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This study aimed to investigate the cardioprotective effect of quinacrine in an in vivo model of myocardial ischemia/reperfusion injury. A 30-min regional myocardial ischemia followed by a 2-h reperfusion was modeled in anesthetized Wistar rats. Starting at the last minute of ischemia and during the first 9 min of reperfusion the rats in the control (n=8) and experimental (n=9) groups were injected with 0.9% NaCl and quinacrine solution (5 mg/kg), respectively. The area at risk and infarct size were evaluated by "double staining" with Evans blue and triphenyltetrazolium chloride. To assess vascular permeability in the area at risk zone, indocyanine green (ICG) and thioflavin S (ThS) were injected intravenously at the 90th and 120th minutes of reperfusion, respectively, to assess the no-reflow zone. The images of ICG and ThS fluorescence in transverse sections of rat hearts were obtained using a FLUM multispectral fluorescence organoscope. HR tended to decrease by 13% after intravenous administration of quinacrine and then recovered within 50 min. Quinacrine reduced the size of the necrotic zone (p=0.01), vascular permeability in the necrosis region, and the no-reflow area (p=0.027); at the same time, the area at risk did not significantly differ between the groups. Intravenous administration of quinacrine at the beginning of reperfusion of the rat myocardium reduces no-reflow phenomenon and infarct size., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the dynamics of the main hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with visceral obesity and chemically induced colitis (CIC) against the background of probiotic therapy. Systolic BP, HR, and body temperature were recorded over 36 days using a wireless telemetry system. During 8 days (3 days before CIC induction and until the end of the experiment) the animals were intragastrically administered a probiotic based on Lactobacillus delbrueckii D5 strain. At baseline, systolic BP was significantly higher in the SHR group, while HR and body temperature did not differ in SHR and WKY rats. On day 8 after CIC induction, systolic BP, HR, and body temperature in SHR were significantly increased in comparison with the initial values. In the group of WKY rats, all indices at the end of the experiment remained at the initial levels. Probiotic therapy in SHR, in contrast to WKY rats, did not lead to normalization of body temperature and hemodynamic disorders resulting from CIC., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

A morphological analysis of the liver of Wistar rats was performed 2 months after a single intravenous injection of porous silicon particles of different sizes (60-80, 250-300, and 500-600 nm; 2 mg/ml, 1 ml). Histological, immunohistochemical, and electron microscopic methods showed the development of CD68 + granulomas in all experimental groups. Injection of 60-80-nm porous silicon particles led to the formation of single large granulomas (>2000 μm 2 ), while 500-600-nm nanoparticles caused the formation of numerous smaller granulomas. The mechanism of involution of granulomas by apoptosis of Kupffer cells and the absence of subsequent connective tissue remodeling of the organ tissue is shown., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Here we developed a model of chronic thromboembolic pulmonary hypertension (CTEPH) using repeated intravenous administration of microencapsulated thrombi with a controlled rate of biodegradation. Autologous thrombi encapsulated in alginate microspheres with a diameter of 190±48 μm were intravenously injected to rats 8 times every 4 days. In the comparison group, nonmodified thrombi were injected. After 6 weeks, a significant increase in systolic pressure in the right ventricle, a decrease in exercise tolerance, and an increase in the index of vascular wall hypertrophy were revealed in the group receiving injections of microencapsulated thrombi in comparison with the group receiving nonmodified thrombi and healthy animals. Thus, the developed representative CTEPH model can be used to test promising pharmacological substances., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

We studied the influence of recombinant IL-2 and brain-derived neurotrophic factor (BDNF) on the size of the myocardial necrosis zone of rats with systemic inflammatory response syndrome (SIRS). A significant increase in the necrosis zone and the levels of proinflammatory cytokines was revealed in animals with SIRS in comparison with the control. The administration of IL-2 to animals with SIRS significantly reduced the size of the necrosis zone, which was paralleled by a pronounced increase in IL-2 and BDNF in comparison with the corresponding parameters in rats with SIRS that did not receive IL-2. Administration of BDNF to animals with SIRS was followed by normalization of TNFα and IL-1α levels, but did not lead to a decrease in the size of the necrosis zone., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: It is known that cardiovascular events (CVE) occur more often in winter than in summer. However, dependence of myocardial infarction (MI) risk of on various meteorological factors is still not fully understood. Also, the dependence of the seasonal dynamics of MI on gender and age has not yet been studied. The purpose of our meta-analysis is to reveal dependence of the circannual dynamics of MI hospitalizations on gender, age, and characteristics of a region's climate., Main Body: Using Review Manager 5.3, we performed a meta-analysis of 26 publications on the seasonal dynamics of MI. In our meta-analysis, the relative MI risk was higher in colder compared to warmer seasons. Old age insignificantly increased the seasonal MI risk; gender did not affect the seasonal dynamics of MI, but MI was more common in men than in women. The severity of the seasonal dynamics of MI risk depended on the climate of the region. In a climate with a small amplitude of circannual fluctuations in air temperature, atmospheric pressure, and partial oxygen density in the air, as well as in regions where air humidity is higher in winter than in summer, an increase in MI risk in winter compared to summer was significant. It was not significant in regions with opposite climatic tendencies., Conclusions: Based on the results of our studies, it can be concluded that a decrease in air temperature increases in MI risk; in addition, hypoxia in the hot season can provoke CVE associated with ischemia., (© 2022. The Author(s).)

We studied the role of both parts of the autonomic intracardiac nervous system in the pathogenesis of atrial fibrillation (AF). In 12 pigs weighing 39±3 kg, AF was induced by burst stimulation. Chemical inactivation of intrinsic cardiac neurons within the right atria was performed by transendocardial injections of liposomal neuromodulators into the dorsal part of the right atrial wall. Sympathetic and parasympathetic terminals were inactivated with 6-hydroxydopamine (6-OHDA, n=6) and ethylcholine aziridinium ion (AF64A, n=6), respectively. Neuromodulators were encapsulated in liposomes (LS) with diameters of 310±50 nm for OHDA and 290±50 nm for AF64A. LS-6-OHDA and LS-AF64A were injected into the ganglionated plexuses after measuring the baseline effective refractory period and assessing myocardial resistance to AF. These measurements were repeated 90 min after the injections. The optimal doses were 0.2 mg/kg for LS-6-OHDA and 0.4 mg/kg for LS-AF64A (in 4 ml of suspension). Immediately after injections of liposomal neuromodulators, almost all pigs showed an increase in HR, and a short-term BP elevation was observed in the LS-AF64A group. At the end of the experiment, similar decrease in the effective refractory period and similar increase in the resistance to AF were observed in all animals. Thus, selective chemical inactivation of cholinergic and adrenergic terminals of the intracardiac nervous system with liposomal neuromodulators increased the resistance to AF in an acute experiment. However, the short observation period does not allow making a definite conclusion about the role of the autonomic nervous system in the pathogenesis of AF, which requires verification of the obtained data in a chronic experiment., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The effect of probiotic therapy on the main hemodynamic parameters was studied in Wistar rats with modeled syndrome of systemic inflammatory response resulting from chemically induced colitis complicated by antibiotic-induced dysbiosis. Using a wireless telemetry monitoring system in round-the-clock mode, the mean systolic and diastolic BP, HR, and body temperature were measured over 27 days. In the group of animals receiving no probiotics, a significant decrease in feed consumption and body weight loss were observed. By the end of the experiment, BP in this group was lower by 12% and HR was higher by 10% than in the control. In animals treated with a mixture of probiotic strains Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis, all the studied parameters returned to the initial values. Thus, we demonstrated the possibility of using probiotic drugs for the treatment of acute systemic inflammatory process, which should be considered in the development of new treatment protocols in veterinary and medicine., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.

The study focuses on the effects of azithromycin on severity of ischemia/reperfusion myocardial injury during simulated systemic inflammatory response syndrome (SIRS) in primary visceral obesity (PVO). Total ischemia/reperfusion was modeled by Langendorff perfusion of isolated heart with following estimation of the size of myocardial infarction. SIRS was accompanied by an increase in blood levels of proinflammatory cytokines and LPS. Combination of PVO and SIRS produced no significant changes in the infarct size compared to the control. Administration of azithromycin to rats with PVO and SIRS resulted in pronounced alterations of biochemical and immunological parameters, although it did not affect the infarct size. In contrast, the use of tetracycline increased the size of myocardial infarction. This phenomenon should be taken into consideration in antimicrobial therapy.

For studying the possibility of using catheter denervation of the pulmonary artery for the treatment of pulmonary hypertension, large animals, such as pigs, are more suitable, because the diameter of the pulmonary artery in this case allows manipulation of the ablation catheter. The study of the perivascular adipose tissue of the trunk and bifurcation of the pulmonary artery in humans and pigs revealed differences in the density and diameter of nerve fibers, but their depth did not differ. Immunohistochemical analysis with different markers of the autonomic nervous system receptors revealed similar receptor profile in human and pigs, though the expression of all studied markers in pigs was less pronounced than in humans. These findings attest to similarity of the innervation of the pulmonary arteries in humans and pigs under normal conditions.

