Atrial Refractory Period Research Articles

Premature ventricular contractions causing pacemaker-mediated tachycardia: A failure of postventricular atrial refractory period after premature ventricular contraction extension?

Premature ventricular contractions causing pacemaker-mediated tachycardia: A failure of postventricular atrial refractory period after premature ventricular contraction extension?

Pathophysiology and Treatment Strategy for Atrial Fibrillation In Patients with Impaired LV Function

A variety of pathophysiological factors contribute to the development of atrial fibrillation in heart failure. More specifically, the elevated left atrial pressure, stretching and dilatation of atrial muscle, activation of the sympathetic nervous system and neurohumoral factors, atrial muscle hypertrophy, ischemia, fibrosis, etc., associated with impaired left ventricular function promote electrophysiological changes, such as shortening of atrial refractory period, and conduction disorders, leading to reentrant tachyarrhythmias.

In Vivo Cardiac Electrophysiologic Effects of a Novel Diphenylphosphine Oxide IKur Blocker, (2-Isopropyl-5-methylcyclohexyl) Diphenylphosphine Oxide, in Rat and Nonhuman Primate

The voltage-gated potassium channel, Kv1.5, which underlies the ultrarapid delayed rectifier current, I(Kur), is reported to be enriched in human atrium versus ventricle, and has been proposed as a target for novel atrial antiarrhythmic therapy. The administration of the novel I(Kur) blocker (2-isopropyl-5-methyl-cyclohexyl) diphenylphosphine oxide (DPO-1) (0.06, 0.2, and 0.6 mg/kg/min i.v. x 20 min; total doses 1.2, 4.0, and 12.0 mg/kg, respectively) to rat, which exhibits I(Kur) in both atria and ventricle, elicited significant, dose-dependent increases in atrial and ventricular refractory period (9-42%) at all doses tested, with no changes in cardiac rate or indices of cardiac conduction. Plasma levels achieved in rat at the end of the three infusions were 1.1, 4.1, and 7.7 microM. Reverse transcription-polymerase chain reaction analysis of African green monkey atria and ventricle demonstrated an atrial preferential distribution of Kv1.5 transcript. The administration of DPO-1 (1.0, 3.0, and 10.0 mg/kg i.v.; 5-min infusions) to African green monkey elicited significant increases in atrial refractoriness (approximately 15% increase at the 10.0 mg/kg dose), with no change in ventricular refractory period, ECG intervals, heart rate, or blood pressure. Plasma levels of DPO-1 achieved in African green monkey were 0.58, 1.12, and 5.43 microM. The concordance of effect of DPO-1 on myocardial refractoriness with distribution of Kv1.5 in these two species is consistent with the I(Kur) selectivity of DPO-1 in vivo. Moreover, the selective increase in atrial refractoriness in primate supports the concept of I(Kur) blockade as an approach for the development of atrial-specific antiarrhythmic agents.

Dietary Fish Oil Protects Against Stretch‐Induced Vulnerability to Atrial Fibrillation in a Rabbit Model

Dietary fish oil is thought to reduce sudden cardiac death by suppressing ventricular arrhythmias but little is known about its impact on atrial arrhythmias. We examined the effect of dietary fish oil on the rabbit model of stretch-induced vulnerability to atrial fibrillation (AF). Six-week-old rabbits were fed standard rabbit pellets supplemented with 5% tuna fish oil (n = 6) or supplemented with 5% sunflower oil (n = 6) for 12 weeks. Six rabbits raised on the standard diet were used as controls. In Langendorff-perfused hearts intraatrial pressures were increased in a stepwise manner and rapid burst pacing applied to induce AF at increasing intraatrial pressures until AF was sustained (>1 minute). Atrial refractory periods were recorded at each pressure. Increased atrial pressure resulted in a reduction in atrial refractory period and a propensity for induction of sustained AF. Higher pressures were needed to induce and sustain AF in the fish oil group compared with the sunflower oil and control groups. The stretch-induced drop in refractory period was also less marked in the fish oil group. Red blood cell, atrial, and ventricular omega-3 fatty acid levels were significantly higher in the fish oil group. The ratio of atrial n-6/n-3 polyunsaturated fatty acids was 13 +/- 0.9 with sunflower oil and 1.5 +/- 0.01 with fish oil (P < 0.001). Incorporation of dietary omega-3 fatty acids into atrial tissue reduces stretch-induced susceptibility to AF.

Mode Switching of Dual Chamber Pacemakers from Activation of a Blanked Flutter Search Algorithm by a Single Atrial Event

The Medtronic Kappa 700 and 900 pacemaker family offers a dedicated Blanked Flutter Search algorithm specifically designed for the detection of atrial flutter. This report describes 5 cases that demonstrate how the Blanked Flutter Search algorithm can be activated in the absence of atrial tachycardia, atrial flutter, or sinus tachycardia by a single atrial event (AR) detected in the atrial refractory period of the pacemaker provided it is either preceded or followed by a sensed atrial event (AS).

Wide complex tachycardia and dual-chamber pacing

76-year-old man with a history of cardiomyopathy, ventriclar tachycardia (VT), severe heart failure, and electrical dysynchrony (QRS duration 180 ms) underwent upgrading of an xisting device to a cardiac resynchronization defibrillator. The eft ventricular lead subsequently was removed because of uboptimal lead parameters. The generator (model V-340), the ight ventricular (RV) lead (model 1559), and the atrial lead model 1488T) were manufactured by St. Jude Medical (Sylar, CA, USA). The device was programmed to DDD pacing t base rate of 95 bpm and upper tracking rate of 120 bpm for etter hemodynamic response. Other parameters were prorammed as follows: paced and sensed AV delay 180 and 160 s, respectively, postventricular atrial refractory period 310 s, ventricular refractory period 220 ms, atrial sensitivity 1.0 V, ventricular sensitivity automatic (maximum 0.3 mV), and acing outputs in A and V of 4.0 V and 5.0 V at 0.5-ms pulse idth, respectively. The detection rates for VT and ventricular brillation were programmed at 430 ms (140 bpm) and 330 ms 182 bpm), respectively. Postoperatively, a stable wide comlex rhythm at 95 bpm with intermittent pacing spikes was bserved. The device was interrogated during such an episode Figure 1). What is the arrhythmia? What is the mechanism of ntermittent pacing? Is it malfunctioning of the device?

Developmental Changes in Sinus Node Function in Growing Children: An Updated Analysis

Sinus node dysfunction (SAND) may be congenital or acquired following injury or surgery for congenital heart lesions. Sinus node function is evaluated by electrophysiological (EP) parameters of corrected sinus node recovery time (CSNRT) and sinoatrial conduction time (SACT). The aim of this study was to determine age- and gender-specific values for CSNRT and SACT in pediatric patients without structural congenital heart disease. Data were collected on 152 patients who underwent an EP study for evaluation of supraventricular tachycardia between 1997 and 2002. All patients received midazolam and propofol and/or isoflurane for sedation and anesthesia, which are known to not affect EP parameters. The age of transition at which CSNRT changed significantly was 14 years (241.5 +/- 102.0 msec in patients younger than 14 years old and 285.6 +/- 144.3 msec in those older than 14 years, p < 0.05). The upper limits of normal CSNRT (mean + 2 SD) were significantly higher (445 vs 275 msec) and the upper limits of normal SACT values were lower (120 vs 200 msec) than the currently used norms in the younger age group. CSNRT values and atrial refractory period values were significantly longer in males compared to age-matched females [278.5 +/- 15.3 VS : 236.4 +/- 13.6 msec (p < 0.05) and 269.0 +/- 4.9 VS: 244.7 +/- 6.8 msec (p < 0.005), respectively]. The new age- and gender-specific values of EP parameters, which reflect sinus node function, may enable more precise recognition of SAND.

Cross‐Ventricular Pacemaker‐Mediated Tachycardia by Myopotential Induction during Biventricular Pacing

Patients in permanent atrial fibrillation treated for heart failure and ventricular asynchrony can be implanted with conventional dual chamber pacemakers (DDD) pacemakers used in the biventricular mode. The left ventricular lead is connected to the atrial channel. We report the case of a patient who developed ventriculo-ventricular pacemaker-mediated tachycardia (PMT) induced by myopotential sensing in the atrial channel, inhibiting left ventricular pacing. In the absence of specifically designed pacemakers, the use of DDD pacemakers in the biventricular mode requires certain precautions, such as anti-PMT mode activation, disabling automatic sensitivity, and lengthening the postventricular atrial refractory period (PVARP), or mode switch to DVIR.

