Passive current redistribution in the heart.
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Electric Conductivity↗
Biomedical subjects
T Mazgalev
Publications and source records attributed to T Mazgalev.
Virtual electrode-induced phase singularity: a basic mechanism of defibrillation failure.
Delivery of a strong electric shock to the heart remains the only effective therapy against ventricular fibrillation. Despite significant improvements in implantable cardioverter defibrillator (ICD) therapy, the fundamental mechanisms of defibrillation remain poorly understood. We have recently demonstrated that a monophasic defibrillation shock produces a highly nonuniform epicardial polarization pattern, referred to as a virtual electrode pattern (VEP). The VEP consists of large adjacent areas of strong positive and negative polarization. We sought to determine whether the VEP may be responsible for defibrillation failure by creating dispersion of postshock repolarization and reentry. Truncated exponential biphasic and monophasic shocks were delivered from a bipolar ICD lead in Langendorff-perfused rabbit hearts. Epicardial electrical activity was mapped during and after defibrillation shocks and shocks applied at the plateau phase of a normal action potential produced by ventricular pacing. A high-resolution fluorescence mapping system with 256 recording sites and a voltage-sensitive dye were used. Biphasic shocks with a weak second phase (<20% leading-edge voltage of the second phase with respect to the leading-edge voltage of the first phase) produced VEPs similar to monophasic shocks. Biphasic shocks with a strong second phase (>70%) produced VEPs of reversed polarity. Both of these waveforms resulted in extra beats and arrhythmias. However, biphasic waveforms with intermediate second-phase voltages (20% to 70% of first-phase voltage) produced no VEP, because of an asymmetric reversal of the first-phase polarization. Therefore, there was no substrate for postshock dispersion of repolarization. Shocks producing strong VEPs resulted in postshock reentrant arrhythmias via a mechanism of phase singularity. Points of phase singularity were created by the shock in the intersection of areas of positive, negative, and no polarization, which were set by the shock to excited, excitable, and refractory states, respectively. Shock-induced VEPs may reinduce arrhythmias via a phase-singularity mechanism. Strong shocks may overcome the preshock electrical activity and create phase singularities, regardless of the preshock phase distribution. Optimal defibrillation waveforms did not produce VEPs because of an asymmetric effect of phase reversal on membrane polarization.
Animals↗
Iridium oxide-coated defibrillation electrode: reduced shock polarization and improved defibrillation efficacy.
BACKGROUND: Transvenous implantable cardioverter-defibrillator (ICD) leads are designed to deliver electric shocks to the heart for termination of ventricular dysrhythmias. However, the efficiency of different lead materials has not been well studied. This study compares an ICD lead coated with iridium oxide (IROX), a material that reduces shock-induced polarization, with an otherwise identical, uncoated lead. METHODS AND RESULTS: The defibrillation threshold (DFT) was determined in 13 swine with both IROX-coated and uncoated ICD leads paired with an uncoated "can" electrode. The leads were exchanged through a Teflon sheath to reproduce the intracardiac position. The delivered energy DFT of the IROX-coated lead was 15.9+/-5.4 J and was significantly lower than the delivered energy DFT of the uncoated lead (19.1+/-5.1 J; P<.006). The initial lead impedance was equivalent in both leads (IROX, 41.7+/-5.8 omega; uncoated, 41.3+/-4.7 omega; P=NS) at DFT. However, the impedance rose by 7.3+/-2.0 omega during the first phase and by 3.7+/-2 omega during the second phase with the uncoated lead, whereas the corresponding impedance change was 1.0+/-0.3 omega during phase 1 and 1.6+/-0.5 omega during phase 2 (P<.01 each phase) when the IROX-coated lead was used. CONCLUSIONS: This study shows that an IROX coating of this lead system significantly lowers the DFT energy in the swine model. The blunting of the impedance rise by the IROX coating that is seen is consistent with a reduction in electrode polarization.
Animals↗
Mechanism of atrioventricular nodal facilitation in the rabbit heart: role of the distal AV node.
We investigated whether atrioventricular (AV) nodal facilitation is the result of distal AV nodal action potential shortening. Atrial and bundle of His (H) electrograms and microelectrode recordings from proximal and distal AV nodal cells were analyzed in eight superfused rabbit AV node preparations in response to two pacing protocols. In the facilitation protocol, an atrial extrastimulus (A3) was preceded by an atrial impulse (A2) introduced 300, 200, 150, or 125 ms after 30 basic beats (A1). The preexcitation protocol differed from the facilitation protocol by the addition of a premature His depolarization (h2) such that the H1-h2 interval was shorter than the H1-H2 interval. Conduction curves (A3-H3 vs. H2-A3, h2-A3, and A2-A3 intervals) were constructed. Facilitation was demonstrated in all preparations when H2-A3 was used (P = 0.02) but not in the A2-A3 format. Compared with facilitation at the same A1-A2 intervals, preexcitation, despite shortening the distal cellular action potential duration, resulted in longer A3-H3 delays (P = 0.002), shorter A2-A3 intervals, and depression of the proximal nodal cellular response. Thus facilitation does not result from altered distal AV nodal characteristics and instead is a manifestation of an uncontrolled pacing protocol-dependent modulation of proximal AV nodal function.
Action Potentials↗
Mechanism of atrioventricular nodal facilitation in rabbit heart: role of proximal AV node.
The phenomenon of atrioventricular (AV) nodal "facilitation," described in traditional "black box"-functional studies, implies enhanced AV nodal dromotropic function. We investigated the role of atrial prematurities in the modulation of the nodal cellular responses in the mechanism of AV nodal facilitation. Atrial and His (H) bundle electrograms and microelectrode recordings from proximal AV nodal cells were analyzed in 15 superfused rabbit AV node preparations. The pacing protocol consisted of 30 basic beats (S1; coupling interval S1-S1 = 300 ms) followed by a facilitating prematurity (S2; coupling intervals S1-S2 of 300, 200, 150, and 130 ms) followed by the test beat (S3; coupling interval S2-S3 scanned in 5-ms steps). Conduction curves (S2-H2 vs. S1-S2, S3-H3 vs. S2-S3, and S3-H3 vs. H2-S3) were constructed. Facilitation (i.e., shortening of S3-H3 when S1-S2 was shortened) was demonstrated in all preparations using the H2-S3 (P < 0.001) but not the S2-S3 format. Microelectrode recordings revealed a causal relationship between the improved proximal AV nodal cellular responses in facilitation and the prolonged S2-S3 interval. There was no evidence for enhanced nodal dromotropic function directly resulting from the introduction of the facilitating beats. Thus facilitation is based on inherent cycle-length-dependent properties of the AV node during application of a complex pacing protocol and primarily reflects the uncontrolled modulation of the proximal cellular response.
Animals↗
Atrioventricular nodal conduction gap and dual pathway electrophysiology.
BACKGROUND: The gap phenomenon in atrioventricular (AV) conduction is described as a block that occurs within a range of atrial coupling intervals. This block is assumed to occur between two adjacent parts of the conduction system having different refractory properties; thus, a gap would develop if the functional refractory period of the proximal unit was shorter than the effective refractory period of the distal unit. We describe a new electrophysiological mechanism based on dual pathways electrophysiology of the AV node. METHODS AND RESULTS: In vitro experiments were performed on isolated superfused rabbit hearts. Standard electrophysiological pacing and recording techniques were used to generate conduction curves. The gap phenomenon was documented in 9 of 14 nodal preparations. With shortening of the atrial coupling interval, antegrade conduction block of the "fast" pathway wave front occurred while this impulse was still retrogradely interfering with slow pathway conduction. That is, the fast pathway wave front prevented propagation of the anterograde "slow" pathway wave front by collision or by creating a refractory barrier. This mechanism produced a gap and the block persisted until, at even shorter coupling intervals, the fast wave front penetration became insufficient and conduction was restored through the released slow pathway wave front. This mechanism was verified in AV nodal preparations with separated inputs, in which independent fast and slow wave fronts could be induced and programmed to collide. CONCLUSIONS: Our results established the functional interaction of fast and slow pathway wave fronts as an important electrophysiological mechanism underlying the AV conduction gap. This mechanism may be responsible for a variety of clinically observed conduction discontinuities.
Animals↗
Asymmetry of retrograde conduction and reentry within the His-Purkinje system: a comparative analysis of left and right ventricular stimulation.
OBJECTIVES: The purpose of this study was to delineate retrograde His-Purkinje system conduction and reentry (V3 phenomenon) during left ventricular extrastimulation and compare them with right ventricular extrastimulation. BACKGROUND: The V3 phenomenon has been well described in the past during right ventricular extrastimulation; however, it has not been studied systematically during left ventricular extrastimulation. METHODS: Left and right ventricular pacing were performed in 13 patients. Retrograde and anterograde routes of impulse propagation were determined on the basis of the sequence of His (H) and right bundle (RB) potentials, H-RB intervals, as well as the QRS configuration and axis of V3 beats. RESULTS: During right ventricular pacing, retrograde conduction of V2, when discernible, occurred exclusively through the left bundle at all coupling intervals equal to or shorter than the His-Purkinje relative refractory period, with the exception of two isolated beats. During left ventricular extrastimulation, His bundle activation was through the left bundle in nine patients and through the right or left bundle in three other patients. In one patient, the route could not be determined. The V3 phenomena occurred in eight patients during right ventricular pacing. Seven patients had a left bundle branch block pattern QRS configuration, and one had a right bundle branch block pattern configuration. V3 beats occurred in five patients during left ventricular apex pacing: left bundle branch block pattern configuration in one patient and right bundle branch block pattern configuration in four. In three of these four patients, the reentry was interfascicular and limited to the left bundle branch system. CONCLUSIONS: The left-sided His-Purkinje system is the preferred retrograde route of impulse propagation during both left and right ventricular extrastimulation. Reentry within the His-Purkinje system elicited by right ventricular extrastimulation involves both bundle branches, whereas this reentry tends to occur within the left-sided His-Purkinje system during left ventricular pacing.
Adolescent↗
Morphological and electrophysiological correlates of atrioventricular nodal response to increased vagal activity.
The mechanisms responsible for slowing cardiac impulse conduction through the atrioventricular (AV) node are not well understood but include anatomical architecture, presence of cells with diverse electrophysiological characteristics, and modulation by autonomic nervous system. The present study was designed to determine the site of vagally induced slowing of conduction through the AV node. We attempted to correlate the electrophysiological response of AV nodal cells to postganglionic vagal stimulation applied in different regions of the node with the morphological findings and patterns of acetylcholinesterase-positive staining of nodal tissue. This multifaceted approach revealed that vagal stimulation produced localized hyperpolarization of the cells from the N region of the AV node, which correlated with the strong acetylcholinesterase positive staining of the central nodal area. In contrast, the density of the acetylcholinesterase staining decreased toward both the AN and His bundle regions, whereas vagal stimulation had a negligible effect on the cells from these regions. These results suggest that vagal-induced depression of AV nodal conduction is produced by release of acetylcholine predominantly around the midnodal region and the depressive action of acetylcholine is concentrated on the cells occupying the same region (i.e., the N cells). Thus, there appears to be a close juxtaposition of nerve elements and effector cells in the midnodal region of the AV node. This unique combination of available neuromediator and responding cells with hyperpolarization and depressed action potential determines the midnodal region as the focus of vagal effect on AV nodal conduction.
Animals↗
A new mechanism for atrioventricular nodal gap-vagal modulation of conduction.
