[Drug therapy of atrial fibrillation in elderly patients.]

Currently, studies of the causes of atrial fibrillation are actively conducted. However, molecular and cellular mechanisms of atrial fibrillation have not been precisely established so far. Great success in the treatment of atrial fibrillation was achieved thanks to the development of surgical methods. However, these approaches, unfortunately, are not always applicable to elderly and senile patients. Antiarrhythmic drugs used in atrial fibrillation, exhibit a large number of side effects. Much attention of researchers is now attracted by fundamentally new directions in the drug treatment of atrial fibrillation. These include predserdno-selective antifibrillatory funds. Drugs, the action of which is aimed at at atrial remodeling, inflammation and fibrosis, so is of interest. Effective suppression of atrial remodeling, inflammation and fibrosis prevents the formation of a permanent form of atrial fibrillation. A new approach to the treatment of atrial fibrillation, taking into account the vegetative status of the patient, will undoubtedly increase its effectiveness.

[Influence of amiodarone on the spectral analysis of heart rate variability in patients with atrial fibrillation elderly and senile age.]

Atrial fibrillation is more common among elderly patients. Number of comorbidities, such as heart failure, coronary heart disease, disorders of the conduction system of the heart increases with age. Atrial fibrillation is a health problem. In developed countries, there is a high prevalence of the disease. The disease affects more than 33 million people worldwide. Spectral analysis of heart rate variability can be successfully used to evaluate the effectiveness of therapy. The use of this method gives an idea of the role of the autonomic nervous system in the regulation of chronotropic function of the heart. These data help to define conditions of manifestation of efficiency of antiarrhythmic drugs. In this study, spectral analysis were studied in patients with different forms of atrial fibrillation. The effect of amiodarone class III antiarrhythmic drug were studied this study. It is shown that the structure of spectrum of heart rate variability in patients with newly diagnosed atrial fibrillation differs significantly from that in patients with disease duration from 6 months to several years on the background of amiodarone.

[CLASSIFICATION AND PRINCIPLES OF ACTION OF ANTIARRHYTHMIC AGENTS.]

Data on the pathophysiological mechanisms of arrhythmias and the elecrophysiological mechanisms of antiarrhythmic drug action are reviewed. Development of the classification of antiarrhythmic drugs is analyzed.

[EFFICACY OF ANTIARRHYTHMIC AGENTS UNDER CONDITIONS OF STIMULATION OF THE SYMPATHETIC NERVOUS SYSTEM.]

The problem of weakening of the action of antiarrhythmic drugs under conditions of activation of the sympathetic nervous system draws increasing attention of researchers. These conditions are frequently encountered in clinical practice in cases of ischemia, myocardial infarction, and in patients with sustained ventricular arrhythmia. In addition, sympathetic, hyperactivity is a characteristic feature of serious cardiovascular diseases including heart failure. The beta-adrenergic stimulation can significantly modulate the electrophysiological action of antiarrhythmic drugs. There are significant differences in the ability of antiarrhythmic drugs to retain efficacy on the background of sympathetic stimulation. Additional administration of beta-blockers to patients with ventricular tachycardia, cardiac insufficiency, cardiomyopathy and patients after myocardial infarction is highly effective and is worth of addition al investigation. The search for drugs whose effect is not affected by sympathetic stimulation is still topical.

[Afobazole effect on heart rate variability in rats with different behaviors in the "open field" test].

The course of cardiovascular diseases is known to depend upon vegetative nervous system condition. The heart rate variability is the quantitative indicator of vegetative nervous system activity. The emotional stress reaction in rats tested in the "open field" was assessed by measuring the heart rate variability, which allowed the chronotropic cardiac function to be studied in detail and showed which part of the vegetative system (either sympathetic or parasympathetic) prevails in animals with different phenotypes of the emotional stress reaction. In rats demonstrating different behaviors in the "open field" test, changes in the heart rate variability were examined under conditions of the emotional stress response development and the treatment with non-benzodiazepine anxiolytic afobazole. It was established that the sympathetic nervous system tone prevails in stress-resistant rats, whereas in non-resistant animals, the parasympathetic system is predominating. In non-resistant rats exposed to stress, the heart rate variability decreased due to reduced power of very low frequencies, in contrast to stress-resistant animals, which showed increased power of very low frequencies. Afobazole was found to increase the heart rate variability in both animal groups. In non-resistant rats, afobazole also raised the vagus tone.

[The role of vagal control in the action of propranolol on the chronotropic cardiac function].

The effects of propranolol on the heart rate variability was studied in anesthetized outbred male rats, to which the drug was administered as intracisternal and intraperitoneal injections. Propranolol was found to increase the power of low- and high-frequency components of the heart rate. In influencing the heart rate variability, propranolol has the central mode of action. It is suggested that the ability of propranolol to increase the power of the low and high frequency components of the heart rate is related to its enhancing effect on the central cardiac vagal control.

Whether radial receptive field organization of the fourth extrastriate crescent (area V4A) gives special advantage for analysis of the optic flow. Comparison with the first crescent (area V2).

Recently, elongated comet-shaped receptive fields were discovered in the fourth extrastriate crescent (area V4A) of cats and monkeys. It was shown that the long axes of these receptive fields were oriented radially toward the centre of the retina. Such unusual "radial" organization of this extrastriate area led to the assumption that these neurons may contribute to the analysis of optic flow. To investigate this assumption we recorded activity of neurons in the V4A of cats during real motion in depth toward or away from a stationary visual scene. Responses of neurons in area V4A were compared with activity of neurons in area V2 under similar conditions of stimulation. Area V2 is known to be sensitive to motion but does not have radial organization. It was found that a substantial number of visual neurons in both areas did not fire at all when cats were exposed to motion in depth. Nevertheless, neurons with selective activation to direction of motion in depth were identified, but comparable numbers were found in both areas studied. We conclude that radial organization of the fourth extrastriate crescent does not provide any special advantage for the analysis of optic flow information.

[Comparative study of the electrophysiological properties of class iii medicinals (cardiocyclide, nibentan, sotalol) and evaluation of their efficacy in atrial fibrillation produced by auricular and vagal stimulation].

The electrophysiological properties of cardiocyclide, nibentan and sotalol and their efficacy on a model of atrial fibrillation were compared in experiments in anaesthetized dogs. The electrophysiological parameters of drugs were investigated using the method of programmed electrical stimulation of myocardium on the background of excitation of the peripheral segment of the right vagus nerve with current pulses of increasing frequency. The atrial fibrillation was produced by short stimulation (10 pulses) of the right auriculum (10 Hz, 4 thresholds). Cardiocyclide was injected in a dose of 2.5-5.0 mg/kg; nibentan, 0.25 mg/kg; and sotalol, 2.5 mg/kg. Cardiocyclide was found to prevent vagotonic atrial fibrillation in 80% of cases; under vagal stimulation this drug maintained the electrophysiological attributes and exhibited the frequency-independent action inherent in this agent. Nibentan completely retained its ability to prolong the ventricular repolarization under vagal stimulation conditions, increased the effective atrial and ventricular refractory periods, and showed the ability to prevent and eliminate the vagotonic atrial fibrillation in 80-90% of cases. Under vagal stimulation, sotalol increased the repolarization and prolonged the effective refractory atrial and ventricular periods, reduced the heart rate, and suppressed the sinus node function. The action of sotalol was frequency-dependent. Sotalol was found to prevent the vagotonic atrial fibrillation in 60% of cases.

[Effect of the class III antiarrhythmic drug nibentan in vagotonic atrial fibrillation].

Nibentan, the class III antiarrhythmic drug, was experimentally investigated in anaesthetized dogs using the model of vagotonic atrial fibrillation. Under the conditions of vagus nerve stimulation, nibentan retained the ability to prolong the ventricular repolarization and increase the effective refractory periods and to maintain the frequency-independent action on the effective refractory periods of the atrium. At the same time, nibentan did not affect conduction via the His-Purkinje system and prevented bradycardia induced by vagus stimulation. The drug was found to depress the conduction in atrium, this effect being retained on the background of vagus nerve stimulation. Nibentan has proved to be effective in preventing the vagotonic atrial fibrillation.

[A comparative study of the effects of antiarrhythmic class III drugs cardiocyclide and sotalol on the atrioventricular fibrillation caused by vagus nerve excitation in narcotized dogs].

The new class III antiarrhythmic agent cardiocyclide effectively prevents the atrioventricular fibrillations caused by the vagus nerve excitation in narcotized dogs. The electrophysiological effect of cardiocyclide was studied by method of programmed electric stimulation of myocardium on the background of excitation of a peripheral segment of the right vagus nerve by current pulses of increasing frequency. On this background, cardiocyclide exhibited characteristic effects manifested primarily by elongation of the QT and QTc intervals (corrected in accordance with the heart rate) and the effective refractory periods of both atrium and ventricles. The ability of cardiocyclide to increase the effective refractory period was retained irrespective of the drive signal frequency. A specific feature of the cardiocyclide effect on the model of vagus nerve excitation is a greater increase in the effective refractory auricular period as compared to that observed under normal conditions. Sotalol is less effective than cardiocyclide in the case of vagotonic atrial stimulation and does not prevent the bradycardia induced by the vagus nerve excitation. However, sotalol still retains its effects on the repolarization, the effective refractory auricular and ventricular periods, and the AV node under these conditions.

[Comparative study of electrophysiological mechanisms of anti-arrhythmia III class agents, cardiocyclide, nibentan, and sotalol during experimental myocardial infarction and sympathetic stimulation]. / Sravnitel'noe izuchenie élektrofiziologicheskikh mekhanizmov antiaritmicheskikh preparatov III klassa kardiotsiklida, nibentana i sotalona na fone éksperimental'nogo infarkta miokarda i simpaticheskoi stimuliatsii.

Electrophysiological mechanisms of the action of cardiocyclide, nibentan, and sotalol--antiarrhythmic agents of class III--was studied in dogs with experimental myocardial infarction induced by a two-step occlusion of the coronary artery. Cardiocyclide exhibited the properties typical of the class III antiarrhythmics by prolonging the ventricular repolarization and increasing the effective refractory periods in the atrium and ventricles. The degree of manifestation of these antiarrhythmic effects of cardiocyclide is independent of the induced heart rate, which is related to the ability of this drug to block the slow activation component (IKs) of the delayed rectified potassium current. Nibentan elongates the QT interval and increases the effective atrial and ventricular refractory periods, but the effect was dependent of the stimulation frequency. Sotalol, which also exhibited the properties of a class III antiarrhythmogen possessing beta-blocking activity, produced more pronounced inhibiting action upon the sinus node function and conduction (in comparison with the analogous effects of cardiocyclide). This is probably related to the ability of sotalol to block the cardiac adrenoreceptors. The effect of sotalol is also frequency-dependent, which is related to the blocking of rapid activating component (IKr) of) of the delayed rectified potassium current. On the background of isoproterenol infusion, cardiocyclide completely retained the electrophysiological and antiarrhythmic effects. The efficacy of nibentan and sotalol with respect to the repolarization and refractoriness significantly decrease under the conditions of sympathetic nervous system activation. The ability of sotalol to suppress the sinus node function and conduction on the background of isoproterenol infusion is retained.

[Electrophysiological effects of ethacizine in experimental myocardial infarction and stimulation of sympathetic heart innervation]. / Elektrofiziologicheskie éffekty étatsizina pri éksperimental'nom infarkte miokarda i stimuliatsii simpaticheskoi innervatsii serdtsa.

The electrophysiological effect of ethacizine, an antiarrhythmic agent of class IC, was studied in dogs with experimental myocardial infarction under the beta-adrenergic stimulation conditions. It was found that ethacizine (i) slows down the atrioventricular conduction and the AV-node conduction; (ii) increases the time of the sinus node function recovery; and (iii) increases the effective atrioventricular refractory periods. Under the conditions of isoproterenol-induced stimulation of the beta-adrenergic structures, some of the ethacizine effects (e.g., increased refractoriness) completely disappeared and the other (slowed down conduction) decreased. As the stimulation frequency was increased, the effect of ethacizine upon the conduction exhibited a decrease. Upon the isoproterenol injection, dependence of the QRS complex on the forced rhythm frequency disappeared.

[Use of celluloid in the production of toys]. / O primenenii tselluloida dlia proizvodstva igrushek.

Sanitary and toxicological investigations of migration and toxicity of chemical substances from celluloid were made. It was concluded that celluloid may be used in the manufacture of toys.

[The effect of antibodies to microorganisms in a focus of purulent inflammation]. / Vliianie antitel na mikroorganizmy v ochage gnoinogo vospaleniia.

The rats were infected with a suspension of dissociated or agglutinated Pseudomonas aeruginosa [correction of B. pynocyaneus]. Infection with the agglutinated agent drastically improved the clinical course, lowered the indices of the process generalization (mortality, metastatic foci, spread in the internal organs); no hemorrhages, necrosis or abscesses were noted. A rapid (within the first day) death of almost all agglutinated bacteria in the primary focus was observed, this not being due to phagocytosis or complement-dependent lysis.