Search

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.

Aim. To analyze ischemic and reperfusion injury characteristics, as well as myocardial performance, to identify predictors of reduced left ventricular (LV) ejection fraction (EF)

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.

Objective. The objective of this study is to develop a therapeutic strategy for protecting grafts in order to improve the efficiency of kidney transplantation (KT) using polyclonal antibodies (pAbs) through elimination of activated forms of neutrophils, chemo- and cytokines from the donor’s bloodstream, and a decrease in the level of expression of adhesion molecules on the renal vascular endothelium at the pre-transplant stage.Materials and methods. In 2017, we developed and for the first time applied a therapeutic strategy for ischemia-reperfusion injury (IRI) in a brain-dead donor (BDD). Given the limited time interval after brain death has been diagnosed, Timoglobulin (Sanofi Genzyme, France) was administered to the donor at a dose of 8 mg/kg intravenously for 6 hours. Before drug administration and immediately before the start of cold perfusion, a complete blood count and renal transplant biopsy were performed. The study group included 10 BDDs (mean age 39.3 ± 4.4 years) who received anti-thymocyte globulin (ATG). The comparison group included 10 BDDs (mean age 38.5 ± 4.3 years) who did not undergo the new strategy. Donor kidneys were transplanted to 40 recipients (average age 47.5 ± 4.3 years), who were also divided into 2 groups, depending on the graft received (with and without ATG). At the organ donation center, a biobank of specimens from donors of various categories, including those using the IRI therapeutic strategy and recipients for retrospective assessment of the effectiveness of pAbs, was formed.Results. Clinical blood test results show that in the ATG group, there was stable leukopenia (neutropenia and lymphopenia) of 1.46 ± 0.18x109/l. Fifteen (75%) recipients of kidneys obtained from donors with ATG had immediate graft function; in the control group – 10 (50%) recipients.Conclusion. Data obtained testify to the prospects of implementing the proposed strategy in clinical practice, which will improve the quality of the resulting grafts and their suitability for subsequent transplantation, prolong graft functioning due to elimination of leukocytes as a factor of IRI, prevention of early allograft nephropathy, increase in the donor pool by using expanded criteria donors (ECDs).

Background. One of the most frequent and severe complications in the early postoperative period in lung transplantation is primary graft dysfunction resulting from ischemia-reperfusion injury. There is evidence of the effectiveness of using inhaled nitric oxide in order to prevent such injury.Objective. To assess the effectiveness of nitric oxide in the intra- and early postoperative period in bilateral lung transplantation.Material and methods. We examined 43 patients who underwent bilateral lung transplantation at the N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2012-2021. The patients were divided into two groups. The study group consisted of 23 patients, whose complex of treatment included the use of inhaled nitric oxide. Patients in the comparison group (n=20) received a standard therapy. The end points of the study were: the mechanical ventilation duration, the frequency of using extracorporeal membrane oxygenation and its duration, mortality, dynamics of oxygenation index, blood lactate level, pH, base deficiency.Results. The use of inhaled nitric oxide therapy in patients in the intra- and early postoperative period during lung transplantation improved the ventilation-perfusion ratio, as evidenced by an increase in the oxygenation index by 1.1 times (p=0.128) and 1.3 times (p=0.026) at 48 and 72 hours after surgery, respectively. Meanwhile, the frequency of using extracorporeal membrane oxygenation during surgery was found to decrease by 1.2 times (p=0.033), and that after surgery decreased by 1.4 times (p=0.474); the mechanical ventilation duration decreased by 1.4 times (p=0.042); the duration of extracorporeal membrane oxygenation decreased by 1.6 times (p=0.028); mortality reduced by 8%.Conclusion. The use of inhaled nitric oxide therapy for lung transplantation had a positive effect on the intra- and early postoperative period, as indicated by an improvement in blood gas parameters, a reduction in the frequency and duration of veno-arterial extracorporeal membrane oxygenation, and the duration of mechanical ventilation.

Peroxiredoxin 6 (Prdx6) is an antioxidant enzyme in the human body that performs a number of important functions in the cell. Prdx6 restores a wide range of peroxide substrates, thus playing a leading role in maintaining redox homeostasis in mammalian cells. In addition to peroxidase activity, Prdx6 has an activity of phospholipase A2, thus taking part in membrane phospholipid metabolism. Due to its peroxidase and phospholipase activity, Prdx6 participates in intracellular and intercellular signal transmission, thereby facilitating the initiation of regenerative processes in the cell, suppression of apoptosis and activation of cell proliferation. Given the functions performed, Prdx6 can effectively deal with oxidative stress caused by various factors, including ischemia-reperfusion injury. On an animal model of rat heterotopic heart transplantation, we showed the cardioprotective potential of exogenous recombinant Prdx6, introduced before transplantation and subsequent reperfusion injury of the heart. It has been demonstrated that exogenous Prdx6 effectively alleviates the severity of ischemia-reperfusion injury of the heart by 2–3 times, providing normalization of its structural and functional state during heterotopic transplantation. The use of recombinant Prdx6 can be an effective approach in preventing/alleviating ischemia-reperfusion injury of the heart, as well as in maintaining an isolated heart during transplantation.

Many recent studies have confirmed the effect of NO and that its relative signaling pathway is important for preconditioning of the cardioprotective effect. Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injury is considered to be the ultimate goal of cardioprotection. During preconditioning, signaling is initiated from the sarcolemmal membrane and then spread into the cytoplasm via many series of enzymes, including nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC), and protein kinase G (PKG). As a result, the signal is transmitted into the mitochondria, where the cardioprotective effect occurs. It is now well established that mitochondria act to protect the heart against ischemia-reperfusion injury via the opening of the mitochondrial ATP-sensitive K+ channel and the inhibition of mitochondrial permeability transition. This knowledge may be useful in developing novel strategies for clinical cardioprotection from ischemia-reperfusion injury.

Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury.