Published online before print May 24, 2001, doi: 10.1161/hh1101.092187
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© 2001 American Heart Association, Inc.
Integrative Physiology |
Mechanisms Underlying the Reentrant Circuit of Atrioventricular Nodal Reentrant Tachycardia in Isolated Canine Atrioventricular Nodal Preparation Using Optical Mapping
From the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Ind.
Correspondence to Douglas P. Zipes, MD, Krannert Institute of Cardiology, Indiana University School of Medicine, 1111 W 10th St, Indianapolis, IN 46202. E-mail dzipes{at}iupui.edu
Abstract
Abstract—The reentrant pathways underlying different types of atrioventricular (AV) nodal reentrant tachycardia have not yet been elucidated. This study was performed to optically map Koch’s triangle and surrounding atrial tissue in an isolated canine AV nodal preparation. Multiple preferential AV nodal input pathways were observed in all preparations (n=22) with continuous (73%, n=16) and discontinuous (27%, n=6) AV nodal function curves (AVNFCs). AV nodal echo beats (EBs) were induced in 54% (12/22) of preparations. The reentrant circuit of the slow/fast EB (36%, n=8) started as a block in fast pathway (FP) and a delay in slow pathway (SP) conduction to the compact AV node, then exited from the AV node to the FP, and rapidly returned to the SP through the atrial tissue located at the base of Koch’s triangle. The reentrant circuit of the fast/slow EB (9%, n=2) was in an opposite direction. In the slow/slow EB (9%, n=2), anterograde conduction was over the intermediate pathway (IP) and retrograde conduction was over the SP. Unidirectional conduction block occurred at the junction between the AV node and its input pathways. Conduction over the IP smoothed the transition from the FP to the SP, resulting in a continuous AVNFC. A "jump" in AH interval resulted from shifting of anterograde conduction from the FP to the SP (n=4) or abrupt conduction delay within the AV node through the FP (n=2). These findings indicate that (1) multiple AV nodal anterograde pathways exist in all normal hearts; (2) atrial tissue is involved in reentrant circuits; (3) unidirectional block occurs at the interface between the AV node and its input pathways; and (4) the IP can mask the existence of FP and SP, producing continuous AVNFCs.
Key Words: atrioventricular node • atrioventricular nodal reentrant tachycardia • optical mapping
Extensive evidence supports the concept that dual atrioventricular (AV) nodal conduction pathways are the basis for AV nodal reentrant echo beats (EBs) and sustained AV nodal reentrant tachycardia (AVNRT).1 2 3 However, the complete reentrant circuit has yet to be demonstrated. Data from mapping and ablation studies in AVNRT suggested that the fast and slow pathways represented different atrio-nodal connections rather than the result of functional longitudinal dissociation.4 5 In addition, at least 3 types of AVNRT have been characterized,5 and multiple AV nodal inputs may exist as well.4 The anatomic locations of the reentrant pathways related to variant types of AVNRT have not been completely determined. Furthermore, although an abrupt "jump" in AH interval is believed to represent dual AV nodal physiology, it is not clear why some patients with AVNRT have no jump and other patients without AVNRT do have a jump.6
Accordingly, this study was performed to (1) characterize the reentrant circuit in 3 types of AVNRT, (2) establish the location of atrio-nodal pathways and site of initiating unidirectional block, and (3) determine mechanisms of continuous and discontinuous AV nodal function curves (AVNFCs).
Materials and Methods
AV Nodal Preparation
The AV nodal preparations used in the present
study were modified from canine atrial preparation described
previously.7 Adult mongrel
dogs were anesthetized. Hearts were rapidly excised and
perfused through the aorta with cardioplegic solution. After the
ventricle, left atrium, right atrial appendage, and sinoatrial node
tissues were trimmed away, the proximal and distal right
coronary artery and distal left circumflex artery were
separately cannulated. The preparation was perfused with Tyrode’s
solution at 37°C through the coronary cannulae at a flow rate
of 20 mL/min.
