Relationship between electrical myocardial instability and postinfarction remodeling in patients with ST-segment elevation myocardial infarction.

Aim      To study the clinical value of markers for myocardial electrical instability in combination with echocardiographic parameters for predicting the risk of cardiovascular complications (CVC) in the postinfarction period.Material and methods  This study included 118 patients with ST segment elevation myocardial infarction (STEMI) and hemodynamically significant stenosis of one coronary artery. A percutaneous coronary intervention (PCI) with stenting of the infarct-related artery was performed for all patients. On day 7-9 and at 24 and 48 weeks after the treatment, ECG Holter monitoring was performed, which included analyses of ventricular late potentials, dispersion of QT interval duration, heart rate turbulence (HRT) and variability (HRV), and heart chronotropic load (HCL). At baseline and during postinfarction week 12, all patients underwent echocardiography with calculation of indexes of end-diastolic volume (iEDV) and end-systolic volume (iESV) to verify the signs of left ventricular (LV) myocardial remodeling. The criteria for LV pathological remodeling included increases in iEDV >20 % and/or iESV >15 % at 12 weeks after STEMI. The group without remodeling, R(-), consisted of 79 (67 %) patients and the group with signs of LV pathological remodeling, R(+), consisted of 39 (33 %) patients. Quality of life and achieved endpoints were evaluated during 144 weeks.Results By week 48 in group R(-), the stabilization of electrical processes in the myocardium was more pronounced as indicated by a decrease in HFLA by 12 % (р=0.004) and by a fourfold increase in RMS (р=0.047). Only in this group, the baroreflex sensitivity restored; pathological ТРС decreased from 20 to 5% (p=0.002) by the end of the active treatment. Stabilization of the repolarization phase duration in various parts of the myocardium was more active in patients without pathological remodeling as shown by decreases in disp QTa (р=0.009), disp QTe (р=0.03), sd QTa (р=0.006), and sd QTe (р=0.009). This was not observed in the group R(+). The recovery of vagosympathetic balance due to leveling the sympathetic component also was more effective in the group R(-), which was reflected in increased spectral and temporal HRV indexes (р<0.05). Both groups showed reduced HCL values at 24 weeks (р=0.047 and р=0.006); however, the HCL regression remained also at 48 weeks only in the group R(-) (р=0.006). Group R(-) patients reported higher quality of life (р=0.03) than group R(+) patients. Endpoints were achieved more frequently in the group R(+): 87.1 % vs. 27.8 % (odds ratio, 11.8; 95 % confidence interval, 4.6-30.8; р=0.00001).Conclusion      Pathological myocardial remodeling in early postinfarction period is associated with electrophysiological instability of the myocardium, which results in the development of CVC and low quality of life in patients with STEMI.

[The myocardial infarction size measuring using modern methods].

An accurate quantitative assessment of myocardium necrosis area and the viable zone (stunned and hibernating) in patients with myocardial infarction is crucial for the preoperative patient selection and predicting the cardiac surgery effectiveness. Currently, researchers and clinicians are most interested in the problem of determining the viable myocardium zone. However, only the necrosis zone area directly correlates with the patients prognosis and determines the heart pathological remodeling processes. In the distant period, the data obtained can be used to predict the post-infarction period course or for analysis the relationship of the necrosis zone with arrhythmogenesis, and a number of other indicators. Thus, the necrosis zone and the viable myocardium zone are two parameters that need to be monitored in dynamics in all patients after myocardial infarction. The most accurate and reproducible method for determining the necrosis area is contrast magnetic resonance imaging of the heart, however, this technique is still inaccessible in most hospitals. In this regard, it remains relevant to estimate the necrotic myocardium area by ubiquitous non-invasive methods such as electrocardiography and echocardiography.

Early Predictors of Heart Failure Progression in Patients After Myocardial Infarction.

