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L V Rozenshtraukh

Publications and source records attributed to L V Rozenshtraukh.

At least 19 recordsLinked to original sources
PubMed2006

[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.

Action Potentials↗
PubMed2006

[Peculiarities of regulation of cardiac function in some mammals].

We studied acetylcholine induced changes of action potentials (AP) in ventricles and atria of bat, hedgehog, yakut ground squirrel, and laboratory mice. In atria of all these species of mammals acetylcholine caused pronounced dose dependent shortening of AP. However sensitivity of ventricles of studied animals to acetylcholine was different. Acetylcholine induced AP shortening was 29.4, 42.1, 6.6 and 11% in ventricles of bat, hedgehog, laboratory mice and ground squirrel, respectively. Ventricles of none of previously studied mammals had sensitivity to acetylcholine comparable by magnitude to acetylcholine sensitivity which we found in hedgehog and bat. It is suggested that these animals have unique nervous regulation of cardiac action, principally different from that of other mammals, which do not require parasympathetic regulation of ventricles.

Acetylcholine↗
PubMed2005

[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.

Animals↗
PubMed2004

[Anticholinergic Effect of a New Antiarrhythmic Class III Drug 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.

Action Potentials↗
PubMed2004

[Antiarrhythmic Efficacy of a New Class III Antiarrhythmic Drug RG-2.].

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.

Animals↗
PubMed2004

[The role of atrial pressure in spontaneous initiation of atrial fibrillation in the dog.].

Atrial fibrillation (AF) frequently occurred under conditions associated with atrial dilatation (stretch) or vagal hyperactivity. To study possible role of atrial stretch in spontaneous initiation of vagal AF we compared changes of right atrial pressure (RAP) and activation patterns during AF beginning. In anesthetized open-chest dogs (n=45) AF was induced by stimulation of vagal nerves (VS) (30-60 Hz, 5-10 s train). VS resulted in sinus node arrest (4.7+/-0.7 sec) with subsequent AF initiation in 153 of 229 cases. In 41% of cases of AF initiation the first atrial wave (A(1)) was closely related to ventricular activation (V) with V-A(1) interval of 94+/-5 ms (< > AF). This ventricular excitation induced acute short increase of RAP from 6.6.+/-0.6 to 12.9+/-1.1 mmHg (p<0.00l). Whereas other cases of AF initiation (59%) had no relation to ventricular activation (A(1)-V interval of 1382+/-173 ms) (< > AF). Atrial activation mapping (224 unipolar electrodes) showed that interval A(1)-A(2) of < > AF was significantly shorter than of < >. These data indicate that atrial stretch induced by elevation of RAP may facilitate the induction of AF but do not play a significant role in the mechanism of spontaneous AF initiation in this animal model.

Animals↗
PubMed2003

[Effects of verapamil on atrial fibrillation spontaneous initiation in the intact canine heart].

L-type Ca(2+) current (I(Ca,L)) has been shown to play a crucial role in initiation of early after depolarization (EAD) in cardiomyocytes. To study the possible role of EAD in spontaneous initiation of atrial fibrillation (AF), we tested the effects of L-type Ca(2+) channel blocker verapamil in canine models of cholinergic-dependent AF. In anesthetized open-chested dogs (n=13) spontaneous AF was induced by two methods: (1) perfusion with acetylcholine (ACh) in normal Tyrode solution at 9 ml/min into the sinus node artery (SNA) and (2) tonic stimulation of the right cervical vagus nerve (5 sec train). In the control, AF was induced in all dogs by perfusion with ACh (2.9+/-0.8 microM, mean+/-SEM) in 96+/-4% of attempts and by vagal stimulation (VS, 59+/-8 Hz) in 74+/-9% of attempts. Verapamil (0.2 mg/kg i.v.) did not alter the AF inducibility both during ACh perfusion and during VS (93+/-4% and 77+/-13%, NS, respectively) in dogs that retained sinus rhythm (n=8). However, verapamil significantly decreased AF inducibility to 50+/-4% and 21+/-13%, respectively, in dogs that passed to AV rhythm (n=5). Verapamil increased duration of both ACh- and vagally-mediated AF from 15+/-2 sec and 15+/-2 sec to 34+/-6 sec and 23+/-4 see (p<0.05 vs. control), respectively. The activation mapping (112 unipolar electrodes) during the initiation of AF did not reveal a difference in epicardial activation patterns before and after verapamil treatment. Inhibiting the I(Ca,L) by verapamil resulted in significant (p<0.05 vs. control) decrease in systolic and diastolic blood pressure, PQ interval prolongation and slowing down of the sinus rate. Verapamil did not affect atrial effective refractory period (AERP) and conduction velocity in the right atria. The reduction of AERP and the deceleration of heart rate by VS (8 Hz) remained unchangeable after verapamil treatment in comparison to control. Thus, the data suggest that the mechanism of spontaneous AF initiation during increased cholinergic activity is not related to EAD in atria.

Animals↗
PubMed2003

[Ionic mechanisms of cardiotropic action of a new class III antiarrhythmic drug 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.

Animals↗
PubMed2003

[Electrophysiological experimental study of a novel class III antiarrhythmic drug 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.

Animals↗
PubMed2002

[Effects of ryanodine receptors block on spontaneous initiation of atrial fibrillation in the intact canine heart].

