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.
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.
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
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
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.
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 the study is to evaluate the efficacy of various types of hybrid technology in compare to the classical repair of the aortic arch of type I aortic dissection treatment in the in-hospital period.Materials and Methods. A retrospective observational study has been conducted, the results of surgical treatment of 213 patients with DeBakey type I aortic dissection operated on within the period from 2001 to 2017 were compared. Patients were divided into three groups: in group 1, patients undergone a hemiarch type of aortic repair or the total arch replacement (n=121); in group 2, a hemiarch aortic reconstruction and implantation of bare metal stent was performed (n=55); in group 3, a frozen elephant trunk technique was used (n=37). Taking into consideration the retrospective character of the investigation and nonequivalence of the groups by separate characteristics, they were equalized to improve the reliability of the results using the PSM (propensity score matching) pseudorandomization method. As a result, three groups of comparison were formed which were equalized by the PSM method and called PSM 1, 2, and 3. The mortality and complication rate in the in-hospital period, as well as the frequency of false lumen thrombosis development depending on the treatment method, have been analyzed.Results. The mortality rate in the PSM 1 group was 15 patients: group 1 (standard technique) - 10 patients (9%), group 2 (uncoated stents) - 5 patients (11%). A significant difference was found in the number of major bleedings (group 1 - 8%, group 2 - 21%, p=0.031) and cases of bowel ischemia (group 1 - 1%, group 2 - 9%, p=0.028). Complete false lumen thrombosis of the thoracic aorta was observed significantly more often in group 1 than in group 2 (22% vs 5%, p=0.015).In the examined group PSM 2, hospital mortality rate was 4 patients: group 1 - 3 patients (12%), group 3 - 1 patient (3%). No differences between the groups were found in the number of complications. In group 3, complete false lumen thrombosis of the thoracic aorta was observed in 59% of cases, whereas in group 1 it was found only in 4% of patients (p<0.001).In comparison group PSM 3, the mortality was 8 patients: group 2 - 5 patients (11%), group 3 - 3 patients (9%). The number of neurological complications differed significantly: in group 2 - 27%, in group 3 - 6% (p=0.019). Besides, 3% of cases of complete false lumen thrombosis were found in group 2, while there appeared 55% (p<0.001) of such patients in group 3.Conclusion. The comparative analysis showed that the use of bare metal stents and hybrid prostheses demonstrated a comparable low level of in-hospital mortality compared to the standard surgical technique of aortic arch reconstruction. At the same time, the use of the bare metal stents is associated with a higher rate of perioperative complications (bleeding, postoperative bowel ischemia, neurological complications) compared to the standard treatment and repair of the aortic dissection using hybrid prostheses. Complete thrombosis of the false lumen occurred significantly less commonly in case of using bare metal stents than with standard treatment and hybrid prostheses.