Fluorescent Optical Mapping System
and Data Processing
The optical mapping system was constructed as
described
previously.8 9 The
locations of the mapped area (19.5x19.5 mm) were verified using a
CCD video camera as shown in
Figure 1A
. A bipolar electrode was used to record His
bundle electrograms. Pacing was performed from the anterior limbus of
the fossa ovalis near the fast pathway (FP)
(Figure 1A). The fluorescent action potential
(AP) signals were filtered at 1000 Hz. The time of activation
was determined from the maximum amplitude of the APs (APA-max). The
benefits and limitations of this method are discussed in an online data
supplement available at http://www.circresaha.org. The conduction
velocity in the different regions was determined by measuring 3 to 5
mapping sites along the direction of the propagating wavefront.
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Experimental Protocol
After 30 minutes of recovery from the cardioplegic
solution, the preparation was stained with 0.2 mg of di-4-ANEPPS at a
concentration of 
2 µmol/L and then was continuously perfused with
a solution containing cytochalasin D at a concentration of 30
µmol/L.9 Optical data were
obtained either during atrial programmed stimulation or during
spontaneous junctional rhythm. After optical mapping, intracellular
microelectrode recordings were obtained using techniques
described
previously.8
Statistical Analysis
Data are expressed as mean±SEM. ANOVA was performed
for the AP parameters in the
Table. Other statistical analyses were performed using Student’s t test. The
criterion for statistical significance was P<0.05.
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Results
Characterization of AV Nodal Conduction
Properties
A picture of an AV nodal preparation is shown in
Figure 1A
. The FP was identified as the earliest retrograde
atrial activation sites located near the anterior atrial septum outside
Koch’s triangle (KT). The slow pathway (SP) region between the
coronary sinus (CS) ostium and the tricuspid annulus was
divided equally into 3 zones
(Figure 1B). Optical APs recorded during atrial pacing at
800 ms are shown in
Figure 1C. Representative optical and
intracellular APs obtained from the atrium, FP, transitional zone, AV
node, and SP are superimposed and displayed in
Figure 1D. Each optical AP represents a voltage
signal summated from many cells. The optical AP duration (APD)
was expected to be longer than the intracellular APD as shown in
Figure 1D, especially in the AV nodal and SP areas. Thus,
repolarization times cannot be determined accurately from these optical
APs and were measured from microelectrode recordings. In
general, the configuration of the optical APs appeared to be similar to
the intracellular APs except in areas with slow conduction, such as the
AV node or SP.
Intracellular APs recorded in different anatomic
regions (see
Table)
were characterized into 3 groups as atrial, transitional, and AV nodal
cells, consistent with the results of previous
studies.10 11 APs
obtained from the atrium, FP, and SP zone 1 did not have significant
differences (P>0.05 in all
groups), suggesting that similar types of atrial tissue surrounded KT.
There were no significant differences
(P>0.05 in all groups for all
AP parameters) between transitional cells and SP zone 2.
APs recorded in zone 3, particularly in deeper layers or near the
edge of the tricuspid valve, had identical configurations
(P>0.5 in all groups) compared
with those recorded in the AV node, suggesting a posterior
extension of the AV node and therefore an asymmetrical transitional
zone surrounding the AV node. The SP was located in zones 2 and 3 and
consisted of 2 types of cells, one being the transitional cell and the
other being the AV nodal cell. From the FP to the transitional zone and
AV node, AP amplitude, maximum diastolic potential, and
maximum rate of rise at phase 0 (dV/dt) gradually decreased and
resulted in a progressive delay in AV nodal conduction. The longest APD
at 90% repolarization was found to be within the transitional zone
rather than in the FP region.
Optical APs with double
peaks12 were observed within
the AV node or SP zone 3, consistent with a multilayer
conduction
pattern.13 14
Results from one of the experiments are shown in
Figure 2A. The preparation was paced at 800 ms. APs with
relatively early activation were recorded in the superficial layer
of the AV nodal region and correlated with the first peak of the
optical AP. As the microelectrode penetrated 3 to 5 cell layers deeper
(determined by the numbers of cells recorded as the microelectrode
advanced), AV nodal APs with relatively late activation were obtained.
Similar phenomena were also observed in SP zone 3, except that in this
case, only 2 to 3 layers of penetration were required. These findings
indicated that the AV node and SP were covered with a thin layer of
atrial tissue, leading to the development of an early component of
atrial cell activation and a late component of AV nodal cell
activation. The 2 components of activation seen in the optical APs
could be further separated by a premature extrastimulus (A2=200 ms) as
shown in
Figure 2B. Optical APs with secondary derivative signals and
intracellular APs recorded from the FP, transitional zone, and AV
node are superimposed. As the pacing interval decreased, the 2
components of activation in the secondary derivative signals became
more obvious in the AV nodal area. However, optical APs in the FP
remained relatively constant with a single component, indicating that
most of the cell types in the FP were the same. Similar results were
observed in all 6 experiments.
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To further confirm the presence of atrial tissue
covering the AV nodal area, phenol was applied to the AV nodal surface
to destroy the superficial (300 µm)
layers.15 16
Optical APs obtained before and after application of phenol are shown
in
Figure 2C. The tissue was stimulated at 800 ms. A decrease
in atrial electrogram amplitude in the His tracing indicated that
phenol likely destroyed the surface tissue. As the result, the early
activation component in the optical AP was significantly reduced after
phenol application. Phenol significantly prolonged the
stimulus-to-atrium interval from 19.3±2.3 to 28.3±2.0 ms (47%, n=3;
P<0.05) but only slightly
delayed the AH interval from 114.3±4.7 to 118.3±4.9 ms (4%, n=3;
P<0.05), suggesting that
phenol mainly delayed intra-atrial conduction. As the result, the shape
of AVNFCs after phenol application did not differ from those before
phenol application. After applying phenol, it was difficult to obtain
good uniform signals from all sites. Therefore, we were unable to
analyze the conduction sequence after phenol
application.
Our data are consistent the conclusion reached by others17 that the double components of AP were generated by the summation of asynchronously arriving wavefronts from the different layers. Two different optical activation maps have been constructed by using the maximum dV/dt to detect the activation time from the first or the second components.12 13 In the present study, however, we selected the APA-max as the activation time to construct a single optical map. Justifications for adapting this method are described extensively in the online data supplement.
A typical activation map is shown in
Figure 3C. The impulse appeared to be conducted rapidly over
the atrial tissue, and it spread slowly toward the AV node through the
transitional zone. As seen in intracellular recordings,
conduction delay began in the transitional zone. Clearly, atrial
tissues surrounding KT delivered impulses to the AV node, which
strongly suggests that multiple preferential (or nondiscrete) AV nodal
inputs existed. On the basis of the conduction velocities, these inputs
can be arbitrarily divided into FP (192.6±17.4 cm/s; n=6), SP (40.5±5
cm/s; n=6) and intermediate pathway (IP) (78.4±10.2 cm/s; n=6), as
indicated by the arrows in
Figure 3C (ANOVA
P<0.05 between each pathway).
In the presence of an asymmetrical transitional zone,
anterograde conduction over the FP reached the AV node first
because a lesser amount of transitional tissue was involved, whereas
impulses over the IP and SP were relatively slow because activations
propagated through a greater amount of transitional tissue before they
arrived at the AV node. Because the stimulation electrode was placed on
the anterior limbus of the fossa ovalis, atrial tissues were
activated earlier than the FP was activated. Similar
activation maps were obtained in 16 of the 22 preparations. The pattern
of activation sequence did not change at pacing cycle lengths of 400 to
800 ms.
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Delayed activation in SP zone 3 was observed in 6
other experiments. Results from a typical experiment are shown in
Figure 3D-F. Although 3 similar AV nodal input pathways were
observed in the activation map
(Figure 3F), the SP was dissociated; zone 2 showed relatively
normal anterograde conduction, whereas zone 3 showed delayed
activation with double-peaked AP. Not only did these cells look like AV
nodal cells in the microelectrode recording as shown in
Figure 2 and the
Table,
but the activation wavefront came from the AV node region,
consistent with the concept of a posterior extension of AV
node.18 19
Characterization of AV Nodal Reentry:
Slow/Fast Type
AV nodal EBs were induced by atrial programmed
stimulation in 12 preparations (slow/fast, n=8; fast/slow, n=2; and
slow/slow, n=2). Among these, only one exhibited sustained reentrant
tachycardia (slow/fast) of >15 minutes’
duration.
Results obtained from one of the experiments with a
slow/fast EB are summarized in
Figure 4. The AVNFC
(Figure 4A) demonstrated a jump at a coupling interval of 190
ms, suggesting dual AV nodal physiology. Activation maps of A2 obtained
at A1A2 intervals of 350, 200, and 190 ms are shown in
Figure 4B, C, and D, respectively. The activation sequence
of A1 at a basic pacing cycle length of 800 ms (map not shown) was
similar to that shown in
Figure 3C with multiple AV nodal inputs. The activation
patterns of A2 at A1A2 intervals of 210 to 400 ms were similar to the
map shown in
Figure 4B at 350 ms. As the coupling interval decreased,
conduction over the SP gradually slowed. At a further decrease in the
coupling interval from 200 ms to 190 ms, the impulse reached the
refractoriness of the transitional cells, and therefore unidirectional
block occurred at the junction between the FP and the AV node.
Anterograde conduction then shifted from the FP to the SP,
resulting in an abrupt increase (jump) in the AH interval and the
initiation of a slow/fast type of EB. The corresponding optical APs and
EB at an A1A2 interval of 190 ms are illustrated in
Figure 4E and F. The earliest retrograde atrial activation
was recorded in the FP outside KT, consistent with a
slow/fast type of AV nodal reentry. The reentrant circuit was complete
as shown in
Figure 4F. After retrograde atrial activation, the impulse
entered the SP and AV node again with similar sequence but no exit. The
locations of conduction block and earliest retrograde atrial activation
were further identified by optical movies.
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Mapping data from the slow/fast EB indicate anterograde conduction shifting from the FP to the SP, with unidirectional conduction block at the junction between the FP and the AV node, likely caused by the longest APD and refractory periods present within the transitional cells near the AV node. Initial conduction delay within the transitional cells allowed the SP sufficient recovery time, and delay in SP conduction permitted the AV node and FP enough recovery time to be activated again. Anterograde activation from the AV node to the His bundle and retrograde conduction from the AV node to the FP initiated the reentrant EB, which reentered the SP and terminated in the AV node. Atrial tissue located between the FP and SP was part of the reentrant circuit, suggesting that there was no upper common pathway.
Using the criterion of an A2H2 interval duration >50
ms for a 10-ms decrease in the A1A2 coupling interval, the abrupt jump
in the AV node functional curve was observed only in 2 of the 8
experiments with slow/fast type of EBs. In the other 6 preparations,
EBs with similar slow/fast reentrant circuits were induced with no
clear jump. The AV nodal curve from one of these experiments is shown
in
Figure 5A. Selected activation maps at coupling intervals of
300, 220, and 210 ms are shown in
Figure 5B, C, and D, respectively. The activation sequence
of the EB induced at the coupling interval of 210 ms was
consistent with the slow/fast type of reentry. However,
anterograde conduction did not shift abruptly from the FP to
the SP but moved gradually from the FP to the IP
(Figure 4C). With a further decrease in the A1A2 coupling
interval from 220 to 210 ms, anterograde conduction further
shifted from the IP to the SP with an EB but no jump. The IP served as
a bridge to smoothly transfer anterograde conduction from the
FP to the SP during decremental atrial stimulation, resulting in a
smooth AVNFC.