The well-known paradoxic behavior of atrioventricular conduction, the so-called gap phenomenon, that occurs when impulses within a certain range of coupling intervals are blocked while impulses with shorter coupling intervals are conducted is attributed to differences in properties of refractoriness in neighboring regions of the conduction system. In contrast, in the present study a model was developed showing a similar phenomenon, dependent on different electrophysiologic mechanisms and localized within the atrioventricular node in an isolated rabbit heart tissue preparation (n = 11). The hearts were paced at cycle length of 400-500 msec, and atrioventricular nodal conduction times (A2H2) were measured versus atrial extrastimulus (A1A2) coupling intervals by standard extrastimulus techniques. Postganglionic vagal stimulation was applied in the atrioventricular node as short bursts of subthreshold (for myocardium) stimuli with duration of 50-150 msec, amplitude of 20-800 microA, and absolute phase (delay after A1) of 0-500 msec. Vagal bursts with appropriate parameters consistently produced bimodal conduction curves. Initially, gradual shortening of the A1A2 coupling interval was associated with an increasing A2H2, with an accentuated increase (or even atrioventricular block) within an intermediate A1A2 range. However, further shortening of the A1A2 coupling interval produced a decrease in A2H2, which subsequently was followed by a block at the effective refractory period. Microelectrode recordings indicated that this characteristic bimodal pattern of conduction curves, demonstrating a gap, reflected transient vagally induced hyperpolarization in the N region of the node. In those instances where conduction block occurred and gap was manifest, the most marked hyperpolarization coincided with the time of arrival of midcycle premature extrastimuli, whereas the conduction of extrastimuli with either more or less prematurity was under less-marked vagal influence. Thus, this study demonstrates a new electrophysiologic mechanism producing anomalous conduction curves and the gap phenomenon within the atrioventricular node based on vagal-induced nonuniform recovery of diastolic excitability.
Animals↗
"Atrial paralysis": does it explain the irregular ventricular rate during atrial fibrillation?
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Atrial Fibrillation↗
Interacting negative chronotropic effects of adenosine and the vagus nerve on the canine sinus node.
The vagus nerve and adenosine exert a negative chronotropic effect on the mammalian sinus node. In addition, adenosine is released from myocardial cells under both physiological and pathophysiological conditions, which are characterised by variable vagal tone. To determine the interaction between adenosine and the vagus nerve, 21 barbiturate anaesthetised mongrel dogs with bilateral cervical vagotomy and stellectomy were studied. In group 1 (n = 16) adenosine (3 mumol.kg-1) was rapidly (less than or equal to 1 s) administered before (control) and during 60 s of repetitive vagal stimulation. Each stimulus (consisting of a burst of 5 square wave pulses, 0.3 mA in amplitude and 1 ms in duration at 0.1 kHz) was given at a fixed point in time in each sinus cycle (that is, one burst per cycle). This protocol was repeated after a 50 ms incremental change in the phase at which vagal stimulation was given until the entire cycle length was scanned. Recovery time of at least 2 min separated any two consecutive adenosine administrations. In four animals the above protocol was performed twice using vagal stimulation amplitude of 0.3 mA and 0.6 mA in the first and second runs respectively. In this group (group 1), the effect of adenosine was altered by the vagus in a phase dependent manner. In each animal, however, there was at least one phase of the sinus cycle during which vagal stimulation significantly enhanced the effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine↗
Vagal control of the atrioventricular node--in vitro observations. I. Electrophysiological mechanism underlying the effects of brief vagal discharges on atrioventricular nodal conduction.
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Acetylcholine↗
Vagal control of the atrioventricular node--in vitro observations. II. Differential postganglionic vagal influence on anterograde atrioventricular nodal conduction and junctional pacemaker activity.
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Animals↗
Modulation of the effects of postganglionic vagal stimulation in the sinus and atrioventricular nodes by cardioactive agents and electrolytes.
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Adenosine↗
Differential vagal effects on antegrade vs. retrograde atrioventricular conduction.
