The Mechanisms of Pharmacological Preconditioning of the Brain and the Comparative Efficacy of the Drugs — Direct- and Indirect-Acting Glycogen Synthase Kinase-3β Inhibitors: Experimental Study

Лихванцев, В. В.; Гребенчиков, О. А.; Борисов, К. Ю.; Шайбакова, В. Л.; Шапошников, А. А.; Черпаков, Р. А.; Shmeleva, Evgeniya V.

doi:10.15360/1813-9779-2012-6-37

Cited by 9 publications

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“…Вышеописанным способом у животных обеих групп моделировали ишемию сердца и последующую реперфузию. В конце каждого эксперимента у животных извлекали сердце и измельчали его скальпелем в течение 30 секунд, затем с гомогенатом проводили манипуляции, описанные нами ранее [27]. Гомогенат растворяли в буфере, содержащем 0,125 М Tрис-HCl (pH 6,8), 4% додецилсульфата натрия (Sigma Chemical Co., США), 20% глицерина, 0,005% бромфенола синего (Sigma Chemical Co., США) и 10% 2β-меркаптоэтанола (Merck, Германия).…”

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Cardioprotective effect of lithium chloride on a rat model of myocardial infarction

Гребенчиков¹,

Lobanov²,

Shayhutdinova³

et al. 2019

PKiK

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Aim. To investigate the cardioprotective effect of lithium chloride in vivo on a rat model of myocardial infarction. Methods. Twelve male Sprague-Dawley rats were randomly divided into two groups of six, with both groups modelling cardiac ischaemia and subsequent reperfusion. At the start of reperfusion, 30 mg/kg of 4.2% lithium chloride solution was intravenously administered via a catheter to the test group and 0.5 ml/kg of saline solution was administered to the comparison group. A control group comprised sham-operated rats that were not injected with any drugs other than anaesthesia during making skin incision. At the end of each experiment, the total area of the risk zone and areas of the infarction zone and left ventricle were calculated for each animal using a double-staining technique with 2% methylene blue and 1% triphenyltetrazolium chloride. A further series of experiments using 15 male Sprague-Dawley rats (third group) was performed to assess the protein content of glycogen synthase-3β in myocardial tissue. The method was similar to that for the earlier experiments; however, at the end of the experiments, the hearts were removed and homogenised, following which the concentration of glycogen synthase-3β was determined using electrophoresis. Results. The group treated with lithium chloride showed a significant decrease in the area of the infarction zone compared with the group treated with saline. The difference in the indices between the two groups was >26% (p < 0.05). Conclusion. This study demonstrated that 30 mg/kg of 4.2% lithium chloride solution, administered at the onset of reperfusion, exerted a protective effect on cardiomyocytes in a rat model of myocardial infarction by reducing the area of the infarction zone compared with that in the control group. This effect was probably mediated by an almost two-fold increase in the content of the phosphorylated form of glycogen synthase-3β in the myocardium.Received 23 June 2019. Revised 6 August 2019. Accepted 7 August 2019.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributions Conception and study design: A.N. Kuzovlev Data collection and analysis: O.A. Grebenchikov Statistical analysis: A.V. Ershov Drafting the article: A.V. Lobanov, E.R. Shayhutdinova Critical revision of the article: V.V. Likhvantsev All authors approved final version to be published.

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Section: методыunclassified

Cardioprotective effect of lithium chloride on a rat model of myocardial infarction

Гребенчиков¹,

Lobanov²,

Shayhutdinova³

et al. 2019

PKiK

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Anesthetic Preconditioning of the Small Intestine in Hemorrhagic Hypotension