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In 2 preparations, discontinuous AVNFCs were observed without an inducible EB. Anterograde conduction shifted from the FP to the SP but failed to propagate retrogradely to the FP.
Characterization of AV Nodal Reentry:
Fast/Slow Type
Fast/slow AV nodal reentry was seen in only 2 of 12
preparations that had inducible EBs. The activation maps obtained from
both experiments at a pacing cycle length of 800 ms were similar to
that shown in
Figure 3F with delayed SP activation in zone 3. Results
obtained from one of the experiments are shown in
Figure 6. The AVNFC and selected activation maps are shown
in
Figure 6A, B, C, and D. Corresponding optical APs
recorded during EB are shown in
Figure 6E and F. As the pacing coupling interval decreased,
delayed conduction in the AV node and FP became more obvious, as shown
in
Figure 6B and C. At a further decrease in A1A2 coupling
interval to 220 ms, anterograde conduction markedly delayed
within the AV node, resulting in prolongation of A2H2 to 576 ms.
Meanwhile, retrograde conduction slowly propagated through the SP,
allowing the atrial tissue located near the CS ostium to be
activated again as an exit site. The AV node
anterogradely conducted the subsequent EB at a relatively
fast speed with a short AH interval, creating the fast/slow type of AV
nodal reentry. Again, no upper common pathway was present because
atrial tissue located between the FP and SP participated in the
reentrant circuit.
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As shown in
Figure 6A, a classic jump was observed in the AVNFC at an
A1A2 coupling interval of 230 ms. The A2H2 interval abruptly increased
by 261 ms (from 335 ms at A1A2 interval of 240 ms to 596 ms at A1A2
interval of 230 ms). However, anterograde conduction between
coupling intervals of 240 to 220 ms took the same pathway as shown in
the corresponding activation maps in
Figure 6C and D, suggesting that the jump was caused by
conduction delay within the compact AV node rather than by a shifting
of the conduction over another pathway. A similar jump was also seen in
the other preparation with fast/slow reentry.
Characterization of AV Nodal Reentry:
Slow/Slow Type
Slow/slow AV nodal EBs were induced in 2 experiments.
Both preparations exhibited delayed activation in the SP, similar to
the activation map shown in
Figure 3F. Results obtained from one of the experiments are
summarized in
Figure 7. AVNFC and activation maps of A2 at coupling
intervals of 300, 220, and 190 ms are shown in
Figure 7A, B, C, and D, respectively. Optical APs and His
bundle electrogram recorded at 190 ms with an EB are displayed in
Figure 7E and F. As the coupling interval decreased,
anterograde conduction gradually shifted from the FP to the IP,
while retrograde conduction propagated slowly over the SP without exit
(Figure 7C). With a further decrease in the coupling interval
to 190 ms, both anterograde and retrograde conduction
maintained the same pathway, but additional conduction delay in the SP
allowed the adjacent atrial tissue to recover and therefore to be
activated again as an exit site, initiating the slow/slow AV
nodal reentrant beat. The propagation shifting from the FP to the IP
created a smooth AVNFC
(Figure 7A). The slow/slow AV nodal reentrant circuit was
characterized as anterograde conduction over the IP and
retrograde conduction over the SP, with the earliest atrial activation
located near the CS ostium. Like the other 2 types of AV nodal
reentrant EBs, no upper common pathway existed.
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In another experiment, similar slow/slow EBs and sustained tachycardia were induced. The reentrant tachycardia lasted >15 minutes and was terminated by burst rapid atrial pacing. The reentrant circuits and activation sequences of the EBs and tachycardia were identical to a constant tachycardia cycle length (see additional data in the online data supplement).
At the end of the experiments, the SP was selectively interrupted by a surgical incision (slow/fast, n=4; fast/slow, n=2; and slow/slow, n=2). AV nodal reentrant EBs were no longer induced in all preparations.