181 A device based automatic post ventricular atrial refractory period (PVARP) algorithm

181 A device based automatic post ventricular atrial refractory period (PVARP) algorithm

181 A device based automatic post ventricular atrial refractory period (PVARP) algorithm

181 A device based automatic post ventricular atrial refractory period (PVARP) algorithm

Short QT Syndrome and Atrial Fibrillation Caused by Mutation in KCNH2

The short QT syndrome is a newly described clinical entity characterized by the presence of a short QT interval associated with cardiac tachyarrhythmias including sudden cardiac death at a young age in otherwise healthy individuals. A genetic basis has been identified linking the disease to mutations in KCNH2 in the familial forms and a mutation in KCNQ1 in a sporadic form of the disease. We identified a family with short QT syndrome with a high incidence of paroxysmal atrial fibrillation in their members and no known history of sudden cardiac death. QT interval ranged from 225 to 240 ms within normal heart rate ranges in the affected individuals. Programmed electrical stimulation (PES) was performed in all affected members, which revealed a remarkably short atrial and ventricular refractory period, and inducibility of atrial and ventricular fibrillation. Treatment with propafenone has maintained the individuals free of atrial fibrillation to date. Genetic analysis identified a missense mutation (C to G substitution at nucleotide 1764) which resulted in the amino acid change (N588K) in KCNH2. This mutation had been previously described in two other families with a high incidence of sudden cardiac death. Our study confirms that N588K is a hotspot for familial form of the short QT syndrome. The disease is clinically heterogeneous, as indicated by the fact that, in the three families with the same mutation, there is a wide range of symptoms, varying from atrial to ventricular fibrillation and sudden death. While the implantation of a defibrillator appears warranted due to the inducibility at PES, the clinical follow-up provides indication that the class Ic agent propafenone could be effective to prevent episodes of paroxysmal atrial fibrillation.

Electrocardiographic Follow‐Up of Biventricular Pacemakers

Multisite pacing for the treatment of heart failure has added a new dimension to the electrocardiographic evaluation of device function. During left ventricular (LV) pacing from the appropriate site in the coronary venous system, a correctly positioned lead V1 registers a right bundle branch block pattern with few exceptions. During biventricular stimulation associated with right ventricular (RV) apical pacing, the QRS is often positive in lead V1. The frontal plane QRS axis is usually in the right superior quadrant and occasionally in the left superior quadrant. Barring incorrect placement of lead V1 (too high on the chest), lack of LV capture, LV lead displacement or marked latency (exit block or delay from the stimulation site), ventricular fusion with the spontaneous QRS complex, a negative QRS complex in lead V1 during biventricular pacing involving the RV apex probably reflects different activation of an heterogeneous biventricular substrate (ischemia, scar, His-Purkinje participation in view of the varying patterns of LV activation in spontaneous left bundle branch block) and does not necessarily indicate a poor (electrical or mechanical) contribution from LV stimulation. In this situation, it is imperative to rule out the presence of coronary venous pacing via the middle cardiac vein or even unintended placement of two leads in the RV. During biventricular pacing with the RV lead in the outflow tract, the paced QRS in lead V1 is often negative and the frontal plane paced QRS axis is often directed to the right inferior quadrant (right axis deviation). In patients with sinus rhythm and a relatively short PR interval, ventricular fusion with competing native conduction during biventricular pacing may cause misinterpretation of the ECG because narrowing of the paced QRS complex simulates appropriate biventricular capture. This represents a common pitfall in device follow-up. Elimination of ventricular fusion by shortening the AV delay, is often associated with clinical improvement. Anodal stimulation may complicate threshold testing and should not be misinterpreted as pacemaker malfunction. One must be cognizant of the various disturbances that can disrupt 1:1 atrial tracking and cause loss of ventricular resynchronization. (1) Upper rate response. The upper rate response of biventricular pacemakers differs from the traditional Wenckebach upper rate response of conventional antibradycardia pacemakers because heart failure patients generally do not have sinus bradycardia or AV junctional conduction delay. The programmed upper rate should be sufficiently fast to avoid loss of resynchronization in situations associated with sinus tachycardia. (2) Below the programmed upper rate. This may be caused by a variety of events (especially ventricular premature complexes and favored by the presence of first-degree AV block) that alter the timing of sensed and paced events. In such cases, atrial events become trapped into the postventricular atrial refractory period at atrial rates below the programmed upper rate in the presence of spontaneous AV conduction. Algorithms are available to restore resynchronization by automatic temporary abbreviation of the postventricular atrial refractory period.

