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Biomedical subjects

S F Sokolov

Publications and source records attributed to S F Sokolov.

At least 19 recordsLinked to original sources

[QT rate dependence in norm and myocardial infarction].

AIM: To assess QT/RR relationship in healthy subjects and in patients with acute myocardial infarction (AMI) using long term 12-lead ECG monitoring. MATERIAL AND METHODS: We studied separately diurnal and nocturnal QT interval rate-dependence using a linear model "QT=beta+alphaxRR" in 42 patients with AMI on 2-nd week of the disease and in 14 healthy volunteers. All necessary parameters were automatically calculated from 24-hour 12 lead ECG recordings using special programs. Myocardial perfusion and infarct size were assessed using 99mTc-MIBI gated SPECT. RESULTS: Long-term ECG monitoring permitted: 1) to detect the ECG lead with most pronounced QT/RR relationship delineated by alpha(max); 2) to determine value of "deltaalpha=alpha(max)-alpha(min)", that characterized spatial heterogeneity of QT/RR relationship. In norm diurnal values of alpha(max) were significantly higher than nocturnal ones (0.207+/-0.037 vs. 0.151+/-0.035, respectively; p<0.01). The alpha(max) values correlated with the size of MI (r=0.42-0.43, p<0.01). Therefore in patients with anterior AMI who demonstrated significantly larger defects of 99mTc-MIBI uptake than patients with inferior AMI, diurnal mean value of amax remained high despite therapy with b-blockers (0.225+/-0.037), and nocturnal alpha(max) value significantly exceeded respective amax value in healthy subjects (0.216+/-0.097 vs 0.151+/-0.035, respectively; p<0.01). Patients with AMI demonstrated an increased mean Da value when compared to normal subjects (in anterior AMI 0.098+/-0.057 vs. 0.039+/-0.014, respectively; p<0.001--diurnal period; 0.104+/-0,042 vs. 0.039+/-0.022, respectively; p<0.001--nocturnal period). In anterior AMI Da values correlated with infarct size (r=0.62, p=0.001). CONCLUSIONS: A new approach to the assessment of QT rate dependence with the use of 12-lead Holter monitoring widens possibilities of the method, firstly, because of selection of most informative ECG lead that shows maximal QT/RR relationship dynamic, and, secondly due, to discovery of the new field of ventricular repolarization research by assessment of space dispersion of QT/RR relationship. In patients with AMI when compared with healthy subjects we observed a decrease of QT/RR circadian modulation, increase of the slope and space dispersion of QT/RR rate dependence.

Electrocardiography, Ambulatory↗

[Heart rate variability in patients with paroxysmal atrial fibrillation of various etiologies].

Heart rate variability (HRV) was assessed on 24 hour Holter ECG recordings from 32 healthy persons and 54 patients with paroxysmal atrial fibrillation (AF) of different etiology (hypertension, ischemic heart disease, rheumatic mitral valve disease, idiopathic AF) aged 45-73 years. Nocturnal, diurnal and 24 hour HRV was measured. Time and frequency domain HRV measures were lower in patients with AF and underlying heart disease compared with healthy persons and for most of the parameters with patients with idiopathic AF (p<0,05). Patients with idiopathic AF compared with healthy persons had higher values of high frequency power during nighttime (p<0.05), what reflected activation of parasympathetic nervous system in this category of patients.

Aged↗

[Primary pulmonary hypertension: activation of sympathico-adrenal system and free radical oxidation. Positive effects of carvedilol therapy].

AIM: To study the condition of the sympathico-adrenal system (SAS), synthesis of cAMP dependent on beta2-adrenoreceptors and parameters of free radical oxidation in patients with primary pulmonary hypertension (PPH); to examine efficacy of non-selective beta- and alpha1-adrenoblocker carvedilol in PPH patients. MATERIAL AND METHODS: Twenty patients with PPH had 6-minute walk test, ECG monitoring with assessment of heart rhythm variability (HRV). Tests for noradrenalin and adrenalin concentration in blood plasma, cAMP synthesis by blood lymphocytes in basal conditions and under stimulation with isoproterenol and forskolin, free radical oxidation were made initially, 1 and 6 months later. Ten patients received carvedilol in addition to standard therapy, 10 patients served control. RESULTS: PPH patients had higher NA in the blood, low cAMP synthesis, high malonic aldehyde, low activity of glutathionperoxidase, increased activity of superoxidedismutase and catalase of erythrocytes. The most pronounced changes in the above parameters were observed in patients with PPH FC III-IV. HRV declined in progression of cardiac failure. 6-months of combined treatment with carvedilol increased the distance of 6-min walk. Carvedilol had no effect on HRV, it reduced NA, stimulated cAMP synthesis, demonstrated no antioxidant activity. CONCLUSION: In PPH there is activation of SAS and desensitization of beta2-AR cells, oxidative stress develops. Addition of carvedilol to standard therapy with PPH improves clinical condition due to adrenoblocking properties of the drug.

Adrenergic Agents↗

[Antiarrhythmic drug allapinin: review of results of clinical investigation].

Antiarrhythmic drug allapinin has been used in clinical practice for a long time but data of investigation of its effects and mechanism of action are scanty. The aim of this review is to summarize results of clinical studies of allapinin supplementing them with personal unpublished data. The review embraces pharmacokinetics and pharmacodynamics of the drug, its efficacy in the treatment of various cardiac rhythm disturbances and side effects. The conclusion is made that clinical application of allapinin as class 1C antiarrhythmic drug according to Vaughan-Williams classification should be guided by general recommendations concerning indications and contraindications for this class of antiarrhythmic drugs. Special feature of allapinin is its high efficacy for prevention of attacks of paroxysmal atrial fibrillation.

Aconitine↗

New aminocarboxamides with class III anti-arrhythmic activity.

In the search for new anti-arrhythmic substances we discovered the class III activity of aminocarboxamides. These compounds show a prolongation of the effective refractory period. With some of them the prolongation is more pronounced after faster than after slower stimulation of the guinea pig papillary muscle. They should therefore be of interest in the treatment of cardiac arrhythmias after myocardial infarction and atrial fibrillation. The chemical synthesis, the structure-activity relationships of the new derivatives, their efficacy on the action potential duration (APD) and the effective refractory period (ERP) in vitro of isolated guinea pig papillary muscles are described and discussed in this paper. Since AWD 160-275 (13) and AWD 23-111 (14) exerted a pronounced APD90 and ERP prolongation at faster stimulation, they were selected for further electrophysiological characterization in vitro and in vivo. Anti-arrhythmic and pro-arrhythmic effects were determined in several animal models in comparison with dofetilide, sematilide, and sotalol. 13 was found to be effective in preventing programmed electrical stimulation-induced arrhythmias in anaesthetized dogs and may therefore contribute to the therapy of dysrhythmias after myocardial infarction. The pro-arrhythmic effect of 14, investigated in a model of triggered activity in chloralose-anaesthetized rabbits under methoxamine infusion, is low in comparison with other class III anti-arrhythmics.

Action Potentials↗

[A new class-III antiarrhythmic preparation among the dicyclohexylamides of aminocarboxylic acids].

The Institute of Pharmacology, Academy of Medical Sciences, jointly with AWD (Germany) has synthesized and tested a novel class III antiarrhythmic coded AWD-160-275, a derivative of dicyclohexylamides of aminocarboxylic acids. The compound was shown to prolong cardiac repolarization, to increase atrial and ventricular refractory periods, to decrease sinus nodal automatism, and to unchange intraventricular conduction. The compound proved to be superior to the reference drugs in the rate and duration of antiarrhythmic and antifibrillatory action. In therapeutical doses it has no antiarrhythmic effect. The specific feature of the agent is that there is no relation of longer effective refractory periods to the frequency of stimulation. This property may be useful in treating tachyarrhythmias.

Action Potentials↗

Pharmacology and clinical use of a new group of antiarrhythmic drugs: derivatives of tricyclic nitrogen-containing systems.

This paper is concerned with a new group of antiarrhythmic drugs: derivatives of phenothiazine and dibenzazepine which belong to tricyclic nitrogen-containing systems. It has been discovered that the transition from omega-aminoalkyl to omega-aminoacyl phenothiazine derivatives results in a decrease in psychotropic activity and an increase in cardiovascular, particularly antiarrhythmic, action. Based on structural and antiarrhythmic activity studies, the new and effective drugs ethmozine, ethacizine and bonnecor have been selected and extensively studied. Data on spectra and mechanisms of their action, obtained in different arrhythmia models, have been confirmed by clinical studies. Correlation between pharmacological properties and electrophysiological mechanisms, and differences in action of the drugs studied on brain and heart plasma membrane receptors may serve as a starting point for the further directed search for new antiarrhythmic drugs among tricyclic nitrogen-containing structures.

Animals↗

[Anti-arrhythmic therapy of patients with recurrent ventricular tachycardias after prior myocardial infarction].

An examination of 30 patients with paroxysmal ventricular tachycardias following prior myocardial infarction showed that drug tests by using invasive and noninvasive monitoring of the action of antiarrhythmic agents allowed beneficial pharmacotherapy to be chosen for their long-term use in 20% of this category of patients. The remaining 80% were resistant to antiarrhythmic drug therapy, which was associated with the highly unfavourable prognosis confirmed by 50% mortality on a 2-year follow-up. Open heart surgeries were performed in 3 cases refractory to antiarrhythmic therapy. The operations aimed at liquidating the source of tachycardia produced a full antiarrhythmic effect. The application of this method for treating patients with postinfarction cardiosclerosis is limited by severe organic heart lesion that determines the high risk of operative mortality. This makes it necessary to intensively develop other methods of non-drug therapy providing less surgical intervention and to introduce them into practice.

Adult↗

[Etatsizin efficacy in patients with ventricular tachycardias. The results of intracardiac electrophysiological research].

As many as 30 patients with different pathologies of the cardiovascular system and paroxysms of ventricular tachycardias were examined. According to the ultrasonography data, an ejection fraction was not lower than 35% in all the patients. It has been shown by electrophysiological studies that intravenous injection of ethacizine in a dose of 0.6 +/- 0.1 mg/kg prevented induction of ventricular tachycardia in 66.7% of patients. In 16.7% of patients, the drug exerted an arrhythmogenic effect that showed up by a decrease of the cycle of tachycardia. Oral administration of ethacizine in the daily dose 100 or 150 mg prevented tachycardia induction by endocardial stimulation in 20.8% of patients. The arrhythmogenic effect of the drug was recorded in 12.5% of patients. The action of ethacizine when administered by both routes was accompanied by a significant elongation of the P--Q interval, QRS complex and of the cycle of ventricular tachycardia. Continuous administration of ethacizine in the daily dose 150 mg to patients with a positive antiarrhythmic drug action (according to the electrophysiological data) prevented paroxysms of ventricular tachycardia, with the observation period being 2 to 6.5 years.

Adolescent↗

[The diagnosis and possibilities for the anti-arrhythmia treatment of malignant ventricular disorders of the heart rhythm].

Altogether 130 patients with malignant ventricular disorders of cardiac rhythm were examined to demonstrate a possibility of obtaining the diagnostically significant data with the aid of Holter's monitoring of the ECG in 89.2%, with the aid of bicycle ergometry exercise tests in 72.3%, and by means of an electrophysiological examination of the heart in 82.5% of the above-indicated group of patients. The drug testing with the use of invasive and noninvasive techniques of monitoring the action of antiarrhythmic drugs given per os makes it possible to choose effective therapy on an individual basis. The long-term use of such therapy may prevent ventricular tachycardia relapses and noticeably enhance the patients' survival. Severe organic pathology of the heart associated with a decrease of its pump function seen in the majority of patients with malignant ventricular disorders of cardiac rhythm refractory to pharmacotherapy restricts, in a considerable number of cases, the potentialities of drastic surgical treatment because of the risk of operative death. To improve the disease prognosis of these patients, it is necessary that other methods of nonmedicamentous treatment may be used, requiring a less scope of surgical intervention, such as implantation of a cardioverter-defibrillator.

Adolescent↗

[Electrophysiological mechanisms of the effect of allapinin in patients with paroxysmal supraventricular tachycardia].

