Skip Navigation

Cardiovascular Research 2003 60(2):307-314; doi:10.1016/S0008-6363(03)00536-4
© 2003 by European Society of Cardiology
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chandra, P.
Right arrow Articles by Rosen, M. R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chandra, P.
Right arrow Articles by Rosen, M. R
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2003, European Society of Cardiology

Left atrial pacing induces memory and is associated with atrial tachyarrhythmias

Parag Chandra, Tove S Rosen, Bengt Herweg1, Peter Danilo, Jr. and Michael R Rosen*

Departments of Pharmacology and Pediatrics and Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH7West-321, New York, NY, USA

*Corresponding author. Present address: Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, PH7West-321, New York, NY, USA. Tel.: +1-212-305-8754; fax: +1-212-305-8351. Email address: mrr1{at}columbia.edu

Received 12 September 2002; accepted 22 July 2003


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Objective: Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. Methods: A total of 12 chronically instrumented mongrel dogs in complete heart block were paced AV sequentially from the left or right atrium for 7–28 days, and then recovered in normal sinus rhythm for 21 days. Rate histograms were recorded during the entire period, and electrophysiological studies were conducted to note changes in the atrial gradient, effective refractory period and atrial rhythm. No atrial arrhythmias were seen in eight control animals that were instrumented but not paced. Results: Left atrial pacing was associated with a decreased atrial gradient and occurrence of atrial tachycardias that appeared during pacing and persisted during recovery from pacing. In contrast, right atrial pacing did not alter the atrial gradient significantly. Atrial tachycardias occurring during right atrial pacing disappeared after cessation of pacing, when dogs recovered in sinus rhythm. The effective refractory period did not change in either group. Conclusions: Pacing-induced impulse initiation from the left atrium alters the atrial gradient and is associated with atrial tachycardias. These changes in atrial gradient occur in the absence of ERP changes and may be early predictors of an arrhythmogenic substrate.

KEYWORDS Arrhythmia (mechanism); ECG; Remodeling; Repolarization; Supraventricular arrhythmia


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Electrical remodeling of the atria occurs in human subjects and in animal models [1–6]. In animals, it is often induced by atrial pacing at 400–900 beats per minute (bpm). The resultant shortening of atrial effective refractory periods (ERP) is considered a marker of electrical remodeling [1–3]. Such rapid atrial pacing also alters atrial myocardial activation.

We previously demonstrated that 20–120 min of pacing from the left atrial appendage (LAA), at rates slightly higher than sinus alters activation and modifies repolarization [7]. The modification of repolarization occurs in a manner consistent with cardiac memory [8,9], defined electrocardiographically in ventricle as a change in the T wave vector during sinus rhythm to assume an axis tracking the QRS vector of previously occurring ventricular arrhythmic or paced beats. Increasing the rate of atrial stimulation enhances accumulation of atrial memory in a manner analogous to memory accumulation in ventricle [7]. Based on these observations we hypothesized that subtle changes in atrial rate originating from a focus outside the sinus node might provide a substrate for atrial memory and that this might contribute to altered cardiac rhythm. We tested this hypothesis by pacing the atria for 1–4 weeks from extra-sinus sites, and determining the effects of altered activation at physiological rates on the expression of atrial memory, the atrial ERP and cardiac rate and rhythm.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Animal preparation
The study conformed to the rules of the Columbia University Animal Care and Use Committee. A total of 12 female mongrel dogs weighing 24–26 kg were anesthetized with thiopental sodium (17 mg/kg, i.v.) and ventilated with isoflurane (1.5–2%) and oxygen (2 l/min). Morphine sulphate (0.15 mg/kg) was injected epidurally for postoperative analgesia. Using sterile techniques, a right intercostal thoracotomy was performed, and bipolar electrodes (Medtronic model 5058) were attached epicardially to the LAA or the right atrial appendage (RAA) and the right ventricular (RV) free wall. Leads were tunneled subcutaneously and connected to a Medtronic 7864B dual chamber pulse generator implanted in the right posterior thorax. Bipolar electrodes for pacing and recording were attached to the RAA, LAA and mid right atrium (MRA), subcutaneously tunneled to the right posterior thorax and exteriorized. Complete heart block was produced by injecting 0.1–0.3 ml of 37% formaldehyde into the basal ventricular septum in the region of the atrio-ventricular (AV) node [7]. This permitted AV sequential pacing to be performed with sufficient AV delay (see below) to facilitate complete visualization of the atrial T (Ta) wave. PTa waves were identified as starting at the onset of the P wave and terminating at the end of the Ta wave.

