[Social and economic burden of stroke in Russian Federation]. / Sotsial'no-ekonomicheskoe bremya insul'ta v Rossiiskoi Federatsii.

OBJECTIVE: The purpose of this study was to assess the annual socio-economic burden of stroke in the Russian Federation from the position of the state. MATERIAL AND METHODS: Based on official statistics on morbidity and mortality due to stroke (2019), the results of a survey of patients or caregivers (680 respondents) and cost indicators of 2022, the social and economic burden of stroke during the 1st year after the acute period is modeled. All cost estimates are made from the position of the state. RESULTS: In 2019 435.2 thousand cases of stroke have been registered in the Russian Federation, 30% of those patients died during the year after the acute episode, thus annually up to 1.7 million years of life are lost. According to our study, stroke accounted for 2% of all days of disability paid by Social Insurance Fund in 2019 and 9% of cases of primary receiving of disability. More than 139 thousand working people assisted their relatives who suffered a stroke, 59.2 thousand of them were forced to change jobs, 18 thousand people left work due to the need to care for a relative. The economic burden of stroke amounted to more than 490 billion rubles. or 0.3% of GDP. The average costs per 1 registered case of hemorrhagic stroke amounted to 0.93 million rubles, ischemic - 1.2 million rubles, of which about 10% are medical costs, 5% are non-medical costs and 85% are costs associated with loss of productivity. CONCLUSION: Stroke causes a significant socio-economic burden for the state in the Russian Federation, the economic losses within 1 year is equal to the 0.3% of the country's annual GDP. The main contribution to the stroke economic and social burden is not only mortality, but also disability, leading to incapacitation of patients who have suffered a stroke, as well as to a reduction in the contribution to the economy of their relatives who help and care for them.

[Effect of nibentan on dispersion of repolarization of ventricular myocardium in the rabbit].

Among factors determining development of polymorphic ventricular tachycardia torsades de pointes under influence of class III antiarrhythmic drugs great value is attributed to enhanced heterogeneity of repolarization of ventricular myocardium which can cause functional conduction blocks and development of re-entry of excitation. In this work with the help of optical mapping of electrical activity of the heart we investigated effect of nibentan (0.3 and 1 mM) on chronotopography of repolarization of epicardial surface of ventricles of isolated after Langendorf rabbit heart (n=5). For assessment of heterogeneity of repolarization we measured the following parameters: standard deviation of mean action potential duration (APDm) along mapped region (SD-APD), dispersion index (DI=1000 SD-APDm), maximal dispersion (Dmax=APDmax-APDmin). Nibentan in concentrations 0.3 and 1 mM increased APD at the level of 90% repolarization (APD90%) from 231 +/- 12 to 277 +/- 7 ms (p < 0.05) 318 +/- 7 ms (p < 0.001), respectively, but in concentration 1 mM it practically did not affect parameters of heterogeneity of repolarization (SD-APD: from 4.4 +/- 0.9 to 5.7 +/- 1.1 ms, p=0.4; DI: from 19.1 +/- 4.2 to 18.0+3.5, p=0.8; Dmax: from 16.6 +/- 2.5 to 24.8 +/- 4.3 ms, < 0.05). These results show that nibentan in the range of clinically used doses does not effect heterogeneity of ventricular myocardium. This can explain low proarrhythmic effect of nibentan.

[Ionic channels and currents in the cardiomyocytes.].

Review concerns modern views on ionic mechanism of action potential formation in cardiomyocytes. Main characteristics of cardiomyocyte ion current are described. Importance of ion current in formation of action potential phases in various regions of the heart is considered. Molecular structure and up-to-date classification of ion channels are presented. Number of genetic abnormalities which lead to appearance of arrhythmias are described.

[Pattern of excitation in isolated heart of hibernator ground squirrel Citellus undulatus].

Aim of our study was to measure conduction velocity and pattern of excitation during hypothermia in hearts of ground squirrels Citellus undulatus, known to be most resilient hibernators. We imaged electrical conduction in intact isolated hearts of summer active and winter hibernating ground squirrels at temperatures varying from +37 degrees C to +3 degrees C. Electrical activity was mapped using CCD camera (500 frames/sec) and voltage-sensitive dye di-4-ANEPPS during normal sinus rhythm and ventricular pacing. No spontaneous tachyarrhythmia was observed in all hearts at any temperature. Hearts were able to maintain spontaneous sinus rhythm and normal pattern of epicardial excitation throughout the whole range of studied temperatures. Despite responsiveness to pacing in all hearts ventricular conduction velocity was significantly reduced (about 10-fold) at low temperatures +3 degrees C. Our data provides the first direct demonstration that isolated heart of the summer active and winter hibernating ground squirrel Citellus undulatus is able to maintain normal excitation pattern in a range of temperatures from +37 degrees C to +3 degrees C.

[Antiarrhythmic Efficacy of a New Class III Antiarrhythmic Drug RG-2.]. / Antiaritmicheskaia aktivnost' preparata III klassa RG-2 na vagotonicheskoi modeli fibrilliatsii predserdii

We studied effects of a new class III antiarrhythmic drug RG-2 in a canine model of vagally-mediated atrial fibrillation (AF). RG-2 was intravenously infused to anesthetized open-chest dogs in progressive doses (5, 10, 20 and 40 mg/kg, n=6) during vagally-induced AF. RG-2 significantly dose-dependently increased atrial effective refractory period (AERP) with and without vagal stimulation, but did not change conduction velocity. Five mg/kg terminated vagally-induced AF in 4 of 6 dogs but did not prevent AF reinduction. However, additional doses of drug 20 and 40 mg/kg successfully terminated AF in 100% as well as prevented AF reinduction in 50% and 72% of cases, respectively. Activation mapping (224 epicardial electrodes) showed that under drug influence there was gradual reduction of wavelet number until termination of the reentrant excitation. AF cycle length increased before AF termination from 91+/-4 to 140+/-8 ms (p<0.01). These changes correlated with drug-induced increasing of AERP. In conclusion, the ability of RG-2 to terminate and prevent reinduction of experimental AF appears to be associated with a significant prolongation of the AERP.

[Anticholinergic Effect of a New Antiarrhythmic Class III Drug RG-2]. / Kholinoliticheskaia aktivnost' antiaritmicheskogo preparata III klassa RG-2.

In experiments on isolated rat and rabbit right atrium, a new class III antiarrhythmic drug RG-2 (0,01-1 microM) was shown to have anticholinergic action competing with 0.2-1 mM carbachol. RG-2 (0.1-1 microM) produced dose-dependent increase of APD90% in rat and rabbit atrial cells and had no effects on other action potential parameters. In presence of carbachol RG-2 produced significantly greater increase of APD90% and caused significant increase of APD50%. Thus RG-2 exerts anticholinergic action, which can take important part in RG-2 antiarrhythmic activity.

[Ionic mechanisms of cardiotropic action of a new class III antiarrhythmic drug RG-2]. / Ionnye mekhanizmy kardiotropnogo deistviia preparata III klassa RG-2.

A perforated patch-clamp analysis of the effect of a novel class III antiarrhythmic agent RG-2, on voltage-dependent currents was made in rat ventricular myocytes. In these cells, RG-2 decreased delayed rectifier outward K(+) current, I(k), in concentration dependent manner with threshold concentration 0.1 microM/l. In contrast, the drug did not have significant effects on the transient outward and inward rectifier K(+) current. RG-2 in concentration dependent manner decreased Ca(2+) current (I(Ca,L)) with threshold concentration 1 microM/l, tenfold higher than threshold concentration for I(k). We can conclude that decreasing of I(k) may explain prolongation of cardiac repolarization induced by RG-2, and contribute to its antiarrhythmic action.

[Electrophysiological experimental study of a novel class III antiarrhythmic drug RG-2]. / Eksperimental'noe élektrofiziologicheskoe issledovanie preparata III klassa RG-2.

The electrophysiologic effects of a new drug, RG-2 were studied on anesthetized open-chest dogs and on rabbit right atrial tissue. RG-2 was manufactured in Chemical-Pharmaceutical Institute in Moscow. Dogs (n=12) were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). An ECG lead II, arterial blood pressure, His bundle electrogram, atrial and ventricular bipolar electrograms were continuously monitored, recorded and then analyzed by a computerized complex for electrophysiological study. Electrophysiological variables, ECG parameters, atrioventricular conduction (His electrogram) and blood pressure were determined after sequential i.v. administration of 1, 5, 10, 20, 40 and 80 ug/kg of RG-2. Interval between injections was 60 min. RG-2 had no significant effect on PQ, QRS, S-A, A-H and H-V intervals, but the drug caused dose-dependent increase of R-R and QT intervals. Moreover, RG-2 dose-dependently increased the atrial and ventricular effective refractory periods (AERP and VERP). Maximal increases of AERP and VERP registered at 5 min after administration of RG-2 (40 microg/kg) were 46+/-2% (p<0.001 vs control) and 23+/-6% (p<0.05 vs control), respectively. In the isolated rabbit right atrial tissue RG-2 (0.01 to 1 microM) had no effects on maximal diastolic potential, action potential amplitude and Vmax, but revealed concentration-dependent increase of action potential duration at 90% repolarization level (APD90%). The maximal effects on APD90% obtained after RG superfusion at 1 microM were 26+/-7% (p<0.001 vs control). We conclude that RG-2 has significant effects of class III antiarrhythmic drugs in vivo and in vitro.

Mechanisms of vascular wall calcium relaxation.

Using the method of isometric tension measurement in isolated blood vessels, we investigated some mechanisms of action of high calcium concentrations (>3 mM) on the mechanical activity of small branches of the rat mesenteric artery. Calcium in concentrations up to 30 mM caused relaxation of the arteries (calcium relaxation). The amplitude of the effect decreased in the presence of ouabain (10(-4) M), tetraethylammonium (10(-3) M), charibdotoxin (10(-7) M) and in the potassium-free external solution in intact and denuded rings. Glibenclamide (10(-6) M), 4-aminopyridine (10(-3) M), barium (10(-3) M) and cesium (2.10(-2) M) were inefficient. Calcium relaxation of intact vessels was impaired in the presence of N(omega)-nitro-L-arginine (10(-4) M) or methylene blue (10(-4) M) but not in the presence of indomethacin (10(-5) M). The attenuation of calcium relaxation to the same extent was observed in denuded mesenteric arteries. We conclude that calcium can cause relaxation of vascular smooth muscle cells by two mechanisms. The first is mediated via the cell membrane hyperpolarization due to the activation of Na+/K(+)-ATPase and Ca(2+)-activated potassium channels. The second mechanism is endothelium-mediated and depends on the nitrogen monoxide-guanylate cyclase pathway.