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.
According to global health statistics, respiratory diseases, together with infectious complications and hereditary lung diseases, rank as the third leading cause of death. Today, lung transplantation (LTx) is a well-recognized modality of treatment for end-stage chronic lung disease. However, the number of LTx surgeries performed is much lower than other solid organs. This is due to the high requirements for the potential donor and characteristics of the lung graft, reflecting the efficiency of gas exchange function. Non-compliance with the selection criteria leads to deselection of donors, which, according to various estimates, occurs in 80–85% of cases. One of the ways to increase the number of lung transplant surgeries is to restore them to the level of optimal gas exchange parameters, which can be achieved and objectively assessed during normothermic ex vivo lung perfusion (EVLP). EVLP is becoming increasingly common at leading transplantation centers in Europe and North America. This has significantly increased the number of transplant surgeries as a result of using lungs procured from suboptimal donors and rehabilitated via EVLP. In our pilot study, the developed Russian-made mechanical circulatory support system showed that performing normothermic EVLP for isolated lungs under experimental conditions is feasible. Basic and optimized perfusion protocols have fully shown that they are reliable and efficient.
The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.
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