vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2023-3-122-128vtio-1649Research ArticleДонорство органовOrgan DonationХирургическая техника эксплантации работающего сердечно-легочного комплекса в экспериментеSurgical technique for explantation of a functioning cardiopulmonary complex in an experimentЖульковМ. О.ZhulkovM. O.

Новосибирск

Novosibirsk

medicus-maligna@mail.ruЗыковИ. С.ZykovI. S.

Новосибирск

Novosibirsk

i_zykov@meshalkin.ruМакаевА. Г.MakaevA. G.

Макаев Александр Геннадьевич,

630055, Новосибирск, ул. Речкуновская, д. 15

Alexander Makaev,

15, Rechkunovskaya str., Novosibirsk, 630055

makaev_a@meshalkin.ruПротопоповА. В.ProtopopovA. V.

Новосибирск

Novosibirsk

andrew-uss@yandex.ruМуртазалиевМ. Н.MurtazalievM. N.

Новосибирск

Novosibirsk

murtazaliev_m@meshalkin.ruКосимовФ. Ю.KosimovF. Yu.

Новосибирск

Novosibirsk

Kosimov-us@mail.ruТарковаА. Р.TarkovaA. R.

Новосибирск

Novosibirsk

a_tarkova@meshalkin.ruЛиманскийА. Д.LimanskyA. D.

Новосибирск

Novosibirsk

a.limanskii@g.nsu.ruСмирновЯ. М.SmirnovYa. M.

Новосибирск

Novosibirsk

sashamakaev@mail.ruАгаеваХ. А.AgaevaH. A.

Новосибирск

Novosibirsk

agaeva_k@meshalkin.ruФрыкинаО. Е.FrykinaO. E.

Новосибирск

Novosibirsk

frykina_o@meshalkin.ruСиротаД. А.SirotaD. A.

Новосибирск

Novosibirsk

d_sirota@meshalkin.ruФГБУ «Национальный медицинский исследовательский центр имени академика Е.Н. Мешалкина» Минздрава РоссииРоссияMeshalkin National Medical Research CenterRussian FederationНовосибирский государственный медицинский университетРоссияNovosibirsk State Medical UniversityRussian FederationИнститут медицины и психологии В. Зельмана Новосибирского государственного университетаРоссияZelman Institute of Medicine and Psychology, Novosibirsk State UniversityRussian Federation202317072023253122128Copyright © Жульков М.О., Зыков И.С., Макаев А.Г., Протопопов А.В., Муртазалиев М.Н., Косимов Ф.Ю., Таркова А.Р., Лиманский А.Д., Смирнов Я.М., Агаева Х.А., Фрыкина О.Е., Сирота Д.А., 20232023Жульков М.О., Зыков И.С., Макаев А.Г., Протопопов А.В., Муртазалиев М.Н., Косимов Ф.Ю., Таркова А.Р., Лиманский А.Д., Смирнов Я.М., Агаева Х.А., Фрыкина О.Е., Сирота Д.А.Zhulkov M.O., Zykov I.S., Makaev A.G., Protopopov A.V., Murtazaliev M.N., Kosimov F.Y., Tarkova A.R., Limansky A.D., Smirnov Y.M., Agaeva H.A., Frykina O.E., Sirota D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1649Цель

Цель: разработать и апробировать хирургическую технику эксплантации работающего сердечно-легочного комплекса в условиях нормотермической аутоперфузии.

Материалы и методы

Материалы и методы. В качестве экспериментальной модели для проведения серии острых экспериментов (n = 10) были использованы свиньи породы ландрас. Во время эксперимента проводили мониторинг инвазивного давления в полостях сердца и магистральных артериях, газового состава крови, сократительной способности миокарда. Эксплантацию работающего сердечно-легочного комплекса проводили через срединную стернотомию. Кондиционирование эксплантированного комплекса выполняли при 37–38 °С в течение 6 часов.

Результаты

Результаты. В ходе проведенной серии экспериментов была доказана принципиальная возможность стабильной работы изолированного комплекса «сердце – легкие» ex vivo на протяжении 6 часов при условии поддержания параметров базовых констант гомеостаза. Использованные технологические решения позволили обеспечить безопасную гемодинамическую и анатомическую изоляцию работающего сердечно-легочного комплекса.

Заключение

Заключение. Разработанный протокол изоляции работающего сердечно-легочного комплекса позволяет обеспечить стабильную функцию трансплантата на протяжении 6 часов в условиях нормотермической аутоперфузии. Реализация данной концепции при разработке транспортных систем позволит значительно облегчить их конструкцию и отказаться от использования дорогостоящих комплектующих, что будет способствовать широкому внедрению в клиническую практику.

Objective

Objective: to develop and approve the surgical technique for explantation of a functioning cardiopulmonary complex under normothermic autoperfusion.

Materials and methods

Materials and methods. Landrace pigs were used as the experimental model for a series of acute experiments (n = 10). During the experiment, invasive pressure in the cavities of the heart and main arteries, blood gas composition, and myocardial contractility were monitored. The functioning cardiopulmonary complex was explanted through a median sternotomy. The explanted complex was conditioned at 37–38 °C for 6 hours.

Results

Results. In the course of a series of experiments, it was shown that stable operation of the isolated heart-lung complex ex vivo for 6 hours was fundamentally possible provided that the parameters of the basic homeostasis constants are maintained. The technological solutions used made it possible to ensure safe hemodynamic and anatomical isolation of the working cardiopulmonary complex.

Conclusion

Conclusion. The developed protocol for isolating a functioning cardiopulmonary complex allows to provide stable graft function for 6 hours under normothermic autoperfusion. Implementation of this concept in the development of transport systems would significantly facilitate their design and eliminate the use of expensive components. This would contribute to widespread introduction into clinical practice.

хроническая сердечная недостаточностьпересадка сердцаконсервация сердцааутоперфузиясохранение донорских органовперфузия органов ex vivochronic heart failureheart transplantationheart preservationautoperfusiondonor organ preservationex vivo organ perfusionИсследование выполнено в рамках проекта № 23-25-10013 (Соглашение № 23-25-10013 от 20.04.2023 г. с РНФ, Соглашение № р-52 от 03.04.2023 г. с Министерством науки и инновационной политики НСО).ReferencesFomichev AV, Poptsov VN, Sirota DA, Zhulkov MO, Edemskiy AG, Protopopov АV et al. Mid-term and longterm outcomes following heart transplantation with prolonged cold ischemia. Russian Journal of Transplantology and Artificial Organs. 2023; 25 (1): 99–105. (In Russ.). https://doi.org/10.15825/1995-1191-2023-1-99-105.Fomichev AV, Poptsov VN, Sirota DA, Zhulkov MO, Edemskiy AG, Protopopov АV et al. Mid-term and longterm outcomes following heart transplantation with prolonged cold ischemia. Russian Journal of Transplantology and Artificial Organs. 2023; 25 (1): 99–105. (In Russ.). https://doi.org/10.15825/1995-1191-2023-1-99-105.Pannekoek A, Ali U. Does the solution used for cold static storage of hearts impact on heart transplant survival? Interact Cardiovasc Thorac Surg. 2021; 33 (5): 814–818. doi: 10.1093/icvts/ivab164.Pannekoek A, Ali U. Does the solution used for cold static storage of hearts impact on heart transplant survival? Interact Cardiovasc Thorac Surg. 2021; 33 (5): 814–818. doi: 10.1093/icvts/ivab164.Fomichev AV, Khvan DS, Agaeva HA, Zhulkov MO, Doronin DV, Chernyavsky AM. Experience of heart transplantation with an extended cold ischemic time of donor heart. Russian Journal of Cardiology. 2020; 25 (8): 4011. https://doi.org/10.15829/1560-4071-2020-4011.Fomichev AV, Khvan DS, Agaeva HA, Zhulkov MO, Doronin DV, Chernyavsky AM. Experience of heart transplantation with an extended cold ischemic time of donor heart. Russian Journal of Cardiology. 2020; 25 (8): 4011. https://doi.org/10.15829/1560-4071-2020-4011.Qin G, Jernryd V, Sjöberg T, Steen S, Nilsson J. Machine Perfusion for Human Heart Preservation: A Systematic Review. Transpl Int. 2022; 35: 10258. doi: 10.3389/ti.2022.10258.Qin G, Jernryd V, Sjöberg T, Steen S, Nilsson J. Machine Perfusion for Human Heart Preservation: A Systematic Review. Transpl Int. 2022; 35: 10258. doi: 10.3389/ti.2022.10258.Peters-Sengers H, Houtzager JHE, Idu MM, Heemskerk MBA, van Heurn ELW, Homan van der Heide JJ et al. Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry. Transplant Direct. 2019; 5 (5): e448. doi: 10.1097/TXD.0000000000000888.Peters-Sengers H, Houtzager JHE, Idu MM, Heemskerk MBA, van Heurn ELW, Homan van der Heide JJ et al. Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry. Transplant Direct. 2019; 5 (5): e448. doi: 10.1097/TXD.0000000000000888.Ontario Health (Quality). Portable Normothermic Cardiac Perfusion System in Donation After Cardiocirculatory Death: A Health Technology Assessment. Ont Health Technol Assess Ser. 2020; 20 (3): 1–90.Ontario Health (Quality). Portable Normothermic Cardiac Perfusion System in Donation After Cardiocirculatory Death: A Health Technology Assessment. Ont Health Technol Assess Ser. 2020; 20 (3): 1–90.Van Raemdonck D, Rega F, Rex S, Neyrinck A. Machine perfusion of thoracic organs. J Thorac Dis. 2018; 10 (Suppl 8): S910–S923. doi: 10.21037/jtd.2018.02.85.Van Raemdonck D, Rega F, Rex S, Neyrinck A. Machine perfusion of thoracic organs. J Thorac Dis. 2018; 10 (Suppl 8): S910–S923. doi: 10.21037/jtd.2018.02.85.Zhulkov MO, Sirota DA, Zykov IS, Sabetov AK, Agaeva KA, Makaev АG et al. Results of a study of the effectiveness of direct coronary oxygen persufflation as a donor heart conditioning method. Russian Journal of Transplantology and Artificial Organs. 2022; 24 (3): 111–120. https://doi.org/10.15825/1995-1191-2022-3-111-120.Zhulkov MO, Sirota DA, Zykov IS, Sabetov AK, Agaeva KA, Makaev АG et al. Results of a study of the effectiveness of direct coronary oxygen persufflation as a donor heart conditioning method. Russian Journal of Transplantology and Artificial Organs. 2022; 24 (3): 111–120. https://doi.org/10.15825/1995-1191-2022-3-111-120.Pinnelas R, Kobashigawa JA. Ex vivo normothermic perfusion in heart transplantation: a review of the TransMedics® Organ Care System. Future Cardiol. 2022; 18 (1): 5–15. doi: 10.2217/fca-2021-0030.Pinnelas R, Kobashigawa JA. Ex vivo normothermic perfusion in heart transplantation: a review of the TransMedics® Organ Care System. Future Cardiol. 2022; 18 (1): 5–15. doi: 10.2217/fca-2021-0030.Slama A, Schillab L, Barta M, Benedek A, Mitterbauer A, Hoetzenecker K et al. Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial. J Heart Lung Transplant. 2017; 36 (7): 744–753. doi: 10.1016/j.healun.2017.02.011.Slama A, Schillab L, Barta M, Benedek A, Mitterbauer A, Hoetzenecker K et al. Standard donor lung procurement with normothermic ex vivo lung perfusion: A prospective randomized clinical trial. J Heart Lung Transplant. 2017; 36 (7): 744–753. doi: 10.1016/j.healun.2017.02.011.Jochmans I, O’Callaghan JM, Pirenne J, Ploeg RJ. Hypothermic machine perfusion of kidneys retrieved from standard and high-risk donors. Transpl Int. 2015; 28 (6): 665–676. doi: 10.1111/tri.12530.Jochmans I, O’Callaghan JM, Pirenne J, Ploeg RJ. Hypothermic machine perfusion of kidneys retrieved from standard and high-risk donors. Transpl Int. 2015; 28 (6): 665–676. doi: 10.1111/tri.12530.Pettit SJ, Petrie MC. Transplantation of Hearts Donated After Circulatory-Determined Death. Circ Heart Fail. 2019; 12 (4): e005991. doi: 10.1161/CIRCHEARTFAILURE.119.005991.Pettit SJ, Petrie MC. Transplantation of Hearts Donated After Circulatory-Determined Death. Circ Heart Fail. 2019; 12 (4): e005991. doi: 10.1161/CIRCHEARTFAILURE.119.005991.Zhulkov MO, Fomichev AV, Alsov SA, Cleaver EN, Chernyavsky AM. 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. https://doi.org/10.15825/1995-1191-2019-4- 143-146.Zhulkov MO, Fomichev AV, Alsov SA, Cleaver EN, Chernyavsky AM. 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. https://doi.org/10.15825/1995-1191-2019-4- 143-146.Starling EH, Visscher MB. The regulation of the energy output of the heart. J Physiol. 1927; 62 (3): 243–261. doi: 10.1113/jphysiol.1927.sp002355.Starling EH, Visscher MB. The regulation of the energy output of the heart. J Physiol. 1927; 62 (3): 243–261. doi: 10.1113/jphysiol.1927.sp002355.Zimmer HG. Modifications of the isolated frog heart preparation in Carl Ludwig’s Leipzig Physiological Institute: relevance for cardiovascular research. Can J Cardiol. 