Origin and pharmacological response of atrial tachyarrhythmias induced by activation of mediastinal nerves in canines

We sought to determine the sites of origin of atrial tachyarrhythmias induced by activating mediastinal nerves, as well as the response of such arrhythmias to autonomic modulation. Under general anaesthesia, atrioventricular block was induced after thoracotomy in 19 canines. Brief trains of 5 electrical stimuli were delivered to right-sided mediastinal nerves during the atrial refractory period. Unipolar electrograms were recorded from 191 right and left atrial epicardial sites under several conditions, i.e. (i) with intact nervous systems and following (ii) acute decentralization of the intrathoracic nervous system or administration of (iii) atropine, (iv) timolol, (v) hexamethonium. Concomitant right atrial endocardial mapping was performed in 7 of these dogs. Mediastinal nerve stimulation consistently initiated bradycardia followed by atrial tachyarrhythmias. In the initial tachyarrhythmia beats, early epicardial breakthroughs were identified in the right atrial free wall (28/50 episodes) or Bachmann bundle region (22/50), which corresponded to endocardial sites of origin associated with the right atrial subsidiary pacemaker complex, i.e. the crista terminalis and dorsal locations including the right atrial aspect of the interatrial septum. Neuronally induced responses were eliminated by atropine, modified by timolol and unaffected by acute neuronal decentralization. After hexamethonium, responses to extra-pericardial but not intra-pericardial nerve stimulation were eliminated. It is concluded that concomitant activation of cholinergic and adrenergic efferent intrinsic cardiac neurons induced by right-sided efferent neuronal stimulation initiates atrial tachyarrhythmias that originate from foci anatomically related to the right atrial pacemaker complex and tissues underlying major atrial ganglionated plexuses.

Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation

Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post-repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. In 12 patients with persistent AF (11 male, 58 +/- 5 yrs, 27 +/- 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. Both drugs prolonged APD90 during AF (flecainide from 109 +/- 7 ms to 137 +/- 10 ms, sotalol from 108 +/- 6 ms to 131 +/- 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 +/- 8 ms to 139 +/- 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 +/- 9 ms to 197 +/- 28 ms, p < 0.05 vs. baseline and vs. sotalol). Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.

Long-term changes in sequence of atrial activation and refractory periods: No evidence for “atrial memory”

The purpose of this study was to test whether the spatial distribution of the atrial refractory period (AERP) and the vulnerability to atrial fibrillation (AF) are altered by long-term changes in the sequence of atrial activation. The spatial distribution of the AERP plays an important role in AF. Changes in the activation sequence have been postulated to modulate atrial repolarization ("atrial memory"). Six goats were chronically instrumented with epicardial atrial electrodes to determine activation time and AERP at 11 different areas of the right (RA) and left (LA) atrium and the Bachmann bundle. Activation time and AERP were measured during sinus rhythm and during prolonged RA and LA pacing (1 week RA pacing, 2 weeks LA pacing, 1 week RA pacing; 150 bpm). Inducibility of AF was determined by the number of atrial sites where single premature stimuli induced AF paroxysms >1 second. During sinus rhythm (106 +/- 4 bpm), AERP was longest at the Bachmann bundle and shortest at the LA free wall (185 +/- 6 ms and 141 +/- 5 ms, P < .001). In five of six goats, an inverse correlation between local activation time and AERP was found during sinus rhythm (r = -0.53 +/- 0.05; P < .05). The increase in atrial rate during RA and LA pacing caused an overall shortening of AERP from 167 +/- 6 ms to 140 +/- 6 ms (P < .001). However, a switch between long-term RA and LA pacing did not significantly change AERP at any of the 11 atrial regions and had no significant effect on AF inducibility. During sinus rhythm, an inverse relationship exists between the sequence of atrial activation and the local refractory period. However, long-term changes in the sequence of atrial activation do not alter the spatial distribution of AERP or the inducibility of AF.

