SummaryOver 12 years of cellular therapy in cardiology, some dictinct positive results are obtained in randomized studies. However, exact mechanisms of hematopoietic stem cell actions are still unclear under these clinical conditions. Paracrine effects of cell therapy cannot explain all these effects. Enhanced neoangiogenesis upon stem cell injection is a proven mechanism for improvement of blood supply to the heart. Meanwhile, a decreased revascularization effect 3-4 years after cell therapy is followed by repeated myocardial improvement 6-9 mo after repeated cell infusions with active development of collateral vessels, thus suggesting an additional mechanism for improvement of coronary blood supply. Restoration of regulatory functions of endothelium and smooth muscle cells, including increased NO synthase activity of endothelium and its interactions with myocardiocytes may represent a probable mechanism for this action.
Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the most severe complications of pulmonary embolism (PE), characterized by poor prognosis and insuffcient effectiveness of standard treatment approaches. A small number of representative models of CTEPH make it diffcult to conduct preclinical studies of promising pharmacological substances.Objective – development and validation of the experimental model of CTEPH in rats by embolization of the distal branches of the pulmonary artery with biodegradable microspheres.Material and methods. Male Wistar rats were used for the experiments. Biodegradable microspheres (MS) based on sodium alginate and autologous blood clots (AT) were used as embolizing particles. The animals were divided into groups: control: saline solution was injected 4 times with an interval of 8 days into the tail vein; AT: according to the above protocol, 50 μL of AT was injected; MS was administered intravenously in a volume of 50 μl of MS according to two protocols: MS4: 4 times with an interval of 8 days; MS8: 8 times with an interval of 4 days. After 2 and 6 weeks after the last injection, a histological examination of the lungs was performed; after 6 weeks: echocardiographic study (TTE), right ventricular catheterization (RV) with measurement of right ventricular systolic pressure (RVSP), treadmill test, assessment of serum endothelin1 levels by the immunoassay method.Results. During the experiments, the survival rate in the MS8 group was 50 %. In the other groups, there were no animal losses. According to the treadmill test 6 weeks after the modeling of PE, exercise tolerance was signifcantly reduced in the MC4 and MC8 groups compared with the control group. TTE data indicate a signifcant increase in the diameter of the pulmonary trunk and the right ventricular outflow tract in the MC8 compared with the control and AT. There were signifcant increase in RVSP and the level of endothelin1 compared with the control only in the MS8. After 6 weeks, the index of hypertrophy of vessel wall of the pulmonary artery in the MC4 and MC8 was signifcantly higher compared with the control and AT groups.Conclusion. Based on the use of MS, administered under the MS 8 protocol, a new representative model of CTEPH has been created, which can be used to test promising pharmacological substances.
The in silico modelling of peptides complementary to lactoferrin was carried out using the Protein 3D software package and replication of the natural bonding site between pneumococcal surface protein (PSP) and lactoferrin (LF). The modeling was based on analysis of the conjugated ion–hydrogen bond systems between these proteins (CIHBS). The oligopeptide EEVAPQAQAKIAELENQVHRLE was proposed via computer modelling and synthesized using the solid phase synthesis technique, purified, and analyzed with MS and HPLC methods to confirm >95% purity. The peptide was then studied by capillary electrophoresis (CE). The CE experiments demonstrated the split of peptide zone in the presence of LF, due to complex formation and subsequent mobility change of the system peptide-protein. The reference experiments with homomyeloperoxidase and myoglobin did not show binding with LETI-11.
Introduction. The three-dimensional (3D) imaging during laparoscopic procedures can improve the quality of that surgeries. There is a shortage of publications about the potential benefits of 3D navigation in laparoscopic surgery with urological diseases. Radical prostatectomy (RPE) is known as the gold standard of treatment of localized prostate cancer (PC), and investigation of imaging technologies in laparoscopic surgery in PC patients is a hot topic. Aim. To compare the perioperative outcomes of laparoscopic RPE performed with 3D and two-dimensional (2D) imaging. Materials and methods. We performed retrospective analysis of perioperative outcomes in 146 patients who had undergone radical surgery with localized PC. All the patients were divided into 4 groups by the surgery features: 1) 2D imaging with the technique for neurovascular bundles preservation (TNVBP) (n=52); 2) 2D without TNVBP (n=46); 3) 3D with TNVBP (n=23); 4) 3D without TNVBP (n=25). We assessed operative time, intraoperative blood loss volume (IBLV), duration of the bladder drainage, positive surgical margin (PSM) detection rate, duration of the postoperative inpatient period, urinary continence recovery rate, erectile function recovery (EFR) rate. Results and discussion. In groups 1, 2, 3, 4 the operative time was 171,4±21,1, 168,3±23,2, 98,7±17,3, 92,2±22,2 min, and the IBLV was 294,2±62,1, 281,2±53,2, 144,2±31,7, 148,5±33,0 mL, respectively. PSM detection rate was 1,92±0,11%, 2,17±0,04% in groups 1, 2, while PSM had not been detected in groups 3, 4. In all the participants, duration of the bladder drainage was 5–7 days, and the full recovery of urinary continence was detected at both 6 and 12 months after the surgery. The postoperative inpatient period was 8–10 days in groups 1, 2, and 8–9 days in groups 3, 4. The EFR at 3 months after the surgery was detected in 38,4%, 28,3%, 34.8%, 28.0% of patients, while at 12 months it was detected in 59,6%, 41,3%, 82,6%, 56,0% of patients in groups 1, 2, 3, 4, respectively. Conclusion. We revealed the following features of perioperative period of laparoscopic RPE performed with 3D imaging compared to 2D: 1) the operative time was reduced by 42–45% (р<0,05); 2) the IBLV was reduced by 47–51% (р<0,05); 3) the PSM had not been detected; 4) there was the tendency to the shorter postoperative inpatient period; 5) the EFR rate was increased by 1,3–1,4 times (р<0,05), and the best EFR outcomes were obtained via 3D imaging together with TNVBP. Thus, our study demonstrates the advisability of usage of both 3D imaging and TNVBP during the laparoscopic RPE.
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.
In 2017, the European Society of Cardiology outlined the importance of the problem of diagnosing myocardial ischemia-reperfusion injury following coronary artery bypass grafting. Myocardial injury can be accompanied by a critical decline in the cardiac index and an increase in cardiac troponin I plasma levels. The prognostic value troponin I elevation after coronary artery bypass grafting is poorly understood. Objective: to determine the prognostic value of troponin I plasma levels in relation to a fall in the cardiac index after coronary artery bypass grafting (CABG). Task: To determine the probability the cardiac index falling below 2.2 for troponin I levels in the first hours, and on days 1, 2, 3, 4 after CABG. Materials and methods. The single-center, non-randomized prospective study, running from 2016 to 2019, included 336 patients admitted for elective surgical treatment of coronary artery disease. The CABG patients were divided into three observation groups: off-pump (n = 175), on-pump (n = 128), and pump-assisted (n = 33). Troponin I levels were measured in the first hours, and on days 1, 2, 3, 4 after surgery using the Pathfast Compact immunoassay analyzer. Cardiac index was measured by invasive method. Results. In patients with a cardiac index higher than 2.2, troponin I level did not exceed 0.5 ng/mL in the off-pump group, 6 ng/mL in the on-pump group, and 3.5 ng/mL in the pump-assisted group. Patients with cardiac index lower than 2.2 have comparable troponin I levels in all groups - 21 ng/mL. Troponin I thresholds on day 1 after surgery, which, when exceeded, was associated with the likelihood of the cardiac index falling below 2.2, was 3.78 ng/mL in the off-pump group, 9.67 ng/mL in the on-pump group and 17.06 ng/mL in the pump-assisted group. Conclusion. After off-pump CABG, clinically significant myocardial injury should be expected at lower troponin I levels (3.78 ng/mL) than after on-pump CABG (9.67 ng/mL) and pump-assisted CABG (14.7 ng/mL).
Цель. Оценить безопасность трансплантации аутологичных мононуклеаров костного мозга при выполнении операции аортокоронарного шунтирования в комбинированном лечении ишемической болезни сердца у пациентов с коронарной и сердечной недостаточностью. Материалы и методы. За период с 2013-го по 2016 г. в работу включено 117 пациентов, соответствующих установленным критериям. Рандомизация в группы наблюдения: группа 0-группа контроля (операция аортокоронарного шунтирования (АКШ) и интрамиокардиальное введение 0,9% раствора NaCl), группа 1-операция АКШ и интрамиокардиальное введение аутологичных мононуклеаров костного мозга (АМНКМ), группа 2-операция АКШ, интрамиокардиальное и внутришунтовое введение АМНКМ. В указанных группах проведена оценка: клинических, лабораторных (КФК МВ, миоглобин, тропонин I, HCT, Hb, К+, АВС), инструментальных (нагрузочные тесты-ишемические изменения, жизнеугрожающие нарушения ритма, эхокардиография, speсkle traсking (оценка степени деформации миокарда)-наличие дополнительных зон гипо-, акинезии, коронарография) данных. Выполнен анализ частоты послеоперационных осложнений (гидроторакс, гидроперикард, нарушения ритма); длительности пребывания в реанимационном отделении, длительности пребывания в стационаре (койко-день) и другие показатели. Через 6 и 12 месяцев оценивали общую летальность, крупные кардиальные события-развитие острого инфаркта миокарда, желудочковые нарушения ритма, онкологическую настороженность. Номер в международном регистре клинических исследований ClinicalTrial.gov Identifier:NCT02059512. Результаты. Статистический анализ показал отсутствие статистически достоверных различий в группах наблюдения по сравниваемым критериям. Заключение. Трансплантация аутологичных мононуклеаров костного мозга при выполнении операции аортокоронарного шунтирования в комбинированном лечении ишемической болезни сердца является безопасным методом. Ключевые слова: аортокоронарное шунтирование, аутологичные мононуклеары костного мозга, реперфузионное повреждение миокарда, ишемическая болезнь сердца, диастолическая дисфункция миокарда левого желудочка, сердечная недостаточность, клиническое исследование.
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