Discussion
Major Observations
Three Preferential AV Nodal Input
Pathways
Our data suggest that 3 preferential AV nodal
input pathways exist in all normal canine hearts regardless of the
presence or absence of AV nodal EBs. These pathways represent
atrio-nodal connections outside the AV node rather than longitudinal
dissociation within the AV node. At a short coupling interval,
unidirectional block occurs, and these functional pathways can separate
into discrete reentrant pathways for anterograde and retrograde
conduction. These observations are consistent with more recent
data4 suggesting that
multiple AV nodal input pathways might exist because
anterograde AV conduction remains after ablation of both the FP
and the SP.
Absence of Upper Common Pathway
The reentrant circuits for the slow/fast
(counterclockwise) and fast/slow (clockwise) EBs are consistent
with the previous hypothesis5
and identical to those seen in patients with similar types of AVNRT.
The reentrant circuit for the slow/slow EB is different from that
previously proposed.5
However, anterograde conduction actually occurs over the IP and
retrograde conduction over the SP rather than over 2 separate SPs.
Despite different reentrant circuits, atrial tissue surrounding KT is
clearly involved in all 3 types of AV nodal reentry and suggests no
upper common pathway.20 It
is difficult to compare our results to those of a previous
study16 under different
experimental conditions. Taking into account the AV nodal blood supply,
it is likely that the AV node was not totally isolated from atrial
tissue in that study16 ;
otherwise, it would have become ischemic or infarcted in the
setting of a completely dissected KT. Thus, reentry still could have
involved atrial tissue. Recent optical mapping data obtained from
isolated rabbit AV nodal
preparations21 also suggest
that functional AV nodal pathways are located outside the compact AV
node and that AV nodal reentry involves atrial and transitional
cells.
Unidirectional Block in the Transitional
Zone
It is generally believed that in the slow/fast type of
AVNRT, unidirectional block occurs within the FP because of its longer
refractory period. However, our data indicate that the longest APD is
located in the transitional cells, where slow conduction and
unidirectional block occurred during a normal heart rate and
AVNRT.22 The combination of
an asymmetrical transitional zone around the AV node with its posterior
extension and 3 preferential atrio-nodal pathways provide a unique
model for the development of multiple types of
AVNRT.
No Direct Relationship Between AV Nodal Jump
and AV Nodal Input Pathways
Our mapping data indicate the following: (1) An abrupt
jump in the AH interval resulted either from shifting of
anterograde conduction from the FP to the SP or from abrupt
conduction delay within the AV node through the same FP. (2)
Anterograde conduction over the IP smoothed the transition from
the FP to the SP, producing AVNRT with a continuous AVNFC. (3)
Similarly, anterograde conduction over the SP without
retrograde exit can cause a discontinuous AV nodal curve with no
inducible AVNRT.
AV Nodal Posterior Extension
Previous studies have provided evidence to support the
concept of a posterior AV nodal extension and suggested that the
posterior AV nodal extension was involved in slow pathway
conduction.18 19
Our data are compatible with this conclusion and further indicate that
the slow pathway existed in all normal canine hearts and that both
transitional cells and posterior extension of AV nodal cells likely
comprise the cellular substrate of this
structure.
Limitations of the Present Study
Optical mapping is technically limited in that it
cannot reconstruct the 3-dimensional structure of the AV node. The
APA-max method also has several limitations. Questions related to these
limitations are discussed further in the online data
supplement.
Clinical Implications
The new observations in the present study have
several clinical implications. First, the finding that the SP is
involved in all 3 types of reentrant circuit explains the mechanism of
cure by SP ablation applied in patients with various types of AVNRT.
Second, multiple retrograde atrial exit sites will be expected in
atypical AVNRT because retrograde activation conducts from the AV node
to the posterior extension region, where multiple connections exist
between the SP and atrial tissue near the CS. Finally, the FP is not
involved in the reentrant circuit of slow/slow EBs, consistent
with previous findings5 that FP
ablation is not effective in some patients with atypical
AVNRT.
