Diabetes mellitus — metabolic preconditioning in protecting the heart from ischemic damage?

The negative impact of diabetes mellitus (DM) on the cardiovascular system has been confirmed by numerous clinical studies. However, there are experimental studies that show an increase in the resistance of the heart to ischemic and reperfusion damage in animals with DM. This phenomenon is characterized by a smaller size of the infarct zone, better preservation of the contractile function of the myocardium, and a lower incidence of ischemic and reperfusion arrhythmias. It is assumed that at a certain stage in the development of DM, a “metabolic window” is formed, in which metabolic alterations at the cellular level trigger adaptive mechanisms that increase the viability of cardiomyocytes. Published data confirm that the magnitude of the protective effect induced by DM is comparable to, and in some cases even exceeds, the effect of the preconditioning phenomenon. It is recognized that the mechanisms that protect the heart from ischemic and reperfusion damage against the background of DM are universal and are associated with the modulation of the antioxidant system, apoptosis factors, pro-inflammatory cytokines, and signaling systems that ensure cell survival. The one of the main pathogenic factor in DM is hyperglycemia, but under stress it plays the role of an adaptive mechanism aimed at meeting the increased energy demand in pathological conditions. Probably, at a certain stage of DM, hyperglycemia becomes a trigger for the development of protective effects and activates not only signaling pathways, but also the restructuring of energy metabolism, which makes it possible to maintain ATP production at a sufficient level to maintain the vital activity of heart cells under ischemia/reperfusion conditions. It is possible that an increased level of glucose, accompanied by the activation of insulin-independent mechanisms of its entry into cells, as well as the availability of this energy substrate, will contribute to a better restoration of energy production in heart cells after a infarction, which, in turn, will significantly reduce the degree of myocardial damage and will help preserve the contractile function of the heart. Identification of the conditions and mechanisms of the cardioprotective phenomenon induced by DM will make it possible to simulate the metabolic state in which the protection of cardiomyocytes from damaging factors is realized

Inhibitory mechanism of influence of thyroid hormones on cognitive function of the brain.

In experiments on young rats there were stu­died changes in the fatty acid spectrum of fraction of  free fatty acids (FFA) of neocortex and hippocampus in con­ditions of thyroid dysfunction. Elevated levels of thyroid hormones caused accumulation of polyunsaturated linoleic and linolenic acids in the neocortex by 2 times, in the hippocampus – by 52%. State of hypo­thyroidism also contributed to the increase of C18: 2,3 in the neocortex by 74.4%. Growth of share of unsaturated fatty acid fraction in the content of fatty acid spectrum of neocortex also was accompanied by decrease in saturated C16:0 and C21:0 by 25% and 36% res­pectively. Increase of the level of unsaturated fatty acids fraction of the cerebral cortex is possibly associated with the decrease in "unsaturation" structure of lipids, which in its turn may enhance serotonergic synaptic activity. Research of concentration of neuromediator amino acids in neocortex showed increase of serotonin content both in conditions of hyperthyroidism and hypothyroidism. In conditions of hyperthyroidism increased content of GABA was observed. Activity of serotonin- and GABA- ergic neurotransmitter systems of the brain in conditions of hyperthyroidism can be considered as increase of inhibitory processes in the  effect of feedback. In conditions of experimental hypothyroidism activation of the inhibitory effects of CNS serotonergic system may be one of the ways to reduce the metabolism

Structural and functional indicators of the heart of patients with ischemic heart disease and type 2 diabetes mellitus. Rhythmoinotropic response isolated myocardium at different levels of glycated hemoglobin

BACKGROUND: Adequate glycemic control can significantly reduce the risk of developing cardiovascular events. However, until now, glycaemic targets in aged patients remain a subject of discussion, especially in the conditions of the combined development of Type 2 Diabetes Mellitus (T2DM) and ischemic heart disease (IHD).AIMS: To examine the structural and functional heart parameters in patients with IHD associated with T2DM and the rhythmoinotropic responses of their isolated myocardium depending on glycated hemoglobin level.MATERIALS AND METHODS: The study included 44 patients with a diagnosis of "chronic IHD associated with T2DM", of which 2 groups were formed. Patients with glycated hemoglobin level (HbA1c) <8% were included in the 1st group, and patients with HbA1c ≥8% were included in the 2nd group. The structural and functional heart parameters obtained with ultrasonography, and the rhythmoinotropic responses of myocardium in patients ex vivo were analyzed using the right atrial appendage fragments obtained during elective coronary artery bypass graft. The inotropic response of muscle strips at a basic stimulation frequency of 0,5 Hz to testing influences was assessed. An extrasystolic test and post-rest test were performed.RESULTS: It was found that extrasystolic contractions of isolated myocardial strips in patients of the 2nd group appeared at shorter extrasystolic intervals, which indicates a greater excitability of the myocardium in patients of this group. Postextrasystolic muscle contractions in patients of the 2nd group had significant potentiation. The amplitude of the muscle strips contractions in patients of both groups was potentiative after short rest periods. However, with an increase in the rest duration, potentiation of contractions was observed only in the group with a higher HbA1c level. According to the ultrasonography data, it was found that the values of the endsystolic and diastolic volumes, the interventricular septum thickness and the left ventricular (LV) myocardium mass were significantly lower in the patients of the 1st group compared with the corresponding indicators in the patients of the 2nd group. The early LV filling velocity (peak E) was significantly lower in the patients of the 1st group, which indicates a slower LV relaxation. At the same time, the rapid LV filling velocity did not have a significant intergroup difference, but this indicator exceeded the reference values in both groups.CONCLUSIONS: With a moderately increased glycemic level (9,2 [8,0; 10,3]%), the structural and functional heart parameters are preserved both at the level of the isolated myocardial tissue and at the level of the whole heart

Heisenberg Evolution WKB and Symplectic Area Phases

The Schrodinger and Heisenberg evolution operators are represented in quantum phase space by their Weyl symbols. Their semiclassical approximations are constructed in the short and long time regimes. For both evolution problems, the WKB representation is purely geometrical: the amplitudes are functions of a Poisson bracket and the phase is the symplectic area of a region in phase space bounded by trajectories and chords. A unified approach to the Schrodinger and Heisenberg semiclassical evolutions is developed by introducing an extended phase space. In this setting Maslov's pseudodifferential operator version of WKB analysis applies and represents these two problems via a common higher dimensional Schrodinger evolution, but with different extended Hamiltonians. The evolution of a Lagrangian manifold in the extended phase space, defined by initial data, controls the phase, amplitude and caustic behavior. The symplectic area phases arise as a solution of a boundary condition problem. Various applications and examples are considered.Comment: 32 pages, 7 figure

Allogeneic biomaterial: a fibrosis inhibitor in ischemic myocardial damage

Injectable allogeneic decellularized biomaterials are being developed both as scaffolds for delivery of cellular products and as independent pharmacological agents that affect the cascade of tissue reactions during the period of post-ischemic myocardial remodeling. Biomaterial degradation products can affect cellular processes and modulate cytokine effects, thus determining the healing strategy of damaged tissue. In this work, the influence of biomaterial on the expression of key fibrogenic factors by the cells of tissue bed was demonstrated, and the degree of damage to the myocardium during its ischemic damage was experimentally determined. The aim of our study was to determine the area of myocardial scar degeneration and detection of key fibrogenic factors (bFGF-1, TGFb1, MMP-9), as well as TIMP-2 (MMP-9 antagonist) at the acute and subacute stages of myocardial infarction after implantation of allogeneic powder-like biomaterial in an experimental model.In the course of experiments, the left ventricular coronary artery was ligated in male Wistar rats (experimental group). All animals were divided into 3 groups: experimental group I (n = 50), experimental group II (n = 50), and controls (n = 50). In experimental group I, the artery ligation was simultaneously accompanied by intramyocardial administration of powder-like biomaterial suspension (2 mg). In experimental group II, the allogeneic powder-like biomaterial was administered 5 days after coronary occlusion, and only physiological saline was administered in the control group. The animals were withdrawn from experiment on days +3, +7, +14, +30, and +45. Standard histological assessment (hematoxylin and eosin staining, according to Mallory) and immunohistochemical examination (MMP-9, TGFb1, bFGF-1, TIMP-2) were made, and statistical evaluation was performed. The cells with positive staining were counted, and the scar area index was calculated.We have found that administration of dispersed allogeneic biomaterial was followed by a five-fold decrease in the degree of scar degeneration in both experimental groups at the acute and subacute stages of ischemic myocardial damage as compared to the control group. A significantly decreased expression of fibrogenic factors (MMP-9, TGFb1, bFGF-1) by the local cells was found, along with increased activity of metalloproteinase inhibitor (TIMP-2) in connective tissue cells.Decellularized allogeneic powder-like biomaterial serves as a fibrosis inhibitor and promotes cardioprotection during myocardial remodeling at the initial stages after ischemic injury

Exposure of Nuclear Track Emulsion to a Mixed Beam of Relativistic 12^{12}N, 10^{10}C, and 7^7Be Nuclei

A nuclear track emulsion was exposed to a mixed beam of relativistic $^{12}$N, $^{10}$C, and $^7$Be nuclei having a momentum of 2 GeV/$c$ per nucleon. The beam was formed upon charge exchange processes involving $^{12}$C primary nuclei and their fragmentation. An analysis indicates that $^{10}$C nuclei are dominant in the beam and that $^{12}$N nuclei are present in it. The charge topology of relativistic fragments in the coherent dissociation of these nuclei is presented.Comment: ISSN 1063-7788, Pleiades Publishing, Ltd., 201

Features the interaction of functional and metabolic remodeling of myocardium in comorbid course of ischemic heart disease and 2 type diabetes mellitus

Background: Metabolic and structural changes in cardiomyocytes in diabetes mellitus lead to aggravation of contractile myocardial dysfunction in coronary heart disease (CHD). The contractility dysfunction of cardiomyocytes is determined by a change in the levels of sarcoplasmic reticulum (SR) Ca2+-ATPase and energetic supply of the cardiomyocytes. Aims: To study the features of functional remodeling of the heart muscle in coronary heart disease with and without type 2 diabetes mellitus (DM2) depend on the level of Ca2+-ATPase and the activity of enzymes involved in energy metabolism. Materials and methods: The work was performed on the heart biopsy of patients with CHD and patients with CHD combined with DM2. The inotropic reaction of myocardial strips on rest periods was assessed. The expression level of Ca2+-ATPase, the activity of enzymes succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) and the intensity of oxidative phosphorylation processes were determined. Results: The interval-force relationship in patients with CHD with and without DM2 had both negative and positive dynamics. The positive dynamics corresponds to the "high content" of the Ca2+-ATPase and the negative dynamics corresponds to the "low content" were found. At the combined pathology the positive inotropic dynamics is more pronounced and corresponds to a higher protein level. In the patients myocardium with CHD the activity of SDH and LDH was higher, while the oxygen uptake rate by mitochondria was higher in the myocardium with combined pathology. Conclusions: The potentiation of inotropic response of patient myocardium with CHD with and without DM2 corresponds to the "high level" of Ca2+-ATPase. In the combined pathology the inotropic capabilities of the myocardium are more expressed. In CHD the synthesis of ATP in cardiomyocytes is realized mainly due to glycolytic processes and Krebs cycle. In combined pathology the ATP synthesis is realized to a greater extent due to the oxidative phosphorylation