To study the possible role of intracellular Ca2+ overload in initiation of cholinergic-dependent atrial fibrillation (AF), we tested the effects of ryanodine in canine models of AF. In anesthetized open-chest dogs (n=10) AF was induced by two methods: (I) perfusion (9 ml/min) with normal Tyrode solution containing acetylcholine (ACh) into the sinus node artery (SNA) and (II) stimulation of the right vagal nerve (VS, 5 sec train). AF was induced in all dogs: by perfusion with ACh (3.7-/+1.5 mcM) into the SNA in 97-/+3% of attempts and by VS in 78-/+6% of attempts. Intravenous infusion of ryanodine (5 mg/kg) did not prevent induction of AF during ACh perfusion (84-/+5%, NS) but completely prevented the induction of AF by VS (4-/+3%, p<0.001). Atrial activation mapping (112 unipolar electrodes) did not show any significant differences between the beginning of ACh-dependent AF in control and after ryanodine treatment. Ryanodine significantly reduced both systolic and diastolic arterial pressures but had no effect on heart rate, atrial effective refractory period (AERP) and conduction velocity for one hour after infusion. Ryanodine, itself, did not exert antivagal activity, so after ryanodine treatment in the presence of VS (8 Hz) the reduction of AERP and the deceleration of heart rate were similar to that in control. These data suggest that ryanodine can suppress the initiation of AF induced by VS but not AF induced by ACh perfusion. We can conclude that the initiation of AF during ACh perfusion unlikely relates to triggering activity induced by intracellular Ca2+ overload. In addition, we suggest that besides ACh some 'unclear' ryanodine sensitive factor(s) contribute to the initiation of AF induced by VS.

Animals↗
PubMed2001

[Trigger activity of ryanodine in mechanism of cholinergic atrial fibrillation in dogs].

Systemic infusion of ryanodine did not prevent induction of atrial fibrillation (AF) during acetylcholine (Ach) perfusion in frogs. The AF, however, appeared later as of the dogs/Ach perfusion start and lasted for a shorter time as compared with the control. The activation mapping of the right atrium showed no significant difference from the control. The findings suggest that the mechanism of AF induction is hardly related to triggering activity, at least in this particular model.

Acetylcholine↗
PubMed2001

[Isoproterenol potentiates atrial fibrillation induced by acetylcholine].

A perfusion with normal Tirode solution containing isoproterenol, acetylcholine and their combination into the sinus node artery of the anesthetized open-chest dogs was used to induce atrial fibrillation. The perfusion of isoproterenol, alone, was unable to induce atrial fibrillation, though significantly increased atrial rate. Meanwhile the perfusion of acetylcholine, alone, did induce atrial fibrillation in all animals. The mixed perfusion of isoproterenol and acetylcholine led to decreasing the threshold (minimum) concentration of acetylcholine to induce atrial fibrillation. Herewith, atrial fibrillation appeared at later time from a perfusion start and lasted for more long time. No significant slowing down of sinus rhythm was registered before the initiation of atrial fibrillation. The data suggest that initiation of paroxysmal atrial fibrillation may only be mediated by parasympathetic activity and dependents on a level of adrenergic activity.

Acetylcholine↗
PubMed1999

[The cholinolytic activity of the new anti-arrhythmia preparation Nibentan].

In the rabbit isolated right atrium and the rat atrial cells, a new class III antiarrhythmic drug Nibentan was shown to exert an anticholinergic effect contrary to Carbachol: the latter decreased the AP duration to 42 +/- 2% of the control whereas Nibentan restored it to 65 +/- 2%. The anticholinergic effect of the drug was found to be due to inhibition of the acetylcholine-activated potassium current: it was decreased by 79 +/- 3% in the rat isolated single atrial cells. In the rabbit isolated sino-atrial node, Nibentan prevented arrhythmogenic effects of vagal stimulation. The new drug may be quite efficient in treatment of flutter and atrial fibrillation.

Action Potentials↗
PubMed1999

[Asymmetric responses of epicardial and endocardial fibers of the dog atrium to cholinergic effects].

The ACh shortened the AP in canine epicardial and endocardial cells, the effect being more obvious in the latter. The findings suggest that 4-aminophyridine-sensitive transient outward current is expressed in canine atrial epicardial and endocardial cells, that the ACh exerts direct effects on epicardial and endocardial AP duration, that differential responses of epicardial and endocardial AP duration to the ACh may alter the gradient of repolarisation across the atrial wall and contribute to the vagus-indoced atrial flutter and fibrillation.

Acetylcholine↗
PubMed1998

[Comparison of atrial premature depolarization topography during vagal stimulation and humoral acetylcholine administration].

Epicardial atrial mapping in open-chest dogs during different cholinergic influences has shown that, in acetylcholine administration and vagal stimulation, spatial distribution of atrial premature depolarisation (APDs) seems to be similar to prevalence of ectopic sources from both atria and atrial septum. Spatial distribution of the APDs in acetylcholine administration in the sinus node artery was limited to the region of this artery so that the APDs mainly arise from intercaval area of the right atrium and from atrial septum, but never from the left atrium. The latent pacemakers spread over both atria and atrial septum, could participate in initiation of cholinergically-induced APDs and atrial fibrillation. A direct effect of acetylcholine seems to be necessary for development of arrhythmic activity of the latent pacemakers.

Acetylcholine↗
PubMed1998

[The role of the interatrial septum in development of supraventricular tachyarrhythmias of vagal origin in dogs].

Patterns of atrial activation of ectopic pulse source during vagal stimulation were studied on atrial epicardial surface and atrial septum in mongrel dogs. Epicardial activation maps were drafted. The findings show that, irrespective of preferred direction of conduction in the atria and septum, the entire atrial myocardium acted as a conducting system. Mapping of the first extrasystolic beats during tachyarrhythmias induced with vagal stimulation, has shown their ectopic origin. The data obtained confirms the suggestion that atrial fibrillation may be due to a single source of arrhythmia in septal area.

Animals↗
PubMed1998

[The first original Russian class-III antiarrhythmic nibentan].

The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.

Animals↗