Acknowledgments
Dr Jianyi Wu was supported in part by a Fellowship Award from the North American Society of Pacing and Electrophysiology. This research was also supported in part by grant 9930347Z from American Heart Association. We appreciate the generous help and advice of Dr Igor R. Efimov during the construction of our optical mapping system.
Footnotes
Original received December 27, 2000; revision received April 30, 2001; accepted April 30, 2001.
References
1. Moe GK, Preston JB, Burlington H. Physiologic evidence for a dual A-V transmission system. Circ Res. 1956;4:357–375.
2. Schuilenburg RM, Durrer D. Atrial echo beats in the human heart elicited by induced atrial premature beats. Circulation. 1968;37:680–693.
3. Patterson E, Scherlag BJ. Longitudinal dissociation within the posterior AV nodal input of the rabbit: a substrate for AV nodal reentry. Circulation. 1999;99:143–155.
4. Hirao K, Scherlag BJ, Poty H, Otomo K, Tondo C, Antz M, Patterson E, Jackman WM, Lazzara R. Electrophysiology of the atrio-AV nodal inputs and exits in the normal dog heart: radiofrequency ablation using an epicardial approach [see comments]. J Cardiovasc Electrophysiol. 1997;8:904–915.
5. Otomo K, Wang Z, Lazzara R, Jackman WM. Atrioventricular nodal reentrant tachycardia: electrophysiological characteristics of four forms and implications for the reentrant circuit. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. 3rd ed. Philadelphia, Pa: WB Saunders Co; 2000:504–521.
6. Tai CT, Chen SA, Chiang CE, Lee SH, Wen ZC, Chiou CW, Ueng KC, Chen YJ, Yu WC, Huang JL, Chang MS. Complex electrophysiological characteristics in atrioventricular nodal reentrant tachycardia with continuous atrioventricular node function curves. Circulation. 1997;95:2541–2547.
7. Kim KB, Rodefeld MD, Schuessler RB, Cox JL, Boineau JP. Relationship between local atrial fibrillation interval and refractory period in the isolated canine atrium. Circulation. 1996;94:2961–2967.
8. Biermann M, Rubart M, Moreno A, Wu J, Josiah-Durant A, Zipes DP. Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: implications for optical measurements of cardiac repolarization [see comments]. J Cardiovasc Electrophysiol. 1998;9:1348–1357.
9. Wu J, Biermann M, Rubart M, Zipes DP. Cytochalasin D as excitation-contraction uncoupler for optically mapping action potentials in wedges of ventricular myocardium. J Cardiovasc Electrophysiol. 1998;9:1336–1347.
10. van Capelle FJ, Janse MJ, Varghese PJ, Freud GE, Mater C, Durrer D. Spread of excitation in the atrioventricular node of isolated rabbit hearts studied by multiple microelectrode recording. Circ Res. 1972;31:602–616.
11. Anderson RH, Janse MJ, van Capelle FJ, Billette J, Becker AE, Durrer D. A combined morphological and electrophysiological study of the atrioventricular node of the rabbit heart. Circ Res. 1974;35:909–922.
12. Efimov IR, Fahy GJ, Cheng Y, Van Wagoner DR, Tchou PJ, Mazgalev TN. High-resolution fluorescent imaging does not reveal a distinct atrioventricular nodal anterior input channel (fast pathway) in the rabbit heart during sinus rhythm. J Cardiovasc Electrophysiol. 1997;8:295–306.
13. Efimov IR, Mazgalev TN. High-resolution, three-dimensional fluorescent imaging reveals multilayer conduction pattern in the atrioventricular node [see comments]. Circulation. 1998;98:54–57.
14. Choi BR, Salama G. Optical mapping of atrioventricular node reveals a conduction barrier between atrial and nodal cells. Am J Physiol. 1998;274:H829–H845.