Morphological analysis of the respiratory tract of Wistar rats was performed after a single parenteral administration of 12-nm silicon dioxide nanoparticles (1 ml, 2 mg/ml, intravenously) was performed. On day 21 and in 2, 4, and 6 months after the administration of nanoparticles, the development of macrophage infiltration in the interstitium of the respiratory tract was demonstrated by histological and immunohistochemical methods. The pool of alveolar macrophages increased in 4 months after administration (p=0.004) and returned to the control values in 6 months. The number of mast cells did not significantly change at all stages of the experiment. Connective tissue remodeling in the interstitium of the respiratory tract was not observed throughout the observation period.

We studied the effect of metformin (100 and 200 mg/kg/day, 4 weeks) on the adenylyl cyclasestimulating effects of β-agonists and relaxin in the myocardial membranes and on activities of Akt-kinase, an effector component of insulin signaling, and AMP-activated protein kinase (AMPK), a cellular energy sensor, in the myocardium of rats with type 2 diabetes mellitus induced by high-fat diet and streptozotocin. Metformin normalized the ratio of adenylyl cyclase effects of β 1/2 - and β 3 -agonists in the myocardial membranes, that is reduced in DM2, and restored phosphorylation of Akt-kinase by Ser473 and AMPK by Thr172 in the myocardium of diabetic rats. The effect of metformin in a dose of 200 mg/kg/day was more pronounced. Thus, the cardioprotective effect of metformin is due to its ability to restore the adrenergic and insulin regulation in cardiomyocytes and their energy status.

We studied the effect of combined antimicrobial therapy with amoxicillin, metronidazole, and clarithromycin on the severity of ischemia/reperfusion myocardial injury in Wistar rats with alimentary obesity and acute inflammation of the large intestine. General ischemia/reperfusion was reproduced on Langendorff-perfused isolated hearts and infarct size was estimated. Acute inflammation of the large intestine was accompanied by an increase in the blood levels of proinflammatory cytokines. The presence of obesity and acute inflammation of the large intestine did not significantly affect the infarct size in comparison with the control. Administration of antimicrobial drugs to animals with obesity and acute inflammation of the large intestine led to a significant increase in the infarct size, which should be considered when prescribing antimicrobial therapy to patients with comorbidity.

The effects of bariatric surgeries (sleeve gastrectomy and ileal transposition) on the dynamics of changes in ghrelin level were studied in rats with severe decompensated type 2 diabetes mellitus under conditions of glucose challenge as well as on the size of myocardial infarction in these animals. Diabetes was modelled by high fat diet and a single administration of streptozotocin (25 mg/kg, intraperitoneally). Both bariatric surgeries significantly decreased glucose-induced ghrelin level in the blood of rats with type 2 diabetes mellitus, which attested to an increase in the tissue sensitivity to ghrelin. Sleeve gastrectomy resulted in a decrease in the size of myocardial infarction in diabetic rats, which was calculated as the ratio of the necrosis zone to the zone of the risk of myocardial infarction. Ileal transposition had no effect on this parameter. Our data can be used as the basis for optimization of treatment approaches when using bariatric surgery in the treatment of patients with severe forms of type 2 diabetes mellitus with a high risk of cardiovascular diseases.

Changes in morphofunctional parameters of the isolated heart subjected to global ischemia-reperfusion were studied in SPF Wistar rats with antibiotic-induced dysbiosis (AID) treated with lyophilized yeast Saccharomyces boulardii and inactivated probiotic bacteria Lactobacillus reuteri KR2017. In contrast to S. boulardii, correction of dysbiosis with L. reuteri KR2017 against the background of gastric hypersecretion and standard antimicrobial therapy led to an increase in fat content and a decrease in free and bound water in tissues and to a significant reduction in myocardial infarct size caused by ischemia/ reperfusion injury.

Cardioprotective effects of necrostatin-1 (necroptosis inhibitor) and 3-methyladenine (autophagy inhibitor) were studied on the model of long-term cold preservation of rat heart. Addition of necrostatin-1 (490 nmol/liter) or 3-methyladenine (4.5 mmol/liter) to custodiol preserving solution reduced myocardial infarction size and improved left-ventricular function during reperfusion after 8-h preservation at 4°C. Inhibition of necroptosis and autophagy contributed to the cardioprotective effect under conditions of cold preservation of the donor heart.