Targeted Modification of Atrial Electrophysiology by Homogeneous Transmural Atrial Gene Transfer

Safe and effective myocardial gene transfer remains elusive. Heterogeneous ventricular gene delivery has been achieved in small mammals but generally with methods not readily transferable to the clinic. Atrium-specific gene transfer has not yet been reported. We hypothesized that homogeneous atrial gene transfer could be achieved by direct application of adenoviral vectors to the epicardial surface, use of poloxamer gel to increase virus contact time, and mild trypsinization to increase virus penetration. We "painted" recombinant adenovirus encoding the reporter gene Escherichia coli beta-galactosidase directly onto porcine atria. Investigational variables included poloxamer use, trypsin concentration, and safety. Using the painting method, we modified the atrial phenotype with an adenovirus expressing HERG-G628S, a long-QT-syndrome mutant. Our results showed that application of virus with poloxamer alone resulted in diffuse epicardial gene transfer with negligible penetration into the myocardium. Dilute trypsin concentrations allowed complete transmural gene transfer. After trypsin exposure, echocardiographic left atrial diameter did not change. Left atrial function decreased on postoperative day 3 but returned to baseline by day 7. Tissue tensile strength was affected only in the 1% trypsin group. HERG-G628S gene transfer prolonged atrial action potential duration and refractory period without affecting ventricular electrophysiology. We show complete transmural atrial gene transfer by this novel painting method. Adaptation of the method could allow application to other tissue targets. Use with functional proteins in the atria could cure or even prevent diseases such as atrial fibrillation or sinus node dysfunction.

Atria Selective Prolongation by NIP-142, an Antiarrhythmic Agent, of Refractory Period and Action Potential Duration in Guinea Pig Myocardium

NIP-142 is a novel benzopyran compound that was shown to prolong the atrial effective refractory period and terminate experimental atrial fibrillation in the dog. In the present study, we examined the effects of NIP-142 on isolated guinea pig myocardium and on the G-protein-coupled inwardly rectifying potassium channel current (acetylcholine-activated potassium current; IKACh) expressed in Xenopus oocytes. NIP-142 (10 and 100 µM) concentration-dependently prolonged the refractory period and action potential duration in the atrium but not in the ventricle. E-4031 and 4-aminopyridine prolonged action potential duration in both left atrium and right ventricle. Prolongation by NIP-142 of the atrial action potential duration was observed at stimulation frequencies between 0.5 and 5 Hz. In contrast, the prolongation by E-4031 was not observed at higher frequencies. Tertiapin, a blocker of IKACh, prolonged action potential duration in the atrium but not in the ventricle. NIP-142 completely reversed the carbachol-induced shortening of atrial action potential duration. NIP-142 (1 to 100 µM), as well as tertiapin (0.1 to 100 nM), concentration-dependently blocked IKACh expressed in Xenopus oocytes; the blockade by NIP-142 was not affected by membrane voltage. In conclusion, NIP-142 was shown to prolong atrial refractory period and action potential duration through blockade of IKACh which may possiblly explain its previously described antiarrhythic activity. NIP-142 has pharmacological properties that are different from classical class III antiarrhythmic agents such as atria specificity and lack of reverse frequency dependence, and thus appears promising for the treatment of supraventricular arrhythmia.