Aim      To identify early predictors for progression of chronic heart failure (CHF) in patients with ST-segment elevation myocardial infarction (STEMI).Material and methods  The study included 113 patients with STEMI aged 52 (95 % confidence interval, 36 to 65) years. 24-h ECG monitoring was performed with assessment of ventricular late potentials, QT dispersion, heart rhythm turbulence (HRT), and heart rhythm variability (HRV); XStrain 2D echocardiograpy with determination of volumetric parameters, myocardial strain characteristics and velocities; and measurement of brain natriuretic peptide (BNP) concentrations. The endpoint was CHF progression during 48 weeks of follow-up, which was observed in 26 (23 %) patients. Based on the outcome, two groups were isolated, with CHF progression (Prg) (26(23%)) and with a relatively stable CHF postinfarction course (Stb) (87 (77 %)).Results At 12 weeks following MI, the Prg group showed increases in left ventricular (LV) end-diastolic dimension (EDD) (р<0.05) and end-diastolic and end-systolic volumes (EDV, ESV), (р<0.01), and EDV and ESV indexes (EDVi and ESVi, р<0.01). In this group, global longitudinal strain (GLS) was decreased at 24 weeks (р<0.05) and global radial strain (GRS) was decreased at 48 weeks (р=0.0003). In the Prg group, values of strain parameters (GLS, global circular strain (GCS), and GRS) were lower at all times. At 7-9 days, 24 weeks, and 48 weeks, the proportion of patients with pathological HRT was higher in the Prg group (38, 27, and 19 % for the Prg group vs 14 % (р=0.006); 3,4 % (р=0.001), and 2.3 % (р=0.002) for the Stb group, respectively). Only in the Stb group, increases in HRV were observed (SDNNi by 13 % (р=0.001), rMSSD by 24 % (р=0.0002), TotP by 49 % (р=0.00002), VLfP by 23 % (р=0.003), LfP by 22 % (р=0.008), and HfP by 77 % (р=0.002). At 7-9 days of MI, the Stb group had greater values of SDANN (р=0.013) and HfP (р=0.01). CHF progression correlated with abnormal values of turbulence onset (TO), disturbed HRT, increased BNP levels and LV ESD, and low values of GLS, GCS, and GRS. Combined assessment of HRT, LV ESD, and GLS at 7-9 days after STEMI allows identifying patients with high risk for CHF progression in the next 48 weeks.Conclusion      The markers for CHF progression after STEMI include abnormal TO values, disturbed HRT, increased BNP levels and LV ESD, and low values of GLS, GCS, and GRS. The multifactor logistic regression analysis revealed early predictors of CHF in the postinfarction period, including abnormal TO, increased LV ESD, and reduced GLS.

Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat.

Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free (GF) mice highlight the extreme impact on brain health that results from life without commensal microbes. However, the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male SpragueDawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut-brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, decreased visceral sensitivity and a greater display of depressive-like behaviours in the forced swim test. In tandem with these clear behavioural alterations we found changes in altered CNS serotonin concentration along with changes in the mRNA levels of corticotrophin releasing hormone receptor 1 and glucocorticoid receptor. Additionally, we found changes in the expression of brain derived neurotrophic factor (BDNF), a hallmark of altered microbiota-gut-brain axis signalling. In summary, this model of antibiotic-induced depletion of the gut microbiota can be used for future studies interested in the impact of the gut microbiota on host health without the confounding developmental influence of early-life microbial alterations.

Imaging of oxygen gradients in giant umbrella cells: an ex vivo PLIM study.

O2 plays a pivotal role in aerobic metabolism and regulation of cell and tissue function. Local differences and fluctuations in tissue O2 levels are well documented; however, the physiological significance of O2 microgradients, particularly at the subcellular level, remains poorly understood. Using the cell-penetrating phosphorescent O2 probe Pt-Glc and confocal fluorescence microscopy, we visualized O2 distribution in individual giant (>100-µm) umbrella cells located superficially in the urinary bladder epithelium. We optimized conditions for in vivo phosphorescent staining of the inner surface of the mouse bladder and subsequent ex vivo analysis of excised live tissue. Imaging experiments revealed significant (≤85 µM) and heterogeneous deoxygenation within respiring umbrella cells, with radial O2 gradients of up to 40 µM across the cell, or ∼0.6 µM/µm. Deeply deoxygenated (5-15 µM O2) regions were seen to correspond to the areas enriched with polarized mitochondria. Pharmacological activation of mitochondrial respiration decreased oxygenation and O2 gradients in umbrella cells, while inhibition with antimycin A dissipated the gradients and caused gradual reoxygenation of the tissue to ambient levels. Detailed three-dimensional maps of O2 distribution potentially can be used for the modeling of intracellular O2-dependent enzymatic reactions and downstream processes, such as hypoxia-inducible factor signaling. Further ex vivo and in vivo studies on intracellular and tissue O2 gradients using confocal imaging can shed light on the molecular mechanisms regulating O2-dependent (patho)physiological processes in the bladder and other tissues.

[Forensic medical diagnostics of chronic narcotic intoxication based on the morphological findings].

The objective of the present work was to develop the forensic medical criteria for chronic narcotic intoxication based on the results of morphological studies. The internal organs from 179 cadavers were available for the examination following death from acute poisoning with narcotic substances or as a result of chronic narcotic intoxication. The studies were carried out with the use of routine histological staining techniques and an immunohistological method. The data obtained provided a basis for the development of criteria to be employed in forensic medical diagnostics of acute poisoning with narcotic drugs and chronic narcotic intoxication. These criteria include ischemia of cerebral neurons, pulmonary emphysema with the formation of foreign body-type granulomas and fibrin/erythrocyte thrombi, morphological signs of ventricular fibrillation, the picture of bacterial endocarditis, follicular hyperplasia of the lymphoid organs, chronic portal hepatitis, and nodular degeneration of the adrenal cortex associated with its atrophy.