Using the cell model of regenerative cardiomyogenesis (formation of contracting cardiomyocyte colonies from resident stem cells), we found that the addition of cardiomyocyte-derived apoptotic bodies to the culture of neonatal myocardial cells stimulated proliferation and differentiation of cardiomyocyte precursors and the frequency of their contraction was 1.5-fold higher than in the control. Systemic administration of cardiomyocyte-derived apoptotic bodies to Wistar rats with chronic postinfarction heart failure during the early period of myocardial remodeling considerably improved the contractile function of the heart.

The cardioprotective effects of necroptosis inhibitors necrostatin-1 and necrostatin-5 were studied on the isolated heart model in rats. Intraperitoneal injection of necrostatin-1 (1.65 mg/kg) or necrostatin-5 (2.46 mg/kg) 60 min before reperfusion of the isolated heart reduced the infarction zone caused by 30-min global ischemia and 120-min reperfusion. Intracoronary injection of necrostatin-1 (44.5 μmol/liter) caused an increase of left-ventricular systolic pressure, that is produced a positive inotropic effect, but did not reduce the infarction zone.

We analyzed changes in activity of SDH, one of the most important enzymes of the Krebs cycle, in the cytoplasm of hippocampal and cortical neurons of Mongolian gerbils (Meriones unguiculatus) at the early and delayed reperfusion period after global brain ischemia. The data indicate that SDH activity in pyramidal neurons of various hippocampal areas and in neurons of II, III and V layers of cerebral cortex after 7-min forebrain ischemia depends on both the localization of these neurons and duration of the postischemic reperfusion. SDH activity in neurons significantly increased on days 2 and 7 after reperfusion.

Cardioprotective properties of dimethyl sulfoxide (DMSO) were studied in the isolated rat heart model. Intraperitoneal administration of DMSO to animals for 3 days before the experiment, but not addition of DMSO to the perfusate, reduced infarction size. Both intraperitoneal and intracoronary administration of DMSO reduced the severity of postischemic left-ventricular dysfunction.

Experiments performed on mice C57Bl/6 with the use of GFP technology showed that activation of apoptosis is a potent physiological stimulus for targeted migration of mesenchymal stem cell from the blood to tissues. The effect of apoptosis-induced targeted migration of stem cells can be used in cell therapy of damaged organs and tissues in various pathological states.

A new rat model of global cerebral ischemia-reperfusion was proposed via reversible occlusion of the major vessels originating from the aortic arch and supplying the brain. This technique can be used for the search and study of exogenous (pharmacological) and endogenous methods of brain protection from ischemia-reperfusion injury.

Silica nanoparticles as carriers for targeted drug delivery to the heart were studied. Studies of hemodynamic parameters of rats after intravenous infusion of silica nanoparticles showed no acute toxicity. Intravenous infusion of silica nanoparticles to animals with ischemia-reperfusion of the myocardium led to accumulation of the nanoparticles in the focus of injury, which attests to possibility of passive targeted drug delivery to the myocardium.

Data on the influences of diabetes mellitus on the severity of ischemic damage to the myocardium are contradictory. We report here experiments using a model based on in vivo myocardial infarcts resulting from coronary occlusion to study the resistance of the myocardium in rats with alloxan-induced insulin-dependent diabetes mellitus to prolonged ischemia, along with studies of the infarct-limiting efficacy of ischemic preconditioning. The results showed that after diabetes mellitus for six weeks, the relative size of infarcts was significantly less than in controls (39.8 +/- 8.8 and 62.3 +/- 6.6% of the size of the anatomical risk zone respectively, p < 0.01). In addition, animals with diabetes mellitus developed ischemic ventricular tachyarrhythmia significantly less often than controls. A single episode of ischemic preconditioning in animals with diabetes mellitus had a less marked infarct-limiting effect than the same procedure in controls. Thus, these data support the existence of an endogenous cardioprotective phenotype (metabolic preconditioning) in experimental diabetes. On the other hand, the efficacy of ischemic preconditioning was sharply decreased in diabetes.

The experiments with low-intensity ultrasound stimulation of isolated rat heart revealed frequency-dependent effects of ultrasound in a frequency range of 45-298 kHz on cardiac activity.

Stimulation of the isolated heart with low-intensity low-frequency ultrasound produced a positive inotropic effect (at certain ultrasound intensity). This effect manifested in increased systolic and pulse intraventricular pressures and persisted for tens of minutes after the end of sonication.