Cibenzoline Attenuates Upregulation of Kv1.5 Channel Gene Expression by Experimental Paroxysmal Atrial Fibrillation

Antiarrhythmic drugs exert their effects by inhibiting the ion channels of cardiomyocytes. However, these effects could also modify the ionic environment around them, and thereby affect the expression of ion channels, leading to biochemical enhancement or attenuation of the antiarrhythmic effects. To test this hypothesis, the physiological and biochemical effects of cibenzoline were evaluated in a rapid atrial pacing model in rats. In rats with rapid atrial pacing, pretreatment with cibenzoline significantly inhibited the increases in Kv1.5 mRNA at 2 hours and immunoreactive protein at 4 hours by 35 +/- 15% and 30 +/- 10%, respectively. These effects were observed only in the rapid atrial pacing group, not in the sham-operated group. With cibenzoline pretreatment, 4-hour rapid atrial pacing resulted in significant prolongation of the atrial refractory period compared to the untreated group even after removal of cibenzoline. In contrast, the sham and rapid atrial pacing model with and without cibenzoline pretreatment showed similar acute physiological responses to cibenzoline. In conclusion, in addition to the acute physiological effects, pretreatment with cibenzoline exerted pleiotropic effects of inhibition of Kv1.5 channel upregulation by rapid pacing, implying differences in the cibenzoline effects when administered before and after onset of paroxysmal atrial fibrillation.

Synergistic Action of Atrial Dilation and Sodium Channel Blockade on Conduction in Rabbit Atria

The aim of this study was to investigate the interaction of atrial dilation and blockade of the rapid sodium channel on atrial conduction and degree of anisotropy. The right atrium was acutely dilated by increasing intra-atrial pressure from 2 to 9 cm H2O in 14 isolated rabbit hearts. A rectangular mapping array of 240 electrodes (spatial resolution 0.5 mm) was positioned on the free wall of the right atrium during pacing from four different directions at intervals of 240 and 140 msec. In nondilated atria, 0.5 and 1.0 mg/L of the use-dependent INa blocker flecainide prolonged the total conduction time under the mapping electrode by 15% to 75%. In dilated atria, flecainide depressed conduction by 24% to 89% (P < 0.05). The incidence of intra-atrial conduction block increased from 0.6%-0.8% to 3.3%-7.2% in nondilated atria and from 3.9%-4.6% to 13%-21% in dilated atria (P < 0.05). The direction of activation relative to the crista terminalis and major pectinate muscles was of major importance for occurrence of conduction block. During rapid pacing, the degree of anisotropy in conduction increased by the combination of atrial dilation and flecainide (1.0 mg/L) from 1.7 +/- 0.1 to 2.2 +/- 0.4 (P < 0.05). The effects of dilation and flecainide on conduction were clearly synergistic. The effect of flecainide on the atrial refractory period also was enhanced by atrial dilation. In dilated atria, blockade of the rapid sodium channels caused a higher degree of local conduction delay and intra-atrial conduction block than in nondilated atria.

Effects of stimulation with pulsatile continuous electrical current on atrial electrophysiological properties. Experimental study of atrial fibrillation in dogs

OBJECTIVE: To assess whether atrial stimulation with pulsatile continuous electrical current induces atrial fibrillation and to evaluate its effects on atrial electrophysiological properties as well as the atrial histological alterations. METHODS: Twenty-two dogs underwent right lateral thoracotomy and implantation of pacemaker electrodes in the sulcus terminalis (ST), in the right atrial appendix (RAb), and in the posteroinferior region of the left atrium (LA). A pair of electrodes was sutured to the right atrial appendix for stimulation with a 9-volt alkaline battery connected to a system (LM 555) that transforms the linear continuous energy of the battery into a pulsatile continuous current for 60 minutes. Atrial epicardial biopsy was performed before and after atrial stimulation. RESULTS: No differences were observed in the durations of the effective atrial refractory periods. The times of intra-atrial and interatrial conduction, as well as that of atrial extrastimuli, were prolonged. The duration of atrial electrograms was prolonged during sinus rhythm and programmed atrial stimulation; in 68% of the dogs, atrial fibrillation was induced and was sustained. Interstitial edema and bands of cellular contraction were observed in the subepicardium on optical microscopy, as were intense myofibrillar disorganization and an increase in the size of the mitochondria on electron microscopy. CONCLUSION: That technique of atrial stimulation induces atrial fibrillation and causes atrial changes that increase atrial vulnerability to the appearance of atrial fibrillation.