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.
Prosthetic heart valves are widely used biomedical devices. The need for these prostheses is increasing due to the increasing life expectancy of the general population and the consequent incidence of age-related degenerative valvular defects. However, even though mechanical prosthetic valves have been significantly modernized over the last decades, they are still associated with several life-threatening complications, the main one being thrombosis. Addressing this problem is challenging and requires collaboration between bioengineering and cardiothoracic surgery. Thus, the problem of creating the most adapted model of prosthetic heart valve (PHV) turns out to be at the confluence of sciences – medicine, biology, applied mechanics, mathematical modeling, etc. Today, it seems clear that the engineering ideas for hemodynamic adaptation of PHV models have been fully developed. However, research in the field of materials science, as well as a search for surface modification methods, remain a pressing bioengineering challenge.
Цель. Провести сравнительный анализ отдаленных результатов применения голометаллических стентов и гибридных протезов при лечении расслоения аорты I типа.
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.
Acquired heart defects have a high prevalence among patients of different age groups and represent a significant social problem. To date, surgery remains the only effective option to treat acquired heart disease, and replacement of the dysfunctional heart valves frequently relies on mechanical prosthetic heart valves which implantation requires lifelong anticoagulant therapy with vitamin K antagonists and constant monitoring of international normalised ratio. However, the optimal target range for international normalised ratio values remains poorly defined. Optimisation of the approaches to anticoagulant therapy for this category of patients is becoming increasingly important. This paper highlights the main problems and possible solutions for patients who have undergone implantation of mechanical heart valves and need constant intake of vitamin K antagonists.
ТРАНСПЛАНТОЛОГИЯ И ИСКУССТВЕННЫЕ ОРГАНЫ ■Хроническая дисфункция пересаженных легких остается одной из главных причин смерти реципиентов в отдаленные сроки после трансплантации.Одним из возможных путей решения данной проблемы может быть полное анатомическое соединение всех структур пересаживаемого легкого
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.
The aim of the study is to analyze predictors of lethality, false lumen thrombosis, enlargement of aortic diameter, and frequency of aorta-related events in the early and remote postoperative periods for various types of proximal aortic dissection surgery using the logistic regression method. Materials and Methods:A retrospective observational comparison of the results of surgical treatment of 213 patients with the diagnosis of "DeBakey type I aortic dissection" has been carried out. The participants were divided into three groups: group 1 underwent classic aortic arch reconstruction using hemiarch technique or total reconstruction of the aortic arch with a multiple-branch prosthesis (n=121); group 2 was subjected to the hemiarch technique and implantation of bare-metal (uncoated) stents (n=55); in group 3, the "frozen elephant trunk" correction technique was used (n=37). The diagnosis of all patients included into the study was preoperatively confirmed by ultrasound and tomographic examination. Predictors of negative events have been identified by building the models of logistic regressions. Results:The multivariate model of logistic regression has revealed multiplicative significant predictors of lethality: postoperative neurological complications increased the probability of lethality by 3.39 (1.24-9.18) times and presence of a patent false lumen by 4.17 (1.49-13.68) times.Among the predictors of aorta-related events, the most important were connective tissue diseases (the probability increased by 6.68 (2.98-15.62) times), presence of partial thrombosis of the false lumen (the probability of event development increased by 2.39 (1.07-5.44) times), and aortic valve repair (the probability aorta-event occurrence increased by 2.84 (1.13-7.17) times).Hybrid prosthesis implantation appeared to be the most significant predictor of false lumen thrombosis increasing its probability by 4.19 (1.90-9.44) times among aortic repair methods, while a bare-metal stent implantation in contrast reduced the likelihood of false lumen thrombosis by 0.17 (0.03-0.62) times. Eventually, the type of repair had not any significant impact on the aorta-related events and lethality in the long-term period.
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.
Cardiac injury remains one of the most complex conditions in emergency surgery. Only 6% of patients with penetrating heart wounds manage to be delivered to the operating room for surgery, and the mortality rate is still extremely high. Unfortunately, such emergency interventions are often performed in institutions lacking the ability to provide the full range of reconstructive techniques, resulting in suboptimal correction and a high risk of developing postoperative complications. This paper describes a clinical case of successful repair of multiple stab wounds to the heart with concomitant anterior descending artery injury followed by severe heart failure requiring biventricular mechanical circulatory support.
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.
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
For a number of centuries, the problem of bleeding arrest from damaged vessels remains the major issue of surgery (alongside with infectious complications and fight against the pain syndrome). The development of vascular surgery began exactly when bleeding from a damaged vessel was arrested by tying it, and the introduction of reconstructive vascular surgery, being one of the most outstanding achievements of the 20th century, was the peak of creation. With the advent and development of this relatively young branch of clinical surgery, it became possible to effectively help patients with various vascular pathologies, previously considered incurable and doomed to death. However, the development of each industry is necessarily associated with the development of technical support. The lack of high-quality suture material and instruments has restrained the development of reconstructive vascular surgery for a long time; this fact forced researchers and surgeons to develop techniques for the seamless connection of blood vessels. Despite the widespread use of manual surgical suture, it is not always possible to use this option due to altered vascular walls. Development of technology for manufacturing synthetic materials allowed for techniques providing fast and high-quality connection of blood vessels, significantly reducing the time required for reconstruction and, as a result, reducing the incidence of complications.