The shortage of organs for transplant remains a major challenge in transplantology. Transporting donor organs over long distances increases cold ischemia time, which is a risk factor for ischemia-reperfusion injury (IRI). In the face of critical shortages, the method and timing of organ preservation are crucial in increasing the donor pool. This paper examines the approaches, benefits, and drawbacks of organ preservation techniques used around the world.
Objective: to conduct a comparative study of the efficacy of Custodiol® cardioplegia (Custodiol HTK, Dr. Franz Köhler Chemie GmbH, Bensheim, Germany) and normothermic autoperfusion of heart graft as a part of an ex vivo cardiopulmonary complex (CPC). Methods. Landrace pigs weighing 50 ± 5 kg and aged 4–5 months (n = 10) were used as the model for a series of acute experiments. In the experimental group (n = 5), the CPC was conditioned by autoperfusion for 6 hours. In the control group, the heart’s pumping function was restored after a 6-hour cold preservation with Custodiol®. The effectiveness of cardiac graft preservation methods was evaluated by measuring myocardial ischemic markers, endothelial synthetic function, and endothelial cell activation markers (E- and P-selectins, endothelial growth factor).Results. Following cardiac graft reperfusion, the control group exhibited a statistically significant increase in the concentration of myocardial ischemia markers; also, there was a significant decrease in the synthesis of endothelium-derived relaxing factor in the Custodiol® solution preservation group (378.5 [226.4; 539.7] vs. 542.1 [377.6; 853.2] μM/mL in the autoperfusion group, p < 0.05). The degree of coronary endothelial reperfusion injury/activation was several times higher in the control group than in the normothermic autoperfusion conditioning group. Moreover, cardiac output after a 6-hour graft conditioning was 0.63 [0.37; 0.80] and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (p < 0.05).Conclusion. Normothermic autoperfusion showed a significant advantage in preserving the morphofunctional status of the donor heart compared with cold preservation with Custodiol® during 6 hours of ex vivo graft conditioning.
Objective : to develop and approve the surgical technique for explantation of a functioning cardiopulmonary complex under normothermic autoperfusion. 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 . 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 . 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.
Medical management of end-stage chronic heart failure (HF) has evolved significantly over the past few decades. With a better understanding of the pathophysiology of HF, new pharmacological agents have been synthesized. However, survival in this cohort of patients with medical treatment remains extremely low. This has stimulated the development of surgical methods of treatment. Recent technological advances in the development of mechanical circulatory assist devices have made possible a single-stage implantation of two centrifugal pumps as an alternative to a total artificial heart. Today ventricular assist devices can be implanted to provide both univentricular and biventricular support depending on the severity of hemodynamic disorders, target organ damage, likelihood of recovery and heart transplantation.
Objective: To compare the effectiveness of 6-hour normothermic autoperfusion of a heart graft ex vivo with pharmaco-cold preservation using Bretschneider's solution (Custodiol, Dr Franz Köhler Chemie GmbH, Bensheim, Germany).Methods: Landrace pigs weighing 50 ± 5 kg and aged 4–5 months (n = 10) were selected as a model for a series of acute experiments. Cardiopulmonary conditioning using autoperfusion was conducted for 6 hours on the experimental group (n = 5). On the other hand, the control group underwent a 6-hour pharmaco-cold preservation with Bretschneider solution to recover the heart's pumping function. Graft preservation effectiveness was evaluated by measuring hemodynamic parameters, heartbeat, and myocardial ischemia marker concentrations.Results: After reperfusion and isolation of the working cardiopulmonary complex, cardiac output was 0.63 [0.37; 0.8] L/min and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (P < .05). The levels of CPK-MB, LDH, troponin-I, and lactate in the coronary sinus blood was significantly higher in the control group.Conclusion: The study demonstrated significant benefits of normothermic autoperfusion in maintaining the morphofunctional status of the donor heart compared to pharmaco-cold preservation using Bretschneider's solution for 6 hours of ex vivo graft conditioning. Received 16 July 2023. Revised 8 September 2023. Accepted 11 September 2023. Funding: The study was carried out within the framework of project No. 23-25-10013 (agreement No. 23-25-10013 dated April 20, 2023 with the Russian Science Foundation, agreement No. р-52 dated April 3, 2023 with the Ministry of Science and Innovation Policy of the Novosibirsk Region). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, I.S. ZykovData collection and analysis: M.O. Zhulkov, A.R. Tarkova, I.S. Zykov, A.G. Makaev, A.V. Protopopov, M.N. Murtazaliev, F.Yu. Kosimov, N.A. Karmadonova, Ya.M. Smirnov, E.E. Kliver, A.M. Volkov, H.A. Agaeva, D.A. SirotaStatistical analysis: M.O. ZhulkovDrafting the article: M.O. ZhulkovCritical revision of the article: M.O. Zhulkov, D.A. Sirota, I.S. ZykovFinal approval of the version to be published: M.O. Zhulkov, A.R. Tarkova, I.S. Zykov, A.G. Makaev, A.V. Protopopov, M.N. Murtazaliev, F.Yu. Kosimov, N.A. Karmadonova, Ya.M. Smirnov, E.E. Kliver, A.M. Volkov, H.A. Agaeva, D.A. Sirota
Цель. Провести сравнительное исследование эффективности 6-часовой нормотермической аутоперфузии сердечного трансплантата ex vivo и фармакохолодовой консервации кустодиолом (Custodiol HTK, Dr Franz Köhler Chemie GmbH, Бенсхайм, Германия). Методы. В качестве модели для проведения серии острых экспериментов использовали свиней породы ландрас весом 50 ± 5 кг в возрасте 4–5 мес. (n = 10). В экспериментальной группе (n = 5) кондиционирование сердечно-легочного комплекса проводили методом аутоперфузии в течение 6 ч. В контрольной группе восстановление насосной функции сердца осуществляли после 6-часовой фармакохолодовой консервации кустодиолом. Оценивали эффективность консервации трансплантата путем измерения параметров гемодинамики, ударной работы сердца, концентрации маркеров ишемии миокарда. Результаты. После реперфузии и изоляции работающего сердечно-легочного комплекса сердечный выброс составил 0,63 [0,37; 0,80] и 0,37 [0,23; 0,37] л/мин в экспериментальной и контрольной группах соответственно (р < 0,05). Концентрация креатинфосфокиназы-МВ, лактатдегидрогеназы, тропонина I и лактата в оттекающей из коронарного синуса крови была в 2 раза выше в группе контроля. Заключение. Нормотермическая аутоперфузия показала значительное преимущество в сохранении морфофункционального статуса донорского сердца по сравнению с фармакохолодовой консервацией кустодиолом в течение 6 ч кондиционирования трансплантата ex vivo. Поступила в редакцию 16 июля 2023 г. Исправлена 8 сентября 2023 г. Принята к печати 11 сентября 2023 г. Финансирование Исследование выполнено в рамках проекта № 23-25-10013 (соглашение № 23-25-10013 от 20.04.2023 г. с Российским научным фондом, соглашение № р-52 от 03.04.2023 г. с Министерством науки и инновационной политики Новосибирской области). Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: М.О. Жульков, Д.А. Сирота, И.С. Зыков Сбор и анализ данных: все авторы Статистическая обработка данных: М.О. Жульков Написание статьи: М.О. Жульков Исправление статьи: М.О. Жульков, Д.А. Сирота, И.С. Зыков Утверждение окончательного варианта статьи: все авторы
Objective: to carry out a comparative study of the efficacy of a 6-hour normothermic ex vivo heart and lung autoperfusion and cold cardioplegia using Bretschneider’s solution (Custodiol ® , Germany). Materials and methods. Landrace pigs weighing 50 ± 5 kg at the age of 4–5 months (n = 10) were used as a model for a series of acute experiments. In the experimental group (n = 5), the cardiopulmonary complex was conditioned by autoperfusion for 6 hours. In the control group, the heart pumping function was restored after 6-hour cold cardioplegia using Bretschneider’s solution. The efficiency of graft preservation was assessed by measuring hemodynamic parameters, myocardial contractile function, and myocardial oxygen consumption. Results. After reperfusion and repeated isolation of the working cardiopulmonary complex, cardiac output was 0.63 [0.37; 0.8] L/min and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (p < 0.05). Indicators – global left ventricular stroke work index and preload recruitable stroke work – were significantly higher in the experimental group (p < 0.05). Conclusion. Normothermic autoperfusion is significantly more effective in preserving the morphofunctional status of a donor heart than static cold storage with Bretschneider solution for 6 hours.
