Download Regional Differences in Ventricular Fibrillation in the Open

Regional Differences in Ventricular Fibrillation in the
Open-Chest Porcine Left Ventricle
Kumaraswamy Nanthakumar, Jian Huang, Jack M. Rogers, Philip L. Johnson, Jonathan C. Newton,
Greg P. Walcott, Robert K. Justice, Dennis L. Rollins, William M. Smith, Raymond E. Ideker
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Abstract—It has been hypothesized that during ventricular fibrillation (VF), the fastest activating region, the dominant
domain, contains a stable reentrant circuit called a mother rotor. This hypothesis postulates that the mother rotor spawns
wavefronts that propagate to maintain VF elsewhere and implies that the ratio of wavefronts propagating off a region
to those propagating onto it (propoff/propon) should be ⬎1 for the dominant domain but ⬍1 elsewhere. To test this
prediction in the left ventricular (LV) epicardium of a large animal, most of the LV free wall was mapped with 1008
electrodes in 7 pigs. VF activation rate was faster in the posterior than in the anterior LV (10.0⫾1.3Hz versus
9.3⫾1.3Hz; P⬍0.001). The anterior LV had a higher fraction of wavefronts that blocked than did the posterior LV and
had a propoff/propon ratio ⬍1 (P⬍0.001). The mean conduction velocity vectors of the VF wavefronts pointed in the
direction from the posterior to the anterior LV. Although these findings favor a dominant domain in the posterior LV,
the facts that the anterior LV had a higher incidence of reentry than did the posterior LV and that the posterior LV did
not have propoff/propon significantly different from 1 do not. Thus, quantitative regional differences are present over
the porcine LV epicardium during VF. Although these differences are not totally consistent with the presence of a
dominant domain within the LV free wall, the mean conduction velocity vector is consistent with one in the septum.
(Circ Res. 2002;91:733-740.)
Key Words: ventricular fibrillation 䡲 electrical mapping 䡲 mechanisms of arrhythmias
V
arious hypotheses have been presented to explain the
complex activation sequences during ventricular fibrillation (VF). One hypothesis is drawn from a computer model
of atrial fibrillation where “wandering wavelets” encounter
tissue in which refractoriness is spatially dispersed heterogeneously, leading to reentry that changes pathways from cycle
to cycle.1 Another hypothesis states that instead of the spatial
dispersion of refractoriness, the temporal restitution proportion of refractoriness causes block that sustains VF.2,3 A third
hypothesis is that a single stable dominant rotor, the “mother
rotor,” spawns wavefronts that spread away from it and block
to form complex activation sequences that maintain fibrillation in the rest of the myocardium.4 –9
Recent evidence for the mother rotor hypothesis comes
from studies of optical mapping that imaged isolated rabbit
hearts,6,7 slabs of sheep right ventricular (RV) and left
ventricular (LV),8 and guinea pig hearts.9 This last study
reported that the mother rotor was localized to the anterior LV
epicardium and was responsible for maintaining VF throughout both ventricles. However, others investigating the same
location in the same species did not find evidence of a mother
rotor.10 In the intact swine heart, epicardial reentry also is
uncommon in the anterior LV.11 Optical mapping of slabs of
sheep hearts suggests a mother rotor might be intramural.8
Conversely, optical mapping of the cut transmural surface of
slabs of swine myocardium did not find evidence of a
dominant rotor intramurally.12 However, the cut surface could
have altered the boundary conditions of the tissue, which may
have prevented the formation of an intramural rotor whose
filament terminated on the cut surface.
The mother rotor hypothesis implies that the ratio of
wavefronts that propagate off the region containing the
mother rotor to those that propagate on to it (propoff/propon)
should be ⬎1, but that this ratio should be ⬍1 elsewhere. It
also implies that if the mother rotor is epicardial, the
epicardial region containing the mother rotor should have a
shorter refractory period, a higher VF activation rate, a
greater incidence of reentry during VF, and a smaller amount
of block during VF than the remainder of the ventricles.
Global epicardial recordings from swine have demonstrated
that the basal LV has a higher activation rate than the
remainder of the LV and RV free walls.13 Epicardial mapping
demonstrated that VF wavefronts tend to propagate from the
anterior LV to the anterior RV.14 These findings suggest that
the LV could be the site for a dominant domain in the swine,
if one exists. Therefore, we investigated the LV free wall in
an open-chest model in swine for signs of a dominant domain.
Original received June 7, 2002; revision received September 12, 2002; accepted September 16, 2002.
From the University of Alabama at Birmingham, Birmingham, Ala.
Correspondence to Raymond E. Ideker, MD, PhD, University of Alabama at Birmingham, 1670 University Blvd, B140 Volker Hall, Birmingham, AL
35294-0019. E-mail [email protected]
© 2002 American Heart Association, Inc.
Circulation Research is available at http://www.circresaha.org
DOI: 10.1161/01.RES.0000038945.66661.21
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October 18, 2002
Figure 1. Photograph illustrating anterolateral and
posterior views of an excised heart. Location of
the plaque and the apical defibrillation patch are
superimposed on the photograph. Relevant landmarks are highlighted. x and y axes of the velocity
vector are noted.
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Due to the large number of electrodes needed to cover the
epicardial surface of a large animal heart with sufficiently
close spacing to map the VF activation sequence, exploring
the mother rotor hypothesis with global electrical mapping
has not previously been possible.15 By using 1008 electrodes
on soft plaques that were sutured to the beating heart, we
could map VF activation sequences over 55 cm2 of the LV
epicardium of porcine hearts.
We determined whether differences exist between the
anterior LV and the posterior LV with regard to refractoriness
and during VF with regard to activation rate, propoff/propon,
incidence of reentry, incidence of block, directionality of
wavefronts, and other quantitative characteristics of VF
activation.
Materials and Methods
Animal Preparation and Experimental Setup
The study was approved by the University of Alabama at Birmingham Institutional Animal Care and Use Committee. Seven farm pigs
(University of Alabama at Birmingham Animal Resources Program,
Birmingham, Ala) were anesthetized using 25 mg/kg of intravenous
thiopental sodium, and anesthesia was maintained using Isoflurane in
100% oxygen. Normal metabolic state was maintained by correcting
monitored levels of PO2, pH, base excess, calcium, potassium, carbon
dioxide, and bicarbonate, as needed.
The chest was opened via a left lateral thoracotomy at the 5th
intercostal space. A plaque containing 1008 electrodes (42⫻24
array) was sutured to the beating heart, covering a region from the
posterior descