(Circulation. 2001;103:1148.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Mechanisms of Resetting Reentrant Circuits in Canine Ventricular Tachycardia
From the Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa (M.S.H.); Departments of Medicine (J.C.) and Pharmacology (A.L.W.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Medicine, Beth Israel Hospital and Thorndike Electrophysiology Laboratory, Harvard Medical School, Boston, Mass (M.E.J.); and Department of Cardiac Electrophysiology, Imperial College School of Medicine and St Mary’s Hospital London, UK (N.S.P.).
Correspondence to Michael S. Hanna, MD, Duncan Building, 301 S 8th St, Philadelphia, PA 19106. E-mail mhanna{at}mail.med.upenn.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Resetting has been used to characterize reentrant circuits causing clinical tachycardias.
Methods and Results—To determine the mechanisms of resetting, sustained ventricular tachycardia was induced in dogs with 4-day-old myocardial infarctions by programmed stimulation. Premature stimulation was accomplished from multiple regions within reentrant circuits; resetting curves were constructed and compared with activation maps. Monotonically increasing responses, or a "mixed" response (increasing portion preceded by a flat portion), occurred. All reentrant circuits had a fully excitable gap. Interval-dependent conduction delay and concealed retrograde penetration led to increased resetting response curves.
Conclusions—Multiple mechanisms revealed by mapping cause resetting of reentrant circuits.
Key Words: reentry • resetting • anisotropy • mapping
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Premature stimulation has been used in clinical studies to characterize reentrant circuits causing ventricular tachycardia.1 2 3 4 5 6 Almendral et al1 noted 3 resetting responses—flat, increasing, and mixed—based on changes in return cycles after progressively premature impulses. They postulated that a flat response indicated a fully excitable gap in the circuit; an increasing response, a partially excitable gap; and a mixed response, a combination of the two. These conclusions are limited by stimulation from outside the reentrant circuit and the inability to map activation to study conduction of the stimulated impulse in the circuit. These limitations do not exist in the canine model of reentrant ventricular tachycardia in which we characterized resetting responses, providing insights for interpreting the resetting response in humans.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Mapping a Canine Model of Myocardial Infarction
We mapped activation in reentrant circuits in the epicardial border zone of 4-day-old canine infarcts during sustained ventricular tachycardias (>30-second duration, monomorphic QRS) induced by programmed stimulation. All methods have been described.7 8
Experimental Protocol
The resetting response was investigated with single
premature stimuli delivered during tachycardia at coupling intervals
(CIs)10 ms less than the tachycardia cycle length and decreased by 10
ms until failure to capture or tachycardia termination. A complete
resetting response was calculated from 5 to 15 premature impulses.
Premature stimuli were triggered from the electrogram near the pacing
site or from the ECG. When possible, resetting protocols were carried
out from different stimulation sites. This involved reinitiation of
tachycardias with the same circuits and QRS morphologies. Cycle lengths
were sometimes slightly different.
Definitions and Statistical Analyses
CIs of electrograms nearest sites of stimulation
(Vnative tach-Vpace)
were plotted against return cycles (RCs), the time from local capture
of this same electrogram to the next beat of the native tachycardia
(Vpace-Vnative tach;
Figure 1
). Resetting resulted in advancement of tachycardia
at both the pacing site and the surface ECG with less than a
compensatory pause: CI+RC<2xcycle length of the native ventricular
tachycardia (VTCL).
|
Simple linear regression was performed on resetting
response relationships with CI as the independent variable and RC as
the dependent variable using the least-squares-fit
method.9 The slope (m) and
intercept (b) of resetting responses were determined, where RC=m(CI)+b.
A resetting response was flat if RC increased <10 ms over a range of
CI of 
30 ms and slope (m) of the CI-RC relationship was
0.33. Increasing responses showed progressive lengthening of
RCs with decreasing CIs with m>0.33; mixed responses exhibited flat
portions at long coupling and increasing responses at shorter
CIs.1 Whether the slope
significantly differed from 0 was assessed by a 2-tailed
t test. The goodness of fit for
each line was evaluated by calculating the coefficient of determination
(r2).
To evaluate for full recovery of excitability in reentrant circuits, resetting was done with minimally premature stimuli, stimulated impulses whose CIs were within 35 ms of the tachycardia cycle length. Because this was not always possible, residual analysis was also used to extrapolate the resetting response to a CI equal to the VTCL (CIvtcl=VTCL). The appropriate CIvtcl, slope, and intercept of each tachycardia were entered into the formula, RCvtcl=m(CIvtcl)+b, graphically equivalent to extending the regression line to the point where it crosses the CI intercept (abscissa), ie, the RC in response to a minimally premature CI (ie, CI=VTCL). The residual (d) was calculated as the difference between the VTCL and RCvtcl: d=VTCL-RCvtcl. A positive or 0 residual indicates full recovery of excitability; negative residuals are associated with lengthened RCs (increasing response).
When resetting was carried out from 2 sites, slopes of
regression lines from each site were compared by use of a modified
t
test.9 When resetting was
carried out from 3 sites, slopes of the resetting response underwent
ANCOVA. If significant, slopes were then compared pair-wise post hoc
with Tukey’s
method.9
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Pattern of Resetting Response Curves
The resetting response depicted in Figure 1A
is plotted in
Figure 1B. A short flat portion occurs (E and F in
Figure 1B) where RCs are equal to VTCLs (216 ms). The
overall response is
"increasing."1 The high
coefficient of determination
(r2=0.971)
indicates a good linear fit.
Data from all experiments are given in
Table 1. Five of the 14 tachycardias revealed a flat
response with late coupled resetting impulses over a range of CIs from
20 to 40 ms (see response 11 in
Figure 1C). These tachycardias demonstrated an increasing
response with earlier premature impulses, an overall mixed response.
Nine of 14 tachycardias demonstrated a monotonically increasing
response over all CIs. No tachycardias had a strictly flat response.
All resetting response slopes were negative and highly significant
(Table 1).
|
A flat portion in the curve has been interpreted as
indicating a fully excitable gap in the reentrant
circuit.1 We assessed other
proposed indicators of a fully excitable gap. Four responses (2, 3, 4,
and 11 in
Table 1) approach unity in their RCs before reaching unity
in their CIs, suggesting full recovery of excitability
(Figure 1C). All 7 tachycardias in which resetting was
carried out with minimally premature stimuli were reset, with RCs equal
to tachycardia cycle lengths suggesting full recovery. The remaining
tachycardias could not be assessed this way. We characterized the
effects of minimally premature resetting stimuli in these and the
previously analyzed 7 tachycardias by residual analysis
(Table 2). All tachycardias with flat portions in their
resetting response or that reset with RCs equal to the tachycardia
cycles have a strongly positive or nearly positive residual (8
tachycardias; residual range, -2 to 45 ms), suggesting full recovery
of excitability. Of the remaining 6 tachycardias, the residual was also
positive or nearly positive in 4 (responses 7, 8, 10, and 14) and
negative to strongly negative in 2 (responses 6 and 13). Damped cycle
length oscillations after resetting with late coupled premature stimuli
did not occur in any tachycardias, also suggesting full recovery of
excitability.10
|
Table 3 shows results of resetting from 2 sites. In 2
experiments (experiments 4 and 5), increasing curves occurred at all
stimulation sites; in 1 experiment (experiment 2), a mixed curve
occurred from both sites. The slopes of the curves from each site were
not significantly different. In 2 experiments (experiments 3 and 6),
the types of curves and their slopes varied with stimulation site; a
flat portion of the curve occurred only at 1 stimulation site and not
the other(s). Slopes of curves from different stimulation sites were
significantly different. In
Figure 1D (experiment 6; 3 sites), the lateral resetting
site yields a flat response and has the steepest slope with earlier
premature stimuli. All regression slopes were significantly different
from each other
(Table 3).
|
Mechanisms of Increasing Resetting
Response
Interval-Dependent Conduction Delay
An interval-dependent conduction delay occurs when a
premature impulse encounters tissue only partially recovered in the
reentrant circuit and conducts more slowly.
Figure 2A shows increasing resetting response curves in 1
experiment. A map of the reentrant circuit during tachycardia (CL, 230
ms) is shown in
Figure 2B. Activation occurs around 2 lines of functional
block parallel to the longitudinal fiber axis. A central common pathway
is between the block
lines.7 8
|
Figure 2C shows activation of a premature impulse delivered
at the pulse symbol (arrow in
Figure 2A; CI, 187 ms, 43 ms premature). The position of the
native tachycardia wavefront at this time is at the dashed line, where
it collides with the antidromic reset wavefront. Isochrones crowd as
activation of the stimulated (reset) wavefront sweeps around the apical
ends of the block lines, arriving at the entrance of the central
pathway 30 ms earlier than during native tachycardia. The reset
wavefront begins activation of the central pathway at 166 ms, 40 ms
late. Activation of this pathway is initially rapid, probably because
of the presence of pseudoblock (small
arrows)7 or contribution from
deeper layers. Conduction through the remainder of the central pathway
is the same as during native tachycardia because of recovery distally
resulting from slower propagation in the proximal pathway. Similarly,
conduction delay increased further with increased prematurity. The
block lines are lengthened, but these changes were not responsible for
the increased conduction delay. The increasing response reflects
interval-dependent conduction delay at discrete points of transverse
conduction; at the entrance to the central pathway, the conduction
pathway is unchanged. This mechanism, noted in all experiments with an
increasing resetting response, was the predominant mechanism in most of
them.
Antidromic Invasion With Concealed Conduction
Delay
Figure 3 shows an example of this mechanism
(Figure 3A; resetting response). During the native
tachycardia
(Figure 3B), 2 reentrant wavefronts rotate around 2 lines of
functional block.
Figure 3C maps the activation of the premature impulse C in
Figure 3A delivered at the pulse symbol near site F (CI, 147
ms, 69 ms premature). At the time of the premature stimulus, the native
wavefront is at the dashed line. Compared with the native tachycardia
(Figure 3B), the block line on the right is shortened by the
stimulated orthodromic impulse, and the central pathway is broader.
Activation also proceeds antidromically, penetrating into the central
pathway between the block lines. The antidromic impulse collides with
the native tachycardia impulse at the solid thin line and thin arrows.
Figure 3D shows activation during the native tachycardia
proceeding from A to H (long arrows). The resetting impulse (pulse
sign) captures near site F (time 0 ms) and propagates orthodromically
(F to A) and antidromically (F to C). Collision of the antidromic
wavefront occurs between B and C: electrograms between F and C are
captured with an antidromic morphology different than during native
tachycardia, whereas morphology at B, distal to the collision site, is
orthodromic. Meanwhile, the orthodromic stimulated wavefront conducts
with interval-dependent conduction delay requiring 100 ms to propagate
around the right line of block (F to A); the native tachycardia
wavefront required only 78 ms. By the time the orthodromically
stimulated wavefront reaches site C, conduction time is 218 ms, equal
to the VTCL, and it is no longer premature. Therefore, the change in
the right line of block did not influence conduction of the premature
impulse. However, the premature impulse continues to exhibit conduction
slowing in the region between sites B and F. Conduction through the
lower portion of the central common pathway is affected by antidromic
invasion with concealed conduction.
Figure 3E shows activation of the central pathway by the
orthodromically propagating stimulated wavefront. The wavefront enters
the pathway at 120 ms, 20 ms later than during the native tachycardia
(
92 to 101 ms); therefore, interval-dependent conduction slowing
through the central pathway is not a factor. Nonetheless, conduction
slows in the region where previously there was antidromic premature
wavefront–native wavefront collision, evidenced by bunched isochrones
between sites B and D. Conduction through the upper end of the pathway
is faster (sites D through F), similar to that of the native
tachycardia (compare with
Figure 3B).
|
Mechanisms of a Flat Resetting Response
Figure 4A is a map of the native reentrant circuit, and
Figure 4B depicts the map of a resetting impulse (CI, 242
ms, 30 ms premature) stimulated at the lateral margin (pulse) during
the flat part of the curve in
Figure 1D (triangles). A dashed line represents the position
of the native reentrant wavefront when the resetting stimulus is
delivered. This wavefront collides with the antidromic stimulated
wavefront (solid line, small arrows). A similar collision with the
second native wavefront occurs at the bottom left (solid line, small
arrows). Meanwhile, the stimulated wavefront penetrates the zone of
slow conduction orthodromically at the entrance of the central pathway.
Activation through this region (isochrones 10 through 90) is no slower
than during the native tachycardia (no interval-dependent conduction
delay). The stimulated wavefront also proceeds throughout the rest of
the circuit without delay, including the region originally activated by
the native tachycardia at the time the premature was delivered, shown
in the inset above
Figure 4B; isochrones do not crowd as the reset wavefront
encounters the region of antidromic collision, despite the wavefront
arriving at this region 30 ms earlier than the native wavefront. Thus,
there is no evidence of interval-dependent conduction delay or
antidromic concealment. The conduction time of the reset wavefront is
equal to that of the native tachycardia. In the electrograms
(Figure 4D), the premature impulse (pulse sign) conducts
without delay; the slope of the arrow is parallel to the slope of the
arrows of the native tachycardia. There is no evidence of antidromic
invasion at site C.
|
in Figure 1D
A map of a more premature stimulus appears in
Figure 4C (CI, 162 ms, 111 ms premature). At this point, the
resetting response is increasing; RC is 357 ms. The native reentrant
wavefront is at the broken line. The stimulated wavefront propagates
further in the antidromic direction than in
Figure 4B before colliding with the native wavefront (solid
line, small arrows). Collision also occurs near the apical margin
(lower left corner). The stimulated wavefront penetrates the central
pathway and slows because of the interval-dependent conduction delay
(bunched isochrones). All of the additional conduction time occurs
within the central pathway. Again, changes in the block line (at the
right) play no major role in the resetting response.
Figure 4E shows that the premature impulse from site D
(pulse) penetrates antidromically to site C, which captures early and
with a different morphology than during native tachycardia. Collision
with the native impulse occurs between sites B and C. The orthodromic
reset wavefront propagates more slowly than during unperturbed
tachycardia; conduction time from D to A increases to 311 ms from 223
ms, accounting for all of the time difference between the RC and the
native tachycardia cycle.
Site-Specific Resetting Responses
Resetting responses from different stimulation sites
were sometimes different
(Tables 2 and 3).
Figure 4 described resetting responses from the lateral
margin in experiment 6
(Figure 1D).
Figure 5A shows a map of resetting from the left anterior
descending coronary artery (LAD) margin (pulse) in this experiment (CI,
188 ms; RC, 318 ms). The native tachycardia wavefront is at the dashed
line. The stimulated wavefront collides with the native wavefront at
the solid thin line (small arrows). Activation proceeds at the right
(sites A to D) with interval-dependent conduction delay, also shown in
Figure 5B. Conduction time from A to D lengthens from 49 to
73 ms. Further interval-dependent conduction delay occurs in the
central pathway; conduction time from D to E increases from 75 to 91
ms. Activation time from site E to A changes little, increasing from
147 to 154 ms. There is no evidence of changes in activation pathway or
concealed conduction delay in the area of antidromic invasion (sites F
to A); the increasing resetting response is due to interval-dependent
conduction delay between sites A and E. As in
Figure 4C and E, the portion of the circuit activated first
by the orthodromic resetting wavefront exhibits the maximal degree of
interval-dependent conduction delay, whereas downstream segments of the
circuit are less affected because of the progressive loss of
prematurity.
|
In
Figure 5C, activation of the circuit by the stimulated
impulse near site F (pulse) (CI, 163 ms; RC, 317 ms) proceeds in the
orthodromic and antidromic directions from within the central pathway.
The native wavefront is at the dashed line; the collision between the
antidromic and native wavefronts is at the solid line and small arrows.
Compared with the native tachycardia
(Figure 4A), there are no major changes in the circuit
pathway. Conduction changes accompanying resetting are shown in
Figure 5D. Activation proceeds in the orthodromic and
antidromic directions from site F, with the former showing
interval-dependent conduction delay, particularly in the region closest
to the pacing site (F to A) where the activation time increases from
112 to 133 ms. Activation times distal to this region do not change.
Concealed conduction delay is not a factor in the increasing resetting
response in this case. Therefore, the center
(Figure 5C) resetting response is increasing because of
interval-dependent conduction delay in the orthodromic region just
proximal to the pacing site.
Taken together, the maps in
Figures 4A through 5D indicate that the presence of proximal
interval-dependent conduction delay is the major factor in the
site-specific resetting response. The lack of such a delay is evident
in a flat response. The differences in slopes of the responses and the
intervals over which resetting occurs appear to arise from
inhomogeneities in conduction and refractoriness at different points in
the circuit and the effects of these inhomogeneities on
restitution.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Resetting Response Curves of Canine Ventricular Tachycardia
The resetting response in this canine model resembles that of clinical ventricular tachycardia associated with previous infarction; flat and increasing responses occurred.1 2 3 4 5 6 Flat portions were short, unlike in clinical responses where flat portions occur over as much as 50% of the cycle.1 This difference may be related to different substrates forming reentrant circuits (discussed below). Although resetting responses in our experiments were predominantly increasing, every experiment revealed evidence of a fully excitable gap8 indicated by (1) convergence of the curves at or before the identity point where the normalized CI equaled the normalized RC, (2) resetting with minimally premature stimuli with an RC equal to the reentrant cycle length, or (3) residual analysis. Damped cycle length oscillations during resetting with late-coupled premature stimuli characteristic of circuits with only a partially excitable gap10 were not observed.
Activation Maps and Resetting
Mechanisms
Maps of flat responses or minimally premature impulses
revealed propagation of the reset wavefront at the same conduction
velocity and reentrant cycle as the native tachycardia, confirming
interpretation of the curves that this model of anisotropic reentry has
a fully excitable
gap.8
All resetting responses had an increasing component. The principle mechanism was interval-dependent conduction delay, progressive slowing of conduction with increasing prematurity.8 10 11 Delay was most pronounced at the turning points around lines of functional block. Thus, when resetting was carried out proximal to such areas, interval-dependent conduction slowing was facilitated. The window of reset also reflected the local excitable gap at the pacing site.8 10 A second mechanism for an increasing response was antidromic concealed conduction, previously only suspected clinically.12 Special circumstances are required for its manifestation. The antidromic wavefront must propagate temporally (not just spatially) for a sufficient time to affect (slow) orthodromic conduction.4 In addition, the wavefront must exhibit sufficient spatial capture to be apparent on the activation map. Stimulation near a site of slow conduction may result in little spatial propagation; thus, the presence of the antidromic wavefront may be difficult to detect. Slow propagation of the orthodromic reset wavefront might then be (incorrectly) ascribed to an interval-dependent conduction delay.
A third possible mechanism proposed to explain clinical resetting is changes in the functional barriers.13 Such changes did not contribute to the increasing resetting response in our experiments.
The underlying heterogeneity of circuit conduction and refractory properties was responsible for site-specific resetting responses, not intervening tissue outside the reentrant circuit between the pacing site and the circuit, as might occur in clinical studies,2 5 12 because the pacing sites were close to or in the circuits. If several regions of the reentrant circuit exhibit interval-dependent conduction delay, then the resetting response is determined by the relationship of the pacing site to these different regions and their respective restitution relationships. Thus, a premature stimulus delivered proximal to a site of interval-dependent conduction delay with a steep restitution response may be slowed sufficiently to arrive relatively late at a second site of interval-dependent delay further downstream. The proximal site will therefore "protect" the distal site and will tend to govern the resetting response. In the converse circumstance, a site of interval-dependent conduction delay with a modest restitution relationship may only partially delay the orthodromic reset wavefront, which will then interact with a downstream region of delay with a steeper restitution relationship, albeit less than if it had not encountered the first region. The interaction of the pacing site and the regions of interval-dependent conduction delay, as well as the restitution relationships, gives rise to this site-specific behavior. Different resetting responses may be elicited clinically from different sites of stimulation, and termination of clinical ventricular tachycardia in response to premature simulation is dependent in part on the steepness of the response.5
Boersma et al11 were unable to demonstrate resetting in a rabbit model of anisotropic reentry and concluded that "it seems very unlikely that clinical tachycardia based on functional reentry can be reset." This disparity with our results reflects differences in the models of reentry that may have important clinical implications for understanding human ventricular tachycardia. In the epicardial border zone of healing infarcts, structural changes influence the properties of the reentrant circuits, particularly the remodeling of gap junctions associated with block lines,8 14 and may be responsible, along with wavefront curvature, for the occurrence of a fully excitable gap.8 Larger anatomical barriers may contribute to the formation of some reentrant circuits causing clinical tachycardia. The variable contribution of anatomic and functional circuit properties may explain different resetting responses among circuits, with the larger fully excitable gaps associated with the more marked structural changes including anatomic reentry.
|
Acknowledgments |
|---|
This work was supported by grants R37 HL-31393 and HL-30557 from the National Heart, Lung and Blood Institute. Dr Hanna is an investigator of the American Heart Association, Southeast Pennsylvania. Dr Peters is an investigator of the British Heart Foundation (RG-2000003).
Received December 31, 1999; revision received August 31, 2000; accepted September 8, 2000.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Almendral JM, Stamato NJ, Rosenthal ME, et al. Resetting response patterns during sustained ventricular tachycardia: relation to the excitable gap. Circulation. 1986;74:722–730.
2. Rosenthal ME, Stamato NJ, Almendral JM, et al. Influence of the site of stimulation on the resetting phenomenon in ventricular tachycardia. Am J Cardiol. 1986;58:970–976.[Medline] [Order article via Infotrieve]
3. Stamato NJ, Frame LH, Rosenthal ME, et al. Procainamide-induced slowing of ventricular tachycardia with insights from analysis of resetting response patterns. Am J Cardiol. 1989;63:1455–1461.[Medline] [Order article via Infotrieve]
4.
Callans DJ,
Hook BG, Josephson ME. Comparison of resetting and entrainment of
uniform sustained ventricular tachycardia: further insights into the
characteristics of the excitable gap.
Circulation. 1993;87:1229–1238.
5.
Gottlieb CD,
Rosenthal ME, Stamato NJ, et al. A quantitative evaluation of
refractoriness within a reentrant circuit during ventricular
tachycardia: relation to termination.
Circulation. 1990;82:1289–1295.
6. Stamato NJ, Rosenthal ME, Almendral JM, et al. The resetting response of ventricular tachycardia to single and double extrastimuli: implications for an excitable gap. Am J Cardiol. 1987;60:596–601.[Medline] [Order article via Infotrieve]
7.
Dillon S, Allessie
MA, Ursell PC, et al. Influences of anisotropic tissue structure on
reentrant circuits in the epicardial border zone of subacute canine
infarcts. Circ Res. 1988;63:182–206.
8.
Peters NS,
Coromilas J, Hanna MS, et al. Characteristics of the temporal and
spatial excitable gap in anisotropic reentrant circuits causing
sustained ventricular tachycardia. Circ
Res. 1998;82:279–293.
9. Zar JH. Biostatistic Analysis. 2nd ed. Englewood Cliffs, NJ: Prentice-Hall; 1984.
10.
Bernstein RC,
Frame LH. Ventricular reentry around a fixed barrier: resetting with
advancement in an in vitro model.
Circulation. 1990;81:267–280.
11.
Boersma L,
Brugada J, Kirchhof C, et al. Mapping of reset of anatomic and
functional reentry in anisotropic rabbit ventricular myocardium.
Circulation. 1994;89:852–862.
12. Josephson ME. Clinical Cardiac Electrophysiology. 2nd ed. Philadelphia, Pa: Lea and Febiger; 1993.
13. Callans DJ, Hook BG, Josephson ME. The mechanism of propafenone-induced slowing of ventricular tachycardia in man as defined by analysis of resetting response patterns. PACE. 1991;14(pt 2):2035–2041.
14.
Peters NS,
Coromilas J, Severs NJ, et al. Disturbed connexin43 gap junction
distribution correlates with the location of reentrant circuits in the
epicardial border zone of healing canine infarcts that cause
ventricular tachycardia.
Circulation. 1997;95:988–996.
This article has been cited by other articles:
 |
|
 |
|
  O. R. Segal, A. W.C. Chow, V. Markides, D. W. Davies, and N. S. Peters Characterization of the Effects of Single Ventricular Extrastimuli on Endocardial Activation in Human Infarct-Related Ventricular Tachycardia J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1315 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. KLEBER and Y. RUDY Basic Mechanisms of Cardiac Impulse Propagation and Associated Arrhythmias Physiol Rev, April 1, 2004; 84(2): 431 - 488. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||