An intracardiac electrophysiological study was undertaken to examine 15 patients with paroxysmal supraventricular tachycardias. Allapinin intravenously given in a dose of 0.4 mg/kg, was tested for effects. The agent was demonstrated to cause a substantial inhibition of rapid retrograde pathway function in atrioventricular nodal tachycardia and abnormal antero- and retrograde pathway function. This is the major aspect of the drug's action that prevents the development of episodes of paroxysmal supraventricular tachycardias. The agent fails to virtually affect the function of the atrioventricular node in the anterograde direction in the two types of the tachycardia. Thus, allapinin has the mechanism of action that is typical of quinidine-like drugs used in supraventricular tachycardias.

Aconitine↗

[Comparative study of the effects of verapamil, ethmozin and ethacizine on provoked attacks of atrioventricular nodal reciprocal tachycardia].

27 patients underwent serial electrophysiological studies by using transesophageal atrial stimulation. A-V nodal reciprocal tachycardia was documented by intracardiac electrophysiological examinations. Sustained tachycardia was induced in all the patients before drug administration. On day 4 after oral verapamil, 320 mg/day, ethmosine, 800 mg/day, and ethacizine, 150 mg/day, the patients were subjected to transesophageal atrial stimulation. An antiarrhythmic effect was regarded to be reached if the authors failed to induced sustained tachycardias again. Verapamil, ethmosine, and ethacizine were found to be beneficial in 21 (78%), 13 (48%) and 21 (78%) patients, respectively. A comparative analysis demonstrated that ethacisine was not inferior to verapamil, but ethmosine produced less effects than verapamil and ethacizine. The crossover and individual efficacy shown by each drug suggests that it is necessary to use the technique of serial testing and to choose beneficial drugs from a possibly wide range of medicaments for each patient.

Adult↗

[Effect of a new anti-arrhythmia drug allapinin on hemodynamics in patients with a persistent form of atrial fibrillation before and after restoration of sinus rhythm].

Echocardiographic study was performed in 24 patients with persistent atrial fibrillation (PAF) without clinical signs of circulatory failure. When treated with allapinin , all the patients with PAF showed a significant increase in heart rate (HR) and cardiac output (CO) and a decrease in total peripheral vascular resistance (TPVR). No substantial changes in the major hemodynamic parameters were found in patients with higher left ventricular dimensions; however, a significant rise in end systolic volume (ESV) was noted. There was significantly lower HR, diminished ESV, higher stroke volume and increased CO, elevated ejection fraction and TPVR with sinus rhythm. In PAF patients without apparent signs of circulatory failure, hemodynamic effects of allapinin may be accounted for by its direct vasodilatory action on the arterial bed and by its ability to affect cardiac autonomic innervation. A moderate cardiodepressive effect of the agent may be reflected by deteriorated latent signs of myocardial incompetence which are levelled off following sinus rhythm recovery.

Aconitine↗

[Changes in systemic and intracardiac hemodynamics during bicycle ergometry in patients with fibrillation arrhythmia treated with allapinin before and after sinus rhythm recovery].

In atrial fibrillation, allapinine was shown to enhance rhythm by 7% and to increase cardiac output (p less than 0.05), as well as to slightly lower mean blood pressure and peripheral vascular resistance at rest. With exercise, both in atrial fibrillation, and sinus rhythm, there was a decrease in end-diastolic and end-systolic volumes of the left ventricle (p less than 0.05), a slight drop in ventricular ejection, that was statistically significant only with sinus rhythm (p less than 0.05). Physical exercise was not followed by an apparent additional aggravation of myocardial contractility, which makes allapinine preferable for long-term application to preserve sinus rhythm in patients without evident signs of heart failure.

Aconitine↗

[The effect of allapinine on external respiratory function in patients with diseases of the cardiovascular system].

The cardiorespiratory system was studied comprehensively in 27 patients with permanent atrial fibrillation (PAF) without the clinically marked signs of circulatory failure. After allapinine treatment 15 patients with bronchial obstruction manifestations demonstrated, in the presence of lasting PAF, a significant increase of the forced expiration capacity per s and of the maximum volumetric expiration rates. The data obtained may attest to the fact that the drug has beta-stimulating properties, confirming the reported evidence.

Aconitine↗