ObjectiveThis study was carried out to assess whether the remote ischemic preconditioning (RIPC) affects the inflammatory response in patients undergoing the aortic valve replacement. Methods Twenty seven patients were included into the prospective randomised study. In all cases the aortic valve replacement was performed due to the aortic stenosis under cardiopulmonary bypass (CPB). 13 patients of main group received RIPC and 14 patients formed control group. Anaesthesia was maintained either by propofol and fentanyl (7 patients in the control group, 8 patients in the RIPC group) or by sevoflurane and fentanyl (7 patients in the control group, 5 patients in the RIPC group). RIPC was induced by three 5-min cycles of lower limb ischemia and reperfusion after anaesthesia induction. Cytokines (interleukin-8 (IL-8), interleukin-6 (IL-6)) were analysed at baseline, 30 min, 12 h, 24 h and 48 h after CPB completion. Quantitative data were presented as median (25th–75th percentile). According to nonparametrically distribution, data were assessed by the Mann-Whitney U-test, a P value < 0.05 was considered as significant. Results Our study displayed the significant increase in cytokines levels after CPB completion in both groups. There were no statistical differences in IL-8 and IL-6 concentrations between groups at 30 min and 12 h after CPB. Unexpectedly we found the significantly higher IL-8 activity in the RIPC group at 24 h and 48 h after CPB: it was 12.3 (7.9; 16.5) pg/mL vs. 6.5 (5.5; 10.4) pg/mL in the control group, p = 0.03 at 24 h and 10.6 (5.8; 13.2) pg/mL vs. 5.5 (4.5; 6.1) pg/mL in the control group, p = 0.02 at 48 h. The same tendency was found in IL-6 activity, however statistical significance between the RIPC group and the control one was not confirmed: 27.6 (15.1; 38.5) pg/mL vs. 15.3 (10.5; 28.8) pg/mL, respectively (p = 0.32) at 24 h and 17.1 (13.0; 27.3) pg/mL vs. 9.9 (6.8; 17.2) pg/mL, respectively (p = 0.14) at 48 h. Conclusions This pilot study indicates surprisingly that RIPC may enhance inflammatory response after CPB. Our data suggest that large clinical trials assessing the effects of RIPC on the inflammatory response should be performed in order to study the underlying mechanisms.

No abstract

Антиапоптотическое действие прекондиционированияИшемия и в особенности реперфузия запускают процесс программируемой гибели нейронов -апоптоз, механизмы которого на сегодняшний день достаточно хорошо изучены. При прекондиционировании головного мозга (ПреК ГМ) запускаются многочисленные процессы, препятствующие апоптозу, которые могут быть связаны с активацией рецепторов, внутриклеточных киназных каскадов, транскрипционных факторов, определенных митохондриальных белков и ядерных эффекторов. Более подробная характеристика молекулярных механизмов, участвующих как в запуске апоптоза, так и в его предот-вращении в процессе наступления ишемической толе-рантности, представлена в табл. 1. Известно, в частности, что индуцируемый ПреК транскрипционный фактор -цАМФ-зависимый связывающий белок (CREB) -способствует увеличению интенсивности синтеза анти-апоптотических белков BCL2 и BCLX L . Кроме того, под действием ПреК происходит стабилизация митохондри-ального мембранного потенциала, снижается высвобож-дение митохондриального цитохрома С, а также умень-шается интенсивность синтеза каспазы 3 и снижается активность ядерного белка p53 [1]. На модели четырех-сосудистой ишемии ГМ у крыс было показано, что меха-низмы предотвращения апоптоза нейронов СА1-зоны гиппокампа под действием ишемического ПреК вклю-чают активацию фосфатидилинозитол-3ОН-киназы (PI3K) и протеинкиназы В с последующей блокировкой сигнальных путей апоптоза [2]. В частности, ишемиче-ское ПреК предотвращало транслокацию в митохон-дрии проапоптотического фактора BAD, его связывание с BCL-X L и расщепление последнего с образованием проа-поптотического фрагмента ∆N-Bcl-X L . Помимо этого,

Hyperleptinemia potentiates the effects of many atherogenic factors, such as inflammation, platelet aggregation, migration, hypertrophy, proliferation of vascular smooth muscle cells, and endothelial cell dysfunction. The present study analysed the effects of long-term hyperleptinemia in an in vivo myocardial ischemia-reperfusion model to demonstrate whether the in vivo deleterious effect also affects cardiac structure and function. Rats by were subcutaneously administered leptin for 8 days to estimate the involvement of the JAK/STAT pathway. Data from 58 male Wistar rats were included in the final analysis. Myocardial infarction (MI) was modelled by the 30-minute ligation of the main left coronary artery followed by 120-minute reperfusion. Hemodynamic measurements, electrocardiography monitoring, echocardiography, myocardial infarct size and area at risk, blood biochemical parameters, leptin, IL-6, TNF-alpha, FGF-21, and cardiomyocyte morphology were measured. Statistical analyses were performed using IBM SPSS Statistics v.26. Seven-day hyperleptinemia in rats led to increased an blood pressure and heart rate, myocardial hypertrophy, impaired LV function, an increased frequency of ischemic arrhythmias, dyslipidaemia, systemic inflammation, and an increased size of induced myocardial infarction. The blockade of the JAK/STAT signalling pathway effectively reversed the negative effects of leptin, including increased blood pressure and total cholesterol.

В обзоре проанализированы результаты экспериментальных исследований, направленных на изучение влияния ишемического и фармакологического посткондиционирования печени, головного мозга, миокарда и скелетной мышцы на экспрессию и активность индуцируемого гипоксией фактора-1α (HIF-1α) у различных видов лабораторных животных. , Shlyakhto E. V. Российский 1,2The review concerns on the experimental studies results of the influence of ischemic and pharmacological post conditioning of the liver, brain, myocardium and scelet muscle on the expression and activity of the hypoxia-induced factor-1α (HIF-1α) in various types of lab animals. Russ