Ефремов

Khramykh

Govorova

et al. 2021

Obŝaâ reanimatologiâ

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Aim of the study. To investigate the preconditioning effect of sevoflurane on small intestinal mucosa in experimental hemorrhagic hypotension.Material and methods. The study was performed on a cohort of 106 male rats that included two experimental groups: one exposed to ether (Group 1, n=40) and another one exposed to sevoflurane (Group 2, n=40); two control groups included 20 intact animals, of which 10 were anesthetized with ether and 10 with sevoflurane. Six animals were excluded from the study because they died by the 2nd hour of hemorrhagic hypotension under ether anesthesia. The study parameters were measured at 15 min, 30 min, 1 h, and 2 h of hemorrhagic hypotension. Amylolytic activity of the small intestine mucosa was determined by E. A. Zabelinsky, B. W. Smith and I. M. Roe technique modified by A. M. Ugolev. The data were statistically analyzed using the nonparametric Mann-Whitney method.Results. By 15 min of hemorrhagic hypotension, the activity of amylase fractions in all small intestine regions in Group 2 animals was significantly lower vs the Group 1 rats. By 30 min of hemorrhagic hypotension, the activity of the enzyme fractions in all small intestine regions in Group 2 animals remained significantly lower than in Group 1, by an average of 2 to 9 times (P=0.01; P<0.001), and after 1 h of hemorrhagic hypotension, it was 2 and 4 times lower (P=0.02; P<0.001). By the 2nd hour of hemorrhagic hypotension, the activity of nearly all duodenal amylase fractions in the Group 2 animals remained 3-4 times lower compared to Group 1. Meanwhile, a significantly higher activity of slowly desorbing and intracellular amylase fractions vs the control group was observed in jejunum and ileum.Conclusion. In hemorrhagic hypotension under sevoflurane anesthesia, a decrease of the pancreas excretory function, stabilization of the brush border of the mucosa of all small intestine regions, including enterocyte membranes, was found during the first hour of experiment. Two hours after the hemorrhage, the biochemical evidence of brush border damage in the jejunum and ileum was revealed.

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Synthetic Analogue of Leu-Enkephalin in COVID-19 (a Prospective Clinical Study)

Magomedov

Burda²,

Misikov

et al. 2022

Obŝaâ reanimatologiâ

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One of the main problems facing intensivists when treating patients with COVID-19 is severe and critical acute respiratory distress syndrome (ARDS) with the underlying viral pneumonia. The current guidelines of the Russian Ministry of Health (Version 15 of 22.02.22) do not include drugs with a lung protective effect. This issue could be solved by administration of a synthetic analogue of leu-enkephalin.Aim. Study the eﬃcacy of a synthetic analogue of leu-enkephalin in ARDS in patients with COVID-19.Materials and methods. The study included 35 patients divided into 2 groups. Group 1 (main) patients (n=15) in addition to standard therapy received a continuous infusion of synthetic analogue of leu-enkephalin at a rate of 5 µg/kg/hour for 5 days. Patients from group 2 (control, n=20) were treated according to the Temporary Guidelines of the Ministry of Health (V.15), but without the synthetic analogue of leu-enkephalin. The radiological data, frequency, severity and evolution of respiratory complications, changes in P/F (PaO2/FiO2) ratio, as well as changes in the scores of prognostic APACHE II, SOFA, and NEWS scales were evaluated.Results. In patients taking the studied drug, the percentage of lung damage did not change with the median (IQR) of 0 [–8; 0], while in the control group it increased by approximately 10% with the median (IQR) of +10,0 [+2; +20] (P=0.001). The proportion of patients in group 1 with positive disease evolution within 5–9 days after treatment initiation was significantly higher and reached 46.7 [24.8; 69.9]%, whereas in group 2 it was 15.0 [5.2; 36.0]% (P=0.04). Also, in group 1, starting from day 4, the median P/F ratio was significantly higher than in group 2 reaching 220 [185;245] versus 127 [111;158], respectively (P=0.014). The need for non-invasive lung ventilation in group 1 on day 7 averaged 7%, while in group 2 it was as high as 45.0%, which was significantly higher than in the main group (P=0.013).Conclusions. The use of synthetic analogue of leu-enkephalin according to the specified regimen had a significant impact on the main parameters of the viral pneumonia severity. The results serve as a rationale for the development of a novel effective treatment strategy to supplement the current standard COVID-19 management.

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The Mechanisms of Pharmacological Preconditioning of the Brain and the Comparative Efficacy of the Drugs — Direct- and Indirect-Acting Glycogen Synthase Kinase-3β Inhibitors: Experimental Study

Cited by 9 publications

References 0 publications

Cardioprotective effect of lithium chloride on a rat model of myocardial infarction

Cardioprotective effect of lithium chloride on a rat model of myocardial infarction

Anesthetic Preconditioning of the Small Intestine in Hemorrhagic Hypotension

Synthetic Analogue of Leu-Enkephalin in COVID-19 (a Prospective Clinical Study)

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