheart.00696.2013
  16. Chen X., Su Y., Reay D., Riffat S. Recent research developments in polymer heat exchangers — a review. Renewable and Sustainable Energy Reviews. 2016;60:1367-1386. https://doi.org/10.1016/j.rser.2016.03.024
  17. Фесенко Е.Е. мл., Гагаринский Е.Л., Аверин А.С., Грудинин Н.В., Гурин А.Е., Шишова Н.В., Швирст Н.Э., Гольтяев М.В., 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. 2020;65(4):780-791. https://doi.org/10.31857/S0006302920040213 Fesenko E.Е. Jr., Gagarinsky E.L., Averin A.S., Grudinin N.V., Gurin A.E., Shishova N.V., Shvirst N.E., Goltyaev M.V., Kovtun A.L. Evaluation of preservation of rat myocardium and isolated sheep heart following prolonged (24 hour) hypothermic preservation after exposure to a gaseous mixture composed of carbon monoxide and oxygen. Biophysics. 2020;65(4):780-791. (In Russ.) https://doi.org/10.31857/S0006302920040213
  18. Минасян С.М., Галагудза М.М., Сонин Д.Л., Боброва Е.А., Зверев Д.А., Королев Д.В., Дмитриев Ю.В., Васильева М.С., Григорова Ю.Н., Власов Т.Д. Методика перфузии изолированного сердца крысы. Регионарное кровообращение и микро­циркуляция. 2010;8(4):54-59. Minasian S.M., Galagudza М.М., Sonin D.L., Bobrova E.A., Zverev D.A., Korolev D.V., Dmitriev Yu.V., Vasilieva М.S., Grigorova Yu.N., Vlasov T.D. The technique of isolated rat heart perfusion. Regional Blood Circulation and Microcirculation. 2010;8(4):54-59. (In Russ.)