After surgery the dogs recovered for {approx}3 weeks, during which they were laboratory trained to allow experimentation in the conscious state and monitored to demonstrate electrical stability. All dogs were in sinus rhythm throughout this period. A total of 12 dogs received P-synchronous pacing delivered to the ventricles with a sensed AV delay of 120 ms for dogs with RAA leads and 80 ms for dogs with LAA leads. These delays permitted the normal sequence of atrioventricular contraction to be maintained as has been suggested in the literature [10,11] and was tested and verified in three animals (data not shown). Another eight control animals were prepared and instrumented as above and their pacemakers were set in a ventricular demand mode at a rate of 60 bpm.

2.2. Experimental protocol
Experiments were performed on conscious animals resting on their left sides. The protocol was designed to study the effects of differences in site of atrial impulse initiation on the atrial gradient [7] and ERP. Four dogs were paced at 120 bpm from the LAA and five from the RAA for 21–28 days using AV sequential pacing. Effective AV delays were maintained equivalent in both groups. All dogs then recovered in sinus rhythm during P synchronous ventricular pacing for 21 days. We have shown previously that ventricular pacing at this rate for similar durations does not alter hemodynamics, coronary flow, contractility or cell capacitance [9,12].

The pacemaker acquisition programs permitted rate histograms to be derived from cycle length measurements of all intervals occurring during the entire period of pacing and recovery in eight dogs. In six of these dogs the control period before pacing was 3–14 days. During this control period sinus rhythm persisted and no atrial arrhythmias were observed. In those dogs in which rate histograms were not recorded, the control period was 3 h. Atrial arrhythmias were defined as premature beats or paroxysmal tachycardias whose rates were over 150 bpm, which was faster than the dominant sinus rhythm, and of a different population of rhythms, per the histogram analysis. Rates and rhythms were recorded both via the pacemaker units and via the standard ECG recording system in the laboratory.

Prior to starting atrial pacing and at times indicated by arrows in Fig. 1, an electrophysiologic study was performed. This was done using 2:1 AV sequential pacing (Bloom DTU 210) at an atrial Basic Cycle Length (BCL) of 400 ms, with stimuli delivered via the mid-right atrial electrode in all dogs. During this protocol, paced AV delay of 220±20 ms allowed for inter-animal variability. The ventricle was stimulated after every second atrial beat (2:1) allowing complete visualization and analysis of alternate Ta waves and maintenance of a physiological ventricular rate.


Figure 1
View larger version (27K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Experimental protocol. ECG recordings and ERP measurements were made on the days marked with arrows in four LAA and four RAA paced dogs. Rate histograms were recorded throughout the protocol. During control and recovery animals were in sinus rhythm. C, control; RAP and LAP, right and left atrial pacing, respectively.

 
During each electrophysiologic study we recorded the ECG and ERP at the right and left atrium while pacing from the RA bipolar electrode and then from the LA bipolar electrode in all dogs. The ERP was measured by introducing single extra-stimuli after ten beat drive trains at BCL of 400, 300 and 200 ms. Basic (S1) and premature (S2) stimuli were 2-ms square waves at twice threshold current, with S1–S2 decrements of 2 ms. The ERP was the shortest S1–S2 interval that induced a propagated response, manifested as a P wave on ECG.