2000; 16 (1): 61–69.Zimmer HG. Modifications of the isolated frog heart preparation in Carl Ludwig’s Leipzig Physiological Institute: relevance for cardiovascular research. Can J Cardiol. 2000; 16 (1): 61–69.Zimmer HG. Who discovered the Frank-Starling mechanism? News Physiol Sci. 2002; 17: 181–184. doi: 10.1152/nips.01383.2002.Zimmer HG. Who discovered the Frank-Starling mechanism? News Physiol Sci. 2002; 17: 181–184. doi: 10.1152/nips.01383.2002.Fye WB. H. Newell Martin and the isolated heart preparation: the link between the frog and open heart surgery. Circulation. 1986; 73 (5): 857–864. doi: 10.1161/01.cir.73.5.857.Fye WB. H. Newell Martin and the isolated heart preparation: the link between the frog and open heart surgery. Circulation. 1986; 73 (5): 857–864. doi: 10.1161/01.cir.73.5.857.Elzinga G. Cross Talk Between Left and Right Heart: A Study on the Isolated Heart. Vrije Univ. te Amsterdam. 1972.Elzinga G. Cross Talk Between Left and Right Heart: A Study on the Isolated Heart. Vrije Univ. te Amsterdam. 1972.Patterson SW, Starling EH. The carbohydrate metabolism of the isolated heart lung preparation. J Physiol. 1913; 47 (1–2): 137–148. doi: 10.1113/jphysiol.1913.sp001617.Patterson SW, Starling EH. The carbohydrate metabolism of the isolated heart lung preparation. J Physiol. 1913; 47 (1–2): 137–148. doi: 10.1113/jphysiol.1913.sp001617.Patterson SW, Starling EH. On the mechanical factors which determine the output of the ventricles. J Physiol. 1914; 48 (5): 357–379. doi: 10.1113/jphysiol.1914. sp001669.Patterson SW, Starling EH. On the mechanical factors which determine the output of the ventricles. J Physiol. 1914; 48 (5): 357–379. doi: 10.1113/jphysiol.1914. sp001669.Langendorff O. Untersuchungen am überlebenden Säugethierherzen. Arch für die gesamte Physiol des Menschen und der Tiere. 1895; 61: 291–332.Langendorff O. Untersuchungen am überlebenden Säugethierherzen. Arch für die gesamte Physiol des Menschen und der Tiere. 1895; 61: 291–332.Neely JR, Liebermeister H, Battersby EJ, Morgan HE. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967; 212 (4): 804–814. doi: 10.1152/ajplegacy.1967.212.4.804.Neely JR, Liebermeister H, Battersby EJ, Morgan HE. Effect of pressure development on oxygen consumption by isolated rat heart. Am J Physiol. 1967; 212 (4): 804–814. doi: 10.1152/ajplegacy.1967.212.4.804.Simaan J, Fawaz G. The mechanical efficiency of the Starling heart-lung preparation. Pflugers Arch. 1968; 302 (2): 123–132. doi: 10.1007/BF00586865.Simaan J, Fawaz G. The mechanical efficiency of the Starling heart-lung preparation. Pflugers Arch. 1968; 302 (2): 123–132. doi: 10.1007/BF00586865.Huisman PH, Schipperheyn JJ. The isolated heart-lung preparation. The Hague: Martinus Nijhoff Medical Division, 1978. 36–36.Huisman PH, Schipperheyn JJ. The isolated heart-lung preparation. The Hague: Martinus Nijhoff Medical Division, 1978. 36–36.Langer RM. Vladimir P. Demikhov, a pioneer of organ transplantation. Transplant Proc. 2011; 43 (4): 1221– 1222. doi: 10.1016/j.transproceed.2011.03.070.Langer RM. Vladimir P. Demikhov, a pioneer of organ transplantation. Transplant Proc. 2011; 43 (4): 1221– 1222. doi: 10.1016/j.transproceed.2011.03.070.Kozlov IA, Krichevskiy LA. Heart Transplantation in the USSR and Former Soviet Countries. J Cardiothorac Vasc Anesth. 2020; 34 (12): 3398–3408. doi: 10.1053/j.jvca.2019.12.001.Kozlov IA, Krichevskiy LA. Heart Transplantation in the USSR and Former Soviet Countries. J Cardiothorac Vasc Anesth. 2020; 34 (12): 3398–3408. doi: 10.1053/j.jvca.2019.12.001.Zhulkov MO, Zykov IS, Sirota DA, Agaeva HA, Sabetov AK, Poveschenko OV et al. Long-Term Conditioning of a Donor Heart by Autoperfusion. Journal of experimental and clinical surgery. 2022; 15: 3: 214–220. doi: 10.18499/2070-478X-2022-15-3-214-220.Zhulkov MO, Zykov IS, Sirota DA, Agaeva HA, Sabetov AK, Poveschenko OV et al. Long-Term Conditioning of a Donor Heart by Autoperfusion. Journal of experimental and clinical surgery. 2022; 15: 3: 214–220. doi: 10.18499/2070-478X-2022-15-3-214-220.

The authors declare that there are no conflicts of interest present.