The ion-driven permeation experiment PERMEX.

A new installation PERMEX for the investigation of ion-driven permeation through metals was designed and built. A metal membrane under investigation separates two high-vacuum chambers. In the implantation chamber, the membrane surface is irradiated with a monoenergetic deuterium ion beam with an incident energy in the interval of 100-3000 eV/D. The ion flux at the surface is in a range of 10(13)-2 x 10(14) D/cm2 s, the membrane temperature can be varied in the interval of 290-1050 K. The permeating deuterium flux from the outlet membrane surface to the volume of the second chamber (registration chamber) is measured by a quadrupole mass-analyzer. The outlet surface of the membrane can be cleaned by an argon ion beam. To approve the correct work of the setup a number of experiments were performed with Ni membranes. First results of experiments with tungsten membranes are presented.

[Protective effect of lornoxicam on development of myocardial infarction in rats under conditions of ischemia and ischemia-reperfusion].

Activation of inflammation and enzyme cyclooxygenase with formation of proinflammatory prostaglandins is a key element of development of myocardial infarction in patients with acute coronary syndrome. Basing on literature data and own experience we suggested that single intravenous injection of 230 mg/kg of nonselective inhibitor of type 1 and 2 cyclooxygenase lornaxicam in the phase of initialization of inflammation 20 min after onset of ischemia would lead to reduction of myocardial infarction volume in rats in irreversible ischemia and ischemia with subsequent reperfusion. The conducted study allowed to reveal that administration of lornoxicam in recommended for human use dose lowered mortality of animals and increased number of capillaries per one cardiomyocyte in case of irreversible coronary artery occlusion. In ischemia-reperfusion as in irreversible myocardial ischemia lornoxicam reduced volume of necrosis and degree of thinning of left ventricular wall in the region of infarction, and lowered volume of connective tissue in periinfarction zone of the myocardium in remote period.

[Protective effect of peptide semax the rat heart in acute myocardial infarction].

Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.

[Protective effect of peptide semax (ACTH(4-7)Pro-Gly-Pro) on the rat heart rate after myocardial infarction].

Semax, a member of ACTH-derived peptides family, was used in treatment of ischemic stroke in patients. It decreased neurological deficiency and reduced NO hyperproduction in the rat brain caused by acute cerebral hypoperfusion. We suggest that semax is also capable of protecting the rat heart from ischemic damage 28 days after myocardial infarction (MI) induced by left descendent coronary artery occlusion. Semax (150 microg/kg) was given i. p. in the operating day twice: 15 min and 2 hours after coronary occlusion, and once a day for the following 6 days. In 28 days after infarction, the MI group developed cardiac hypertrophy, cell growth was caused mainly by the increase of contractile filaments not supported by the appropriate mitochondrial growth that indicated an impaired energy supply of the cells. Moreover, cardiac hypertrophy was accompanied by decreased mean arterial blood pressure and cardiac contractile function and increased left ventricular end-diastolic pressure. Pharmacological change of cardiac afterload revealed that, in 28 days after MI, the rat heart was not able to change its contractile performance in response to either increase or decrease of systemic blood pressure, and as a result could not maintain its diastolic pressure. All these changes obviously reflect development of heart failure. Semax did not affect cardiac work but partially prevented end-diastolic pressure growth in left ventricle as well as ameliorated cardiomyocyte hypertrophy and disproportionate growth of contractile and mitochondrial apparatus, thus exerting beneficial effect on the left ventricular remodeling and heart failure development late after myocardial infarction.

[TT virus]. / TT virus.

Non-enveloped TT virus (TTV), recognized in 1997, contains single-stranded circular DNA (about 3,800 nucleotides) and seems to be a member of Circinoviridae, a new family of hepatitis viruses. The data on the occurrence of TTV are highly controversial: 1-22% in blood donors, 20-40% in hematological patients, 15-35% in patients with liver diseases. The virus has been found to be transmitted by the oral-fecal route as it penetrates via bile into feces and is then excreted from the gastrointestinal tract. A relatively low percentage of the occurrence of TTV infection in groups of risk may be regarded as the evidence that sexual and injection routes are not the main route of its transmission. Further investigations are necessary to establish the regularities of the epidemiology of TTV, to obtain information on its pathogenicity and on the methods for diagnosing hepatitis caused by this virus.

[Improvement in the technology of washing erythrocyte-containing transfusion media]. / Sovershenstvovanie tekhnologii otmyvaniia éritrotsitsoderzhashchikh transfuzionnykh sred.

A new device for preparing washed red cell components was proposed by the Sintez Co., Kurgan. The disposable containers were evaluated at the Center of Blood and Tissues, Military Medical Academy. The new system was found to be more effective, time-saving, cost-effective and decreased the risk of infectious complications as compared to the traditional methods for washing red cell components. Thus, the new device can be recommended for wide use in transfusion medicine.