The influence of postganglionic vagal stimulation (PGVS) on antegrade and retrograde atrioventricular nodal conduction was studied in 17 isolated rabbit heart tissue preparations by pacing at the crista terminalis or His bundle, respectively. The effect of short bursts of PGVS on prolongation of atrioventricular conduction was phase dependent with respect to the cardiac cycle. This phasic dependency was more pronounced during antegrade atrioventricular conduction. Although the control retrograde atrioventricular conduction time was longer than the antegrade (P less than 0.05) at or near the time in the cycle during which vagal stimulation caused maximal prolongation of conduction time (optimal phase), PGVS-induced maximal prolongation of the antegrade atrioventricular conduction time was significantly greater than that of the retrograde (P less than 0.02). Moreover, when PGVS was introduced at a fixed phase in the cycle, but with increasing amplitude, antegrade atrioventricular conduction time was progressively prolonged, and block was observed first in the antegrade direction, whereas retrograde atrioventricular conduction continued. Microelectrode recordings during these experiments showed consistently that PGVS-induced hyperpolarization in the N region of the atrioventricular node was greater during antegrade atrioventricular conduction. This suggests that vagal effects depended not only on the intensity and phase of stimulation, but also on electronic influences which apparently are different during antegrade and retrograde conduction.
Action Potentials↗
Adenosine-vagus interaction at the cellular level.
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Adenosine↗
Interactive negative chronotropic actions of adenosine and verapamil on the canine sinus node in vivo.
To study the interaction between adenosine and verapamil, adenosine (3 mumol/kg) was administered rapidly into the right atrium before and following verapamil (0.2 mg/kg, i.v.) in 25 pentobarbital anesthetized dogs divided into 4 groups: I (n = 7) - intact dogs; II (n = 6) - dogs pretreated with atropine (0.2 mg/kg, i.v.); III (n = 6) - dogs pretreated with propranolol (1 mg/kg, i.v.) and IV (n = 6) - bilateral stellectomized and cervical vagotomized dogs. Arterial blood pressure, standard lead II ECG, as well as right atrial, right ventricular and His bundle electrograms were continuously monitored and recorded. The negative chronotropic effect of adenosine was determined as the maximal prolongation in sinus cycle length (SCL). Verapamil maximally prolonged SCL by 70 +/- 14 msec (p less than 0.005) in Group I, 39 +/- 15 msec (0.1 greater than p greater than 0.005) in Group II, 86 +/- 18 msec (p less than 0.01) in Group III and by 100 +/- 12 msec (p less than 0.001) in Group IV. In Group I, control dogs, adenosine increased SCL by 82 +/- 21 msec before vs. 185 +/- 35 msec 15 minutes after verapamil, respectively (p less than 0.05). This potentiating effect of verapamil was completely abolished by atropine and markedly attenuated by propranolol. In stellectomized + vagotomized dogs, adenosine-verapamil interaction was more complex. In this group adenosine prolonged sinus cycle length maximally by 270 +/- 41 msec before verapamil, but following verapamil this effect of adenosine was transiently attenuated with a maximal sinus cycle length prolongation of only 165 +/- 24 msec (10 minutes following verapamil) (p less than 0.05, vs. before verapamil). These data indicate that the autonomic nervous system modulate the interactive negative chronotropic effects of adenosine and verapamil in the canine sinus node. Hence, the adenosine-verapamil interaction has clinical implications for conditions in which release of adenosine is increased (e.g. myocardial ischemia) or adenosine is administered in the presence of verapamil.
Adenosine↗
Vagal component in the chronotropic and dromotropic actions of adenosine and ATP.
Several studies indicate that the vagus plays an important modulating role in the electrophysiologic actions of exogenous adenosine and ATP in the heart of certain mammalian species. In addition, extracellular adenosine can enhance the depressant effects of the vagus on the heart. These findings have immediate clinical implication with regard to the use of adenosine and ATP as antiarrhythmic agents as well as the mechanism of cardiac arrhythmias associated with high vagal tone and/or elevate extracellular adenosine levels.
Adenosine↗