15. Barber MJ, Mueller TM, Davies BG, Zipes DP. Phenol topically applied to canine left ventricular epicardium interrupts sympathetic but not vagal afferents. Circ Res. 1984;55:532–544.
16. Loh P, de Bakker JM, Hocini M, Thibault B, Hauer RN, Janse MJ. Reentrant pathway during ventricular echoes is confined to the atrioventricular node: high-resolution mapping and dissection of the triangle of Koch in isolated, perfused canine hearts. Circulation. 1999;100:1346–1353.
17. de Bakker JM, Loh P, Hocini M, Thibault B, Janse MJ. Double component action potentials in the posterior approach to the atrioventricular node: do they reflect activation delay in the slow pathway? J Am Coll Cardiol. 1999;34:570–577.
18. Inoue S, Becker AE. Posterior extensions of the human compact atrioventricular node: a neglected anatomic feature of potential clinical significance. Circulation. 1998;97:188–193.
19. Medkour D, Becker AE, Khalife K, Billette J. Anatomic and functional characteristics of a slow posterior AV nodal pathway: role in dual-pathway physiology and reentry. Circulation. 1998;98:164–174.
20. McGuire MA, Lau KC, Johnson DC, Richards DA, Uther JB, Ross DL. Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia: evidence that a common pathway of nodal tissue is not present above the reentrant circuit. Circulation. 1991;83:1232–1246.
21. Nikolski V, Efimov IR. Fluorescent imaging of a dual-pathway atrioventricular-nodal conduction system. Circ Res. 2001;88:e23-e30.
22. Mazgalev TN, Tchou PJ. Surface potentials from the region of the atrioventricular node and their relation to dual pathway electrophysiology. Circulation. 2000;101:2110–2117.
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 H. Dobrzynski, V. P. Nikolski, A. T. Sambelashvili, I. D. Greener, M. Yamamoto, M. R. Boyett, and I. R. Efimov Site of Origin and Molecular Substrate of Atrioventricular Junctional Rhythm in the Rabbit Heart Circ. Res., November 28, 2003; 93(11): 1102 - 1110. [Abstract] [Full Text] [PDF]
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 P. Loh, S. Y. Ho, T. Kawara, R. N.W. Hauer, M. J. Janse, G. Breithardt, and J. M.T. de Bakker Reentrant Circuits in the Canine Atrioventricular Node During Atrial and Ventricular Echoes: Electrophysiological and Histological Correlation Circulation, July 15, 2003; 108(2): 231 - 238. [Abstract] [Full Text] [PDF]
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R. Arora, S. Verheule, L. Scott, A. Navarrete, V. Katari, E. Wilson, D. Vaz, and J. E. Olgin Arrhythmogenic Substrate of the Pulmonary Veins Assessed by High-Resolution Optical Mapping Circulation, April 8, 2003; 107(13): 1816 - 1821. [Abstract] [Full Text] [PDF]
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V. P. Nikolski, S. A. Jones, M. K. Lancaster, M. R. Boyett, and I. R. Efimov Cx43 and Dual-Pathway Electrophysiology of the Atrioventricular Node and Atrioventricular Nodal Reentry Circ. Res., March 7, 2003; 92(4): 469 - 475. [Abstract] [Full Text] [PDF]
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Y. Zhang, S. Bharati, K. A. Mowrey, and T. N. Mazgalev His Electrogram Alternans Reveal Dual Atrioventricular Nodal Pathway Conduction During Atrial Fibrillation: The Role of Slow-Pathway Modification Circulation, February 25, 2003; 107(7): 1059 - 1065. [Abstract] [Full Text] [PDF]
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E. Patterson, B. J. Scherlag, H. Yamabe, Y. Shimasaki, O. Honda, Y. Kimura, and Y. Hokamura Demonstration of the Exact Anatomic Tachycardia Circuit in the Fast-Slow Form of Atrioventricular Nodal Reentrant Tachycardia * Response Circulation, April 9, 2002; 105 (14): e80 - e81. [Full Text] [PDF]
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