2.3. ECG recording and analysis
A Mida 1000 (Ortivus) acquisition system was used to record the unfiltered, signal-averaged ECG using XYZ Frank leads. Data were analyzed with MIDA 1200 and 1000 Ortivus software. To assess changes in P and Ta waves, PTa isoareas were measured in XYZ leads. The spatial atrial gradient was calculated using a formula originally developed by Wilson et al. [13] whose rationale and adaptation to quantify memory in atrium was previously reported [7]:


Formula

Cardiac rate and rhythm and P wave morphology were studied using standard bipolar lead I and an augmented unipolar lead, recorded and analyzed using Ponemah acquisition software (Gould Instruments). Electrograms recorded simultaneously from the LA and RA, were used as a gross estimate of the atrial activation sequence.

2.4. Statistical analysis
Data were analyzed using SPSS 10.0 software and expressed as mean±S.E.M. Repeated measures ANOVA was used to compare multiple sequential measurements. Post hoc multiple comparisons were performed by Bonferroni's method where equal variances were assumed. Fisher's exact test was used to compare incidences. P<0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Atrial tachycardias and P wave morphology
Mean sinus rate for all 12 RA- or LA-paced dogs at control was 96±3 bpm. Atrial tachycardias appeared as regular atrial rhythms with rates >150 bpm within 1 day after the onset of pacing in both groups of dogs. This was in contrast to the eight instrumented control animals, which had no atrial arrhythmias during their 3 weeks of observation. Control sinus rates in these animals were 124±4 bpm, significantly faster than the AV-paced animals and likely reflecting the low ventricular rates at which the control animals’ pacemakers were programmed. In the LA paced (LAP) animals the sinus rate was 96±4 bpm at control and the tachycardia rate was 193±17 bpm (P<0.05 vs. control) at 7 days of pacing. Tachycardias recurred through the entire duration of pacing and tachycardias of spontaneous onset were noted repeatedly during recovery in all previously LA paced dogs (summary in Fig. 2, representative experiments in Fig. 3). Atrial tachycardias competing with the paced and sinus rhythm were also noted in all LA paced dogs during electrophysiological study at BCL of 400 ms (see below).


Figure 2
View larger version (29K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Rate of sinus rhythm before pacing and rates of atrial tachycardias in left (LAP) and right (RAP) atrially paced dogs. Results for days 7 and 28 of pacing (P) and days 7 and 21 of recovery (R) are shown. n = 5 for RAP dogs and n = 7 for LAP dogs, except on day 28 of pacing, where n = 4 for LAP dogs. Note that during sinus rhythm and pacing, there are no differences between LAP and RAP. However, during recovery, tachycardias are seen in LAP only (cross-hatched bars).

 

Figure 3
View larger version (23K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Atrial rate histograms from one RAP dog (A) and one LAP dog (B). At control both have a normal atrial rate distribution. The black bar represents the pacing rate of 120 bpm. On pacing day 1 there is almost complete capture in both dogs. At 7 and 28 days of pacing, the LAP histogram shows tachycardias (>150 bpm). The RAP dog, in comparison persists in almost complete capture at 120 bpm. During recovery, the RAP dog immediately returns to a rate distribution similar to control and this persists through the 21 days of recovery. In contrast the LAP dog has tachycardias that are prominent during pacing and through day 21 of recovery. Axis represents % of beats (vertical) at various heart rates (horizontal).

 
Atrial tachycardias also appeared after initiation of pacing in the RA paced (RAP) animals. The control sinus rate was 96±5 bpm and the tachycardia rate was 190±26 bpm (P<0.05 vs. control) at pacing day 7. However, in contrast to the LAP dogs, the tachycardias in RAP dogs terminated when pacing was discontinued and the dogs were recovering in sinus rhythm (Figs. 2 and 3Go).

Fig. 3 illustrates the differences in response to RA and LA pacing via atrial rate histograms from one dog paced from the RA and one from the LA, at control, days 1 and 28 of pacing, and days 1, 7 and 21 of recovery. In both dogs at control, there is a roughly bell-shaped distribution of atrial rates where the greater number of beats is <120 bpm. All histograms from LAP dogs showed tachycardias after onset of pacing, which continued throughout recovery. In contrast, all histograms from RAP dogs revealed almost complete capture at 120 bpm during pacing with only brief bursts of tachycardia and a near normal rate distribution during recovery (Fig. 3). Atrial rates less than paced rates were not due to under-sensing because the device used does not sense intervals greater than pacing CL at the lower rate limit. Rather, those long atrial intervals were collected when the lower rate limit of the device was reduced during test pacing periods. These results suggest that LA pacing for 21–28 days results in an arrhythmia pattern that persists for an interval greater than or equal to the period of pacing. This is in contrast to RA pacing where all arrhythmic activity ceases on cessation of pacing.

