Influence of Interleukin-2 and Brain-Derived Neurotrophic Factor (BDNF) on the Size of Myocardial Infarction in Rats with Systemic Inflammatory Response.

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.

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity.

Numerous experimental and clinical studies have shown the effectiveness of various probiotic strains in metabolic disorders, gastrointestinal and liver diseases, immune system pathology. The effects of probiotics on cardiovascular dysfunction are less well known. The development and validation of a new experimental model in rats, including obesity, acute colon inflammation and antibiotic-induced dysbiosis, with common characteristics of systemic inflammatory response syndrome (SIRS), became the basis for investigating the effects of probiotic drugs on myocardial resistance to ischemic-reperfusion injury (IRI) using an in vivo model of infarction after coronary occlusion. A 24% increase in myocardial infarction compared to intact animals (p < 0.05) and significant changes in leukogram, biochemical and immunological parameters were found in Wistar rats with SIRS modelling. Introduction of a mixture of strains of Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) to animals with SIRS reduced infarct size to a value close to the control. Rats treated with LA-5 and BB-12 also showed normalization of the leukocyte count, bile acids, transforming growth factor-ß, interleukins: IL-1α, IL-2, IL-6, IL-8, tumor necrosis factor-α, lipopolysaccharide and monocyte chemoattractant protein-1 in blood in comparison with the SIRS group and with the groups treated with other probiotic strains. The obtained data convincingly show the prospects for further study of the cardiotropic potential of probiotic microorganisms in translational studies.

Acute Effect of Selective Chemical Inactivation of Sympathetic or Parasympathetic Atrial Ganglionated Plexus Structures on Atrial Fibrillation Inducibility in Pigs.

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.

Effects of Bariatric Surgeries on the Size of Myocardial Infarction and Ghrelin Level in Rats with Experimental Decompensated Type 2 Diabetes Mellitus.

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.

[Contribution of nitric oxide in the mechanisms of flow-dependent vasodilation in normo- and hypertensive rats].

The aim of this study was to evaluate the role of nitric oxide (NO) in the mechanisms of arterial distensibility and intravascular pressure stability in normotensive and spontaneously hypertensive rats. The experiments were performed on the anesthetized male Wistar, Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR). The abdominal aorta was cannulated and perfused with variable blood flow rates with subsequent determination of major characteristics of regional vascular function. The blockade of nitric oxide (NO) synthase resulted in the increase in hydraulic resistance of the hindlimb vascular bed in all series of the experiments. It was associated with the decrease in the intravascular pressure stability. The obtained results provide further evidence for an important role of NO in the formation of conductivity and stability of the arterial pressure both in normo- and hypertensive rats. However, the involvement of NO in the phenomenon of flow-dependent vasodilation in SHR is unlikely. The major difference between SHR and normotensive rats involved the ability of the resistive arteries of SHR to enhance vascular conductivity in response to blood flow enhancement. Presumably, there are some unidentified additional factors that are involved in the flow-dependent vasodilation in SHR.

Passive and active target delivery of drugs to ischemic myocardium.

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.

Effect of angiotensin-converting enzyme inhibitor quadropril on dynamic parameters of vascular tone under conditions of NO synthesis blockade in normotensive and spontaneously hypertensive rats.

The role of NO in the mechanism of quadropril modulation of the flow-dependent vasodilation was examined in normotensive (Wistar) and spontaneously hypertensive (SHR) rats. The abdominal aorta was cannulated and autoperfused at different volume rates to obtain the pressure-flow curves. In the first experimental series, the blood flow-pressure dependence was measured before and after intravenous injection of quadropril (1 mg/kg). In the next series, this dependence was obtained before and after injection of NO-synthase inhibitor L-NNA (10 mg/kg) and quadropril, respectively. Quadropril potentiated vasodilation caused by an increase in perfusion volume rate in both normo- and hypertensive rats and stabilized intravascular pressure. Inhibition of NO synthesis elevated hydraulic resistance and decreased stability of intravascular pressure in normo- and hypertensive rats. In normotensive rats, these changes were promoted by a decrease in vascular distensibility. Under these conditions, quadropril pronouncedly potentiated the flow-dependent vasodilation only in SHR rats, which was revealed methodically by an increase in perfusion rate in the posterior quarter of the body. Thus, in SHR rats the quadropril-potentiated vasodilation in response to increased perfusion rate does not depend on NO synthesis.