The aim of research was to study parameters of homeostasis and conditions for stable operation of the autoperfused heart-lung complex ex vivo.Materials and methods. A series of acute experiments (n-3) was carried out to create a functioning heart-lung complex and study parameters of homeostasis ex vivo. A large mammal (mini-pig weighed 20-30 kg) was used as an experimental model. During the experiment, invasive blood pressure in the aortic root, pulmonary artery, central venous pressure, temperature of the left ventricle of the heart, gas composition of arterial blood (in the aortic root) and venous blood flowing from the coronary sinus was monitored.Results. The series of experiments evidenced the fundamental possibility of an isolated heart-lung complex ex vivo stable functioning. During 4-hours autoperfusion of the "heart-lung" complex, the parameters of hemodynamics, gas and biochemical blood composition remained within the reference values.Conclusion. The analysis of literature data and the results of experiments on laboratory animals allow us to state that the autoperfusion can be successfully used as an option of safe and long-term conditioning of a donor heart. This technique can be used to improve the results of heart transplantation with prolonged ischemia of the donor organ. Extending the survival of a donor heart ex vivo functioning will significantly expand the geography of donor bases, reducing the ischemic period to a minimum.
Objective: To evaluate the performance and short-term capacity of the diepoxy-treated bovine jugular vein conduit in large animals during 6-month follow-up.Methods: Thirteen diepoxy-treated bovine jugular vein conduits were implanted into the pulmonary artery of young mini-pigs. During the follow-up, graft function was tested using transesophageal echocardiography. The animals were withdrawn at 6 months, and the explanted conduits were assessed histologically.Results: All the conduits were successfully implanted without any surgical complications. All the animals survived throughout the follow-up. By the end of the follow-up period, the pressure gradient increased on five animals’ conduits including one case of mismatch between the conduit and the native pulmonary artery, two cases of distal stenosis, and two case of endocarditis. No significant increase in valve regurgitation or conduit thrombosis was observed during the follow-up. In conduits without dysfunction, the structure of the walls and leaflets was intact. A thin fibrous tissue covered the conduit inner wall with complete surface endothelialization. Neither signs of degeneration or calcification nor inflammatory cells were found in the conduit wall or leaflets. Neointima proliferation without calcium deposits was observed in two distally stenosed conduits. Inflammatory cells consisting of multinucleated macrophages, lymphocytes, and histiocytes were found in the adventitia. There were no inflammatory cells in the media or intima, and the leaflets showed no changes.Conclusion: Diepoxy-treated bovine jugular vein demonstrated acceptable performance, good endothelialization, and low tendency to thrombosis and calcium accumulation in the wall and leaflets. Received 31 October 2022. Revised 25 November 2022. Accepted 28 November 2022. Funding: The study was supported by Russian Science Foundation (grant No. 22-25-20102). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: N.R. Nichay, I.Yu. Zhuravleva, A.V. Bogachev-ProkophievData collection and analysis: N.R. Nichay, Yu.Yu. Kulyabin, I.S. Zykov, E.V. Boyarkin, O.Yu. Malakhova, E.V. Kuznetsova, T.P. Timchenko, Ya.L. Rusakova, I.S. Murashov, A.A. DokuchaevaStatistical analysis: N.R. Nichay, I.Yu. ZhuravlevaDrafting the article: N.R. Nichay, I.Yu. Zhuravleva, Yu.Yu. Kulyabin, I.S. Zykov, E.V. Boyarkin, O.Yu. Malakhova, T.P. Timchenko, Ya.L. Rusakova, I.S. Murashov, A.A. DokuchaevaCritical revision of the article: N.R. Nichay, I.Yu. Zhuravleva, Yu.Yu. Kulyabin, A.A. Dokuchaeva, A.V. Bogachev-ProkophievFinal approval of the version to be published: N.R. Nichay, I.Yu. Zhuravleva, Yu.Yu. Kulyabin, I.S. Zykov, E.V. Boyarkin, O.Yu. Malakhova, E.V. Kuznetsova, T.P. Timchenko, Ya.L. Rusakova, I.S. Murashov, A.A. Dokuchaeva, A.V. Bogachev-Prokophiev
Цель. Оценить влияние внутрикоронарного введения иопромида (Ultravist®, Bayer AG, Леверкузен, Германия) в период реализации фармакохолодовой консервации донорского сердца ex vivo на восстановление насосной функции сердца и метаболизм кардиомиоцитов в раннем посттрансплантационном периоде. Методы. В качестве экспериментальной модели использовали телят черно-пестрой породы в возрасте 3 мес. В контрольной группе фармакохолодовую консервацию донорского сердца выполняли введением в корень аорты 2 л раствора кустодиола (Custodiol®, Dr. Franz Köhler Chemie GmbH, Бенсхайм, Германия). Затем сердца хранили в соответствующем растворе при температуре от 0 до 1 °C в течение 2 ч. Спустя 120 мин консервации в экспериментальной группе (n = 6) в корень аорты вводили раствор иопромида (Ultravist®) и кустодиола в соотношении 50:50 в течение 5 мин под давлением 70–80 мм рт. ст., после чего отмывали коронарное русло 1 л раствора кустодиола под давлением 40 мм рт. ст. и выполняли ортотопическую трансплантацию сердца реципиенту. В посттрансплантационном периоде исследовали параметры центральной гемодинамики, потребления миокардом кислорода, уровень маркеров ишемии миокарда (тропонина-I, креатинфосфокиназы-МВ, лактатдегидрогеназы). Результаты. В ходе исследования выполнили 12 ортотопических трансплантаций сердца. Через 120 мин после восстановления самостоятельной сердечной деятельности уровень сердечного выброса составил 5,11 [4,99; 5,41] и 5,77 [4,97; 6,62] л/мин (р = 0,0009) в контрольной и экспериментальной группах соответственно. Изменения концентрации лактатдегидрогеназы, тропонина-I и лактата в оттекающей из коронарного синуса крови были значительно более выраженными в раннем реперфузионном периоде, однако статистически значимого различия между группами не выявили (р > 0,05). Потребление миокардом кислорода было значительно снижено на этапе реперфузии, однако к 60-й минуте реперфузии возвращалось к исходным значениям без достоверной разницы между группами (р > 0,05). Заключение. В ходе эксперимента доказана безопасность внутрикоронарного введения иопромида на этапе фармакохолодовой консервации донорского сердца ex vivo. Внутрикоронарное введение раствора иопромида не влияет на восстановление насосной функции сердца и метаболизма кардиомиоцитов в раннем посттрансплантационном периоде. Поступила в редакцию 6 мая 2022 г. Исправлена 14 июня 2022 г. Принята к печати 11 июля 2022 г. Финансирование Исследование не имело спонсорской поддержки. Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: М.О. Жульков, Д.А. Сирота, И.С. Зыков Сбор и анализ данных: М.О. Жульков, И.С. Зыков, А.К. Сабетов, Х.А. Агаева, А.Г. Макаев, Д.М. Осинцев, А.Э. Календарев, А.П. Надеев, В.Е. Кливер, А.Р. Таркова, М.А. Овчинникова, Н.А. Кармадонова, Д.В. Хомушку Статистическая обработка данных: М.О. Жульков, А.Г. Макаев Написание статьи: М.О. Жульков Исправление статьи: М.О. Жульков, Д.А. Сирота, И.С. Зыков, А.В. Фомичев Утверждение окончательного варианта статьи: все авторы
Objective: to evaluate the technical feasibility as well as functional, metabolic and structural integrity of donor heart myocardium after 4 hours of direct intracoronary oxygen persufflation in an experiment. Materials and methods. Mini-pig siblings aged 3 months with a body weight of 23–36 kg were used as the experimental model. In the control group (n = 8), donor hearts were cold preserved by injecting 2 liters of Bretschneider cardioplegic solution (Custodiol®, Germany, HTK) into the aortic root. In the experimental group (n = 8), modified HTK solution (with 40 mg/L hyaluronidase added) was used to initiate cardioplegia, then moistened carbogen (95% O2, 5% CO2) was injected into the ascending aorta, maintaining 40–45 mm Hg aortic root pressure. The hearts were stored in an mHTK solution at 0–4 °С. After 3 hours of donor heart preservation, orthotopic heart transplantation (OHTx) was performed. In the post-transplant period, we studied central hemodynamic parameters, myocardial oxygen consumption, level of myocardial ischemia markers (troponin I, TnI; creatine phosphokinase-MB, CPKMB; lactate dehydrogenase, LDH), and histological signs of structural cellular injury. Results. Sixteen OHTx surgeries were performed during the study. At 120 minutes after restoration of spontaneous cardiac activity, cardiac output was 2.99 [4.85; 3.17] L/min and 2.48 [2.04; 2.92] L/min (p > 0.05) in the control and experimental groups, respectively. Changes in LDH, TnI and lactate levels in the blood flowing from the coronary sinus were significantly higher in the early reperfusion period. However, there was no statistically significant difference between the groups (p > 0.05). Myocardial oxygen consumption in the control and experimental groups was 8.2 [7.35; 9.35] ml-O2/min/100 g and 7.7 [6.75; 10.12] ml-O2/min/100 g, respectively (p > 0.05). Morphological examinations also showed no significant myocardial ischemia injury in the persufflation group compared to the control group. Conclusion. The experiment showed the technical feasibility and safety of direct intracoronary oxygen persufflation for 4 hours at the ex vivo donor heart conditioning stage. At the same time, experimental data showed no significant advantages of coronary persufflation over the standard protocol of cold preservation of donor heart with Bretschneider cardioplegic solution.
Background. In recent years, transcatheter implantation of the aortic valve has become increasingly performed as an alternative to "open" prosthetics. The undoubted advantage of this technology is its minimally invasive nature, which in most cases provides a favorable clinical outcome of the intervention. The transcatheter method of aortic valve prosthetics does not require sternotomy and connection of an artificial circulation device, which significantly reduces the risk of postoperative mortality and complications. However, despite all the advantages of the existing models, they are not without drawbacks that force researchers to develop and test new transcatheter valves. The problem of experimental studies of new models of self-opening transcatheter aortic valves is mainly determined by the anatomical features of the aortic root of animals. In this regard, the development of a reliable method of implantation of valve prostheses in the experiment is an urgent problem of preclinical testing.Aim. Development of a protocol for open implantation of a transcatheter aortic valve in experiment and evaluation of long-term results.Methods. To develop an experimental model, pigs of the "Landras" breed, females weighing 129.83 ± 9 kg were used. Transcatheter aortic valve implantation was performed under conditions of artificial circulation and moderate hypothermia (33-34°C) through a transverse aortotomy under the control of vision. During the experiment, invasive monitoring of blood pressure, central venous pressure, heart rhythm, body temperature, blood gas composition, activated clotting time was performed. The correct positioning and hemodynamic parameters after implantation were evaluated using transesophageal echocardiography.Results. In a series of chronic experiments, 18 open implantations of self-opening transcatheter aortic valves were performed. Successful positioning was achieved in 100% of cases. The developed protocol of open implantation made it possible to achieve reliable fixation of the prosthesis in the orthotopic position, as well as to prevent the migration of the prosthesis, the development of mitral regurgitation, paraaortic fistulas and coronary circulation disorders.Conclusion. In the course of the study, a simple and effective method of open implantation of a transcatheter aortic heart valve prosthesis was developed in an experiment. Received 1 October 2021. Revised 1 November 2021. Accepted 12 November 2021. Funding: This work was carried out within the framework of the state task of Ministry of Health of Russian Federation No. 121032300337-5. Conflict of interest: Authors declare no conflict of interest. Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, K.V. Kozyr, D.S. SergeevichevData collection and analysis: M.O. ZhulkovDrafting the article: M.O. ZhulkovCritical revision of the article: D.A. Sirota, A.M. ChernyavskiyExperimental part: M.O. Zhulkov, H.A. Agaeva, A.K. Sabetov, I.S. Zykov, A.R. TarkovaFinal approval of the version to be published: M.O. Zhulkov, K.V. Kozyr, I.S. Zykov, A.R. Tarkova, H.A. Agaeva, A.K. Sabetov, D.A. Sirota, D.S. Sergeevichev, A.M. Chernyavski
Objective: To evaluate the effect of intracoronary iopromide (Ultravist®, Bayer, AG, Leverkusen, Germany) during pharmaco-cold ex vivo preservation of a donor heart on the restoration of heart pumping function and cardiomyocyte metabolism in the early post-transplant period.Methods: Black-and-white calves aged 3 months were used as an experimental model. In the control group, pharmaco-cold preservation of the donor heart was performed by injecting 2 liters of custodiol (Custodiol®, Dr. Franz Köhler Chemie GmbH, Bensheim, Germany) into the aortic root. The hearts were then stored in an appropriate solution at 0 to 1°C for 2 hours. In the experimental group (n = 6), a solution of iopromide and custodiol were injected into the aortic root at a ratio of 50:50 under a pressure of 70-80 mm Hg for 5 minutes after 120 minutes of preservation. Then the coronary bed was washed with 1 liter of custodiol at a pressure of 40 mm Hg and orthotopic heart transplantation was performed. In the post-transplant period, the parameters of central hemodynamics, myocardial oxygen consumption, and the levels of myocardial ischemia markers (troponin I, creatine phosphokinase-MB, lactate dehydrogenase) were assessed.Results: Twelve orthotopic heart transplantations were performed during the study. In 120 minutes after the restoration of spontaneous cardiac activity, the level of cardiac output was 5.11 [4.99; 5.41] L/min and 5.77 [4.97; 6.62] L/min (p = 0.0009) in the control and experimental groups, respectively. Changes in the concentration of lactate dehydrogenase, troponin I and lactate in the blood flowing from the coronary sinus were significantly higher in the early reperfusion period. However, no statistically significant difference was observed between the groups (p > 0.05). Myocardial oxygen consumption was significantly reduced at reperfusion. However, the initial values were restored by reperfusion minute 60 without any significant intergroup difference (p > 0.05).Conclusion: We established the safety of intracoronary iopromide administration for pharmaco-cold ex vivo preservation of the donor heart. Intracoronary administration of iopromide solution does not affect the restoration of the pumping function of the heart or metabolism in cardiomyocytes in the early post-transplant period. Received 6 May 2022. Revised 14 June 2022. Accepted 11 July 2022. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, I.S. ZykovData collection and analysis: M.O. Zhulkov, I.S. Zykov, A.K. Sabetov, H.A. Agaeva, A.G. Makaev, D.M. Osintsev, A.E. Kalendarev, A.P. Nadeev, V.E. Kliver, A.R. Tarkova, M.A. Ovchinnikova, N.A. Karmadonova, D.V. KhomushkuStatistical analysis: M.O. Zhulkov, A.G. MakaevDrafting the article: M.O. ZhulkovCritical revision of the article: M.O. Zhulkov, D.A. Sirota, I.S. Zykov, A.V. FomichevFinal approval of the version to be published: M.O. Zhulkov, D.A. Sirota, I.S. Zykov, A.K. Sabetov, H.A. Agaeva, A.G. Makaev, D.M. Osintsev, A.E. Kalendarev, A.P. Nadeev, V.E. Kliver, A.R. Tarkova, M.A. Ovchinnikova, A.V. Fomichev, N.A. Karmadonova, D.V. Khomushku
Цель. Оценить эффективность и работоспособность кондуита из диэпокси-обработанной яремной вены быка в эксперименте на крупных лабораторных животных в течение 6 мес. Методы. Тринадцать кондуитов из обработанной диэпоксидом яремной вены быка имплантировали в позицию легочной артерии молодым мини-свиньям. Во время наблюдения функцию кондуита оценивали с помощью чреспищеводной эхокардиографии. Через 6 мес. животных выводили из эксперимента и проводили гистологическое исследование эксплантированных кондуитов. Результаты. Все кондуиты успешно имплантировали без хирургических осложнений. Все животные дожили до окончания периода наблюдения. Через 6 мес. у пяти из них отметили увеличение градиента на кондуите: причинами были несоответствие размеров кондуит – легочная артерия (n = 1), дистальный стеноз кондуита (n = 2), эндокардит (n = 2). За время наблюдения не выявили значительного роста регургитации на клапане или тромбоза кондуита. В кондуитах без дисфункции полностью сохранилась структура стенок и створок. Тонкий слой фиброзной ткани покрывал внутреннюю стенку кондуита с полной эндотелизацией поверхности. Дегенеративных изменений, кальцификации или воспалительных клеток в стенке или створках кондуита не было. Пролиферация неоинтимы без отложения кальция наблюдалась в двух кондуитах с дистальным стенозом. В адвентиции выявлены воспалительные клетки, состоящие из многоядерных макрофагов, лимфоцитов и гистиоцитов. В медии и интиме этих кондуитов воспалительная реакция отсутствовала, створки были не изменены. Заключение. Кондуиты из диэпокси-обработанной яремной вены быка продемонстрировали приемлемую эффективность, хорошую эндотелизацию, низкую склонность к тромбообразованию и накоплению кальция в стенке и створках. Поступила в редакцию 31 октября 2022 г. Исправлена 25 ноября 2022 г. Принята к печати 28 ноября 2022 г. Финансирование Исследование выполнено при поддержке Российского научного фонда (грант № 22-25-20102). Конфликт интересов Авторы заявляют об отсутствии конфликта интересов. Вклад авторов Концепция и дизайн работы: Н.Р. Ничай, И.Ю. Журавлева, А.В. Богачев-Прокофьев Сбор и анализ данных: Н.Р. Ничай, Ю.Ю. Кулябин, И.С. Зыков, Е.В. Бояркин, О.Ю. Малахова, Е.В. Кузнецова, Т.П. Тимченко, Я.Л. Русакова, И.С. Мурашов, А.А. Докучаева Статистическая обработка данных: Н.Р. Ничай, И.Ю. Журавлева Написание статьи: Н.Р. Ничай, И.Ю. Журавлева, Ю.Ю. Кулябин, И.С. Зыков, Е.В. Бояркин, О.Ю. Малахова, Т.П. Тимченко, Я.Л. Русакова, И.С. Мурашов, А.А. Докучаева Исправление статьи: Н.Р. Ничай, И.Ю. Журавлева, Ю.Ю. Кулябин, А.А. Докучаева, А.В. Богачев-Прокофьев Утверждение окончательного варианта статьи: все авторы
Relevance. The frozen elephant trunk technique is recognized as a safe and effective method of surgical treatment for aneurysms and dissections of the thoracic aorta. The hybrid prostheses, available on the territory of the Russian Federation, are foreign-made, characterized by a high price, and, accordingly, unpopular. Due to unavailability of domestic hybrid prostheses in the home market, the development of domestic prosthesis is the key point to further progress in aortic surgery in the Russian Federation. Aim . The aim of the study was to evaluate the implantation characteristics of prototype hybrid thoracic aorta prosthesis in the pig model and the transformation of the prosthesis in the postoperative period. Material and Methods . The hybrid prosthesis consists of two parts including the vascular part and a stent graft. The prosthesis is made of Dacron and Z-shaped nitinol wire stents. A Landrace pig aged six months with body weight of 120 kg underwent open reconstruction of the descending aorta through the left-sided lateral thoracotomy, under conditions of extracorporeal bypass with a roller pump from the left subclavian artery to the descending aorta. The animal was removed from the experiment after six months as planned. The macro- and microscopic evaluation of the removed implant was performed. Results . The technical success of implantation of hybrid stent graft prototype was confirmed. Macroscopy of the stent graft, removed after six months, demonstrated a complete coverage of the neointimal inner surface of the synthetic prosthesis. The lumen of the product was patent. Histological examination revealed the neointima presented as a structured connective tissue without signs of inflammation. The luminal surface was lined with a single layer of evenly spaced endotheliocytes. The thickness of the neointima in the vascular part was significantly greater than in the stent-graft part ( p = 0.0121). Conclusion. The study demonstrated the technical feasibility of implantation of the prototype hybrid prosthesis developed by Angioline Research LLC. The effectiveness of sealing impregnation was confirmed by the absence of active signs of bleeding during the perioperative and early postoperative stages. The prosthesis demonstrated satisfactory bio- and hemocompatibility.
КЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ ХИРУРГИЯЦель -экспериментальная апробация аппарата вспомогательного кровообращения на основе насоса вязкого трения в хроническом эксперименте.Материал и методы.Трем телятам в возрасте 3 мес была выполнена паракорпоральная имплантация аппарата вспомогательного кровообращения на основе насоса дискового типа по схеме «левое предсердие -нисходящая грудная аорта».Результаты.Разработана и апробирована методика исследования нового типа аппарата вспомогательного кровообращения на крупных млекопитающих.Проведены 3 хронических эксперимента на телятах.Длительность наблюдения в данной серии составляла 2, 5 и 7 сут.Основные показатели гемодинамики, кислотно-щелочного равновесия и биохимический состав крови находились в пределах нормы на протяжении всего периода наблюдения.Проведенные морфологические и гистологические исследования почек, печени, легких и миокарда не выявили наличия зон ишемии или тромбоэмболии.Заключение.Результаты данной серии экспериментов показали целесообразность проведения дальнейших исследований по разработке опытных образцов
Today the Russian Federation has one of the worst indicators in the world in terms of morbidity and mortality from stroke. Currently, two methods are used to treat ischemic stroke: thrombolysis and thrombextraction. However, despite their effectiveness, the methods have limited use due to the presence of strict indications and contraindications. In this regard, the search for new methods of treating ischemic stroke, which can be effective both with independent use and as an addition to already existing methods, is an urgent task. The purpose of this paper is to review research studies on the use of hypothermia in ischemic stroke. Hypothermia has a proven neuroprotective effect in cerebral ischemia. In this context, interest is the method of intracarotid selective cerebral hypothermia, which, according to a number of preclinical studies, significantly reduces the volume of cerebral infarction after ischemic stroke. The advantage of this method is the rapid achievement of the target temperature, a targeted effect on the brain and a minimal effect on the system temperature. Thus, intracarotid selective cerebral hypothermia is a very promising method for the treatment of ischemic stroke and deserves further study. In this regard, the authors decided to conduct a preclinical study on this subject. Received 9 October 2018. Revised 25 January 2019. Accepted 30 January 2019. Published online 11 March 2019. Funding: The work was funded by the Russian Foundation for Basic Research (grant No. 18-415-540025). Conflict of interest: Authors declare no conflict of interest. ORCID IDE.I. Fartakov, https://orcid.org/0000-0002-1847-7291A.R. Tarkova, http://orcid.org/0000-0002-4291-6047E.I. Kretov, http://orcid.org/0000-0002-7109-9074V.V. Lomivorotov, https://orcid.org/0000-0001-8591-6461I.S. Zykov, http://orcid.org/0000-0001-6253-9026