To test whether 3–4 weeks of pacing was essential to induce persistent arrhythmic activity, we studied three additional dogs, paced from LA for 7, 10 and 14 days. All had arrhythmic activity that persisted throughout their recovery periods (which were 14, 21 and 21 days, respectively). Hence, the duration of LA pacing required for arrhythmias to persist well into recovery is shorter than the 21–28 days used in most dogs.

We also studied the incidence of competing atrial impulses that occurred during brief periods of pacing at 400 bpm for determination of the ERP. There was almost the same incidence of induced tachycardias during the 21–28-day periods of RA and LA pacing (21 events in 24 determinations during LAP and 11 events during 20 determinations during RAP, P>0.05). However, during the recovery protocol the LAP group had a higher incidence of induced arrhythmias (19 of 35 determinations) than the RAP group (two of 25 determinations) (P<0.05).

Fig. 4A shows representative ECG and electrograms from one dog. During sinus rhythm before initiation of pacing, leads I and aVR reveal sinus P wave morphology, and simultaneously recorded electrograms confirm normal atrial activation (MRA->RAA->LAA). Fig. 4B depicts a competing atrial tachycardia during RAP at CL of 400 ms. The competing tachycardia complexes are similar in morphology and activation sequence to sinus P waves. Such competing tachycardias were observed in all dogs during pacing for 21–28 days, and in the LAP>RAP dogs during the 21 days of recovery as well. These rhythms were overdrive suppressible and reset was seen with continued right atrial pacing.


Figure 4
View larger version (28K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 ECG and electrogram recordings from an LAP dog during sinus rhythm and RA pacing at CL of 400 ms. (A) Normal sinus complexes are seen; (B) competing atrial tachycardia is seen during RA pacing. Paced complexes followed by reset of the tachycardia are marked by double arrows. Competing tachycardia complexes are seen as P waves with a morphology similar to the sinus P waves. The MRA electrogram for each of these competing complexes occurs before the LAA electrogram, confirming the RA origin of the tachycardia complexes.

 
3.2. Changes in atrial gradient
Fig. 5 shows the change in atrial gradient in LA and RA paced dogs during pacing and recovery, normalized to their respective controls. The atrial gradient in LAP dogs decreased from 6.3±0.18 µVs at control to 2.4±0.27 µVs at 21 days of recovery (P<0.05). In RAP dogs, atrial gradient was 3.9±0.51 µVs at control and 6.08±1.54 µVs at 21 days of recovery (P>0.05).


Figure 5
View larger version (21K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 5 Changes in atrial gradient (normalized to control) are shown during pacing and recovery. The atrial gradient decreases in the LAP dogs while there is no change in the RAP. The two curves differ (P<0.05).

 
Fig. 6A shows the three-dimensional orientation of the P wave vector during right and left atrial pacing, and Fig. 6B, the atrial gradient vector constructed from XYZ PTa isoareas on days 1 of pacing and 1 and 21 of recovery. The atrial gradient vector is directed oppositely during right and left pacing (P1). During recovery, R1 and R21, the atrial gradient vectors for the LAP and RAP groups, are in opposite directions and follow their respective P wave vectors, demonstrating that memory has been induced.


Figure 6
View larger version (38K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 6 (A) P wave vectors during RA and LA pacing plotted in three dimensions using XYZ coordinates of the P wave (mV). Note the different direction of the P waves when paced from RAA or LAA. Broken traces are reference lines. (B) Evolution of atrial gradient vector during RA and LA pacing and recovery. The corresponding P and Ta waves are shown next to the vectors. The atrial gradient vector is plotted using the XYZ PTa voltage–time integrals as coordinates (µVs). Three vectors each are constructed for RA and LA pacing: P1, pacing day 1; R1 and R21, recovery days 1 and 21. All vectors originate from an arbitrary point with coordinates equal to 0. Thin vertical traces are reference lines.

 
We also studied the evolution and resolution of the atrial gradient in the three animals paced for 7–14 days. In the animal paced for 14 days the atrial gradient manifested a change and time course similar to those of the animals paced for the full duration of the protocol. In the animals paced for 7 and 10 days the change in atrial gradient was smaller, and the gradient approximated control within 14 days of cessation of pacing.

3.3. Effective refractory period
ERP was measured at MRA, RAA and LAA at CL of 400, 300 and 200 ms throughout the protocol. There was no significant change in ERP during the entire pacing and recovery period in either group (Fig. 7, P>0.05). ERP testing also induced brief (1–10 s), self-terminating bursts of atrial fibrillation in three of five RA-paced dogs, two of three dogs paced from LA for 7–14 days, and three of four dogs paced from LA for 21–28 days.


Figure 7
View larger version (24K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 7 ERP from MRA, RAA and LAA at BCL of 300 ms in RA paced (A) and LA paced (B) dogs. There is no change in ERP at any site during pacing or recovery. Similar results were obtained at CL of 400 and 200 ms (data not shown).

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
We previously demonstrated that LA pacing for 2 h induces atrial memory, seen as a change in the atrial gradient [7]. Moreover, the faster the rate of pacing the greater the extent of change. Arrhythmias did not occur during the brief (2 h) pacing periods in that study. We assumed, based on earlier work in canine ventricle [9], that pacing for 3–4 weeks would induce further accumulation of memory, and, in initiating the current study, a major goal was to determine the kinetics of evolution and resolution of the memory process in atrium. What was unanticipated and provides the novel aspect of the present study, was that competing atrial tachycardias occurred during RA and LA pacing, but only those arising during LA pacing continued to recur after returning to sinus rhythm.

The origin and mechanism for these tachycardias was not determined in the present study. Given the general morphology of the tachycardia beats, the origin would appear to be right atrial, with a site in or near the sinus node. Given the large area occupied by the canine sinus node [14] it is difficult to speculate on which possibility is more likely. More obvious is that the tachycardia was not simply a normal sinus rhythm. Rather, tachycardia rates (Figs. 2 and 3Go) were far more rapid than would be expected for a normal sinus rhythm.

As would have been predicted from our earlier study [7], the total of 7–8 weeks’ LA pacing and recovery from pacing significantly decreased atrial gradient (Fig. 4). There was a concomitant and insignificant upward shift in the atrial gradient as a result of RA pacing and recovery over the same period. This result is not surprising, as during LA pacing the atria were activated via a pathway opposite to that of sinus rhythm. In contrast, with RA pacing the pathway was likely far closer to that which characterizes sinus rhythm. Studies in ventricle have demonstrated that a key determinant of memory is an altered activation sequence, which sets in motion alterations in stress/strain on the myocardium and, via an angiotensin II-modulated pathway, initiates changes in the transmural gradient for repolarization [15]. Moreover, whether the altered repolarization reflects electrophysiologic remodeling alone or incorporates elements of structural and/or autonomic remodeling remains to be tested.

Memory is a specialized form of remodeling. Most studies of electrophysiologic remodeling in atrium employ atrial pacing at 400–900 bpm, and measure atrial ERP as an indicator of remodeling [1–5]. Hence, in the current study we measured atrial ERP to determine whether a change in activation in the setting of only a modest, yet chronic rate increase would suffice to alter atrial ERP. That ERP did not change during pacing or as a result of the atrial tachycardias that occurred during pacing and recovery suggests that the change in atrial gradient may be a more sensitive measure than ERP of alterations that ectopic sites of impulse initiation firing at modest tachycardia rates induce in the atrial electrophysiologic substrate. This observation is in no way at odds with other studies that have shown shortening of atrial ERP at very rapid atrial pacing rates [1–5].

The atrial tachycardias that occurred were either expressed during the pacing period (RAP and LAP dogs) or persisted after pacing had ceased (LAP dogs, only). The incidence of tachycardias induced by premature stimulation of right and left atria was equal during the pacing period. However, incidence of competing atrial tachycardias during recovery from pacing was significantly greater in the animals that had been chronically paced from the LA, regardless of whether the premature stimulation was from left or right atrium. This result is complementary to the incidence of spontaneously occurring tachycardias monitored during the pacing and the recovery periods.

The memory and the type of arrhythmic behavior found in our studies focus attention on site and pattern of stimulation as critical in the induction of an arrhythmic substrate. Interestingly, the behavior patterns manifested are reminiscent of those previously characterized in studies of cortical neurons. In networks of such neurons, for a given site of tetanic stimulation, both potentiation and depression of firing are pathway-specific rather than neuron-specific [16]. Moreover, the modified pathways always reside within the previously described capability of the network [17,18]. This property of networks has been offered as one explanation of the evolution of memory patterns in brain.

If one considers the intact atrium to be a network of cells, then the parallels between this system and the neural networks are obvious [19]. Activation initiated from the left atrium initiates propagation via a pathway already present although not routinely used in the fashion entrained by the LA stimulus. Once this pathway is activated, two changes occur: one is the alteration in atrial gradient, the other a sequence of beats of variable duration and within a range of rates compatible with preexisting electrophysiologic properties of the atrium. However, whether the change in atrial gradient is essential to the occurrence of the tachycardia or is simply an accompaniment is uncertain.

The phenomena characteristic of neural networks and demonstrated here in atrium may be highly significant in the expression of atrial arrhythmias and fibrillation. The most obvious association would involve situations where pulmonary venous foci initiate atrial fibrillation [20,21]. Here, isolated foci in an LA location fire repeatedly or intermittently over time, and yet entrain the rest of the atrial tissue such that ultimately, fibrillation ensues. Whether the types of atrial tachycardias seen in our study ultimately would facilitate atrial fibrillation has not been tested. However, the parallels are obvious: in both instances there is the occurrence of an ongoing ectopic focus that provides abnormal activation, a change in repolarization and the facilitation of a pattern of firing that is abnormal. One obvious dissimilarity, however, is that the pulmonary venous foci tend to fire in irregular salvos having high frequencies [20]. Whether it is the total number of beats arising from an ectopic site (in which case the high frequency, intermittent pulmonary venous foci and the lower frequency, persistent left atrial paced foci would be part of the same mechanistic continuum) or the frequency characteristics of the abnormal impulses (in which case the two types of foci would represent different mechanistic universes) remains to be tested. In either event, however, our observations suggest that stimuli promoting the occurrence of memory in the atria would tend to be arrhythmogenic and that techniques for evaluating the occurrence of atrial memory might provide early markers of arrhythmias to come.


   Acknowledgements
 
The authors express their gratitude to Ana Almonte for her assistance with some of the experiments and to Eileen Franey for her careful attention to the preparation of the manuscript. This work was supported by the National Heart, Lung and Blood Institute Grant HL-67449 and by The Center for Molecular Therapeutics.


   Notes
 
1 Present address: Electrophysiology and Arrhythmia Services, Division of Cardiovascular Disease, Harbourside Medical Tower, Suite 630, Four Columbia Drive, Tampa, FL 33606, USA. Back

Time for primary review 25 days


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Morillo C.A., Klein G.J., Jones D.L., Guiraudon C.M. Chronic rapid atrial pacing: structural, functional and electrophysiological characteristics of a new model of sustained atrial fibrillation. Circulation (1995) 91:1588–1595.[Abstract/Free Full Text]
  2. Wijffels M.C.E.F., Kirchhof C.J.H.J., Dorland R., Allessie M.A. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation (1995) 92:1954–1968.[Abstract/Free Full Text]
  3. Allessie M., Konings K Wijffels M. Atrial arrhythmias: state of the art. DiMarco J.P., Prystowsky E.N., eds. (1995) Armonk, NY: Futura Publishing. 155–161.
  4. Gaspo R., Bosch R.F., Talajic M., Nattel S. Functional mechanisms underlying tachycardia-induced sustained atrial fibrillation in a chronic dog model. Circulation (1997) 96:4027–4035.[Abstract/Free Full Text]
  5. Yue L., Feng J., Gaspo R., Li G.R., Wang Z., Nattel S. Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res (1997) 81:512–525.[Abstract/Free Full Text]
  6. Van Wagoner D.R., Pond A.L., Lamorgese M., Rossie S.S., McCarthy P.M., Nerbonne J.M. Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res (1999) 85:428–436.[Abstract/Free Full Text]
  7. Herweg B., Chang F., Chandra P., Danilo P. Jr., Rosen M.R. Cardiac memory in canine atrium: identification and implications. Circulation (2001) 103:455–461.[Abstract/Free Full Text]
  8. del Balzo U., Rosen M.R. T wave changes persisting after ventricular pacing in canine heart are altered by 4-aminopyridine but not by lidocaine. Circulation (1992) 85:1464–1472.[Abstract/Free Full Text]
  9. Shvilkin A., Danilo P. Jr., Wang J., Burkhoff D., Anyukhovsky E.P., Sosunov E.A., et al. Evolution and resolution of long-term cardiac memory. Circulation (1998) 97:1810–1817.[Abstract/Free Full Text]
  10. Janosik D.L., Pearson A.C., Buckingham T.A., Labovitz A.J., Redd R.M. The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing. J Am Coll Cardiol (1989) 14:499–507.[Abstract]
  11. Dabrowska-Kugacka A., Lewicka-Nowak E., Kutarski A., Zagozdzon P., Swiatecka G. Hemodynamic effects of alternative atrial pacing sites in patients with paroxysmal atrial fibrillation. Pacing Clin Electrophysiol (2003) 26:278–283.[CrossRef][Medline]
  12. Yu H., McKinnon D., Dixon J.E., Gao J., Wymore R., Cohen I.S., et al. Transient outward current, Ito1, is altered in cardiac memory. Circulation (1999) 99:1898–1905.[Abstract/Free Full Text]
  13. Wilson F.N., Macleod A.G., Barker P.S., et al. The determination and significance of the areas of the ventricular deflections of the electrocardiogram. Am Heart J (1934) 10:46–61.[CrossRef][ISI]
  14. Boineau J.P., Schuessler R.B., Hackel D.B., Miller C.B., Brockus C.W., Wylds A.C. Widespread distribution and rate differentiation of the atrial pacemaker complex. Am J Physiol (1980) 239:H406–415.[ISI][Medline]
  15. Ricard P., Danilo P. Jr., Cohen I.S., Burkhoff D., Rosen M.R. A role for the rennin-angiotensin system in the evolution of cardiac memory. J Cardiovasc Electrophysiol (1999) 10:545–551.[ISI][Medline]
  16. Jimbo Y., Tateno T., Robinson H.P. Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons. Biophys J (1999) 76:670–678.[Abstract/Free Full Text]
  17. Shahaf G., Marom S. Learning in networks of cortical neurons. J Neurosci (2001) 21:8782–8788.[Abstract/Free Full Text]
  18. Marom S., Shahaf G. Development, learning and memory in large random networks of cortical neurons: lessons beyond anatomy. Q Rev Biophys (2002) 35:63–87.[CrossRef][ISI][Medline]
  19. Rosen MR, Binah O, Marom S. Cardiac memory and cortical memory: do learning patterns in neural networks impact on cardiac arrhythmias? Circulation (in press).
  20. Haissaguerre M., Jais P., Shah D.C., Takahashi A., Hocini M., Quiniou G., et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med (1998) 339:659–666.[Abstract/Free Full Text]
  21. Jais P., Haissaguerre M., Shah D., Chouairi S., Gencel L., Hocini M., et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation (1997) 95:572–576.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chandra, P.
Right arrow Articles by Rosen, M. R
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chandra, P.
Right arrow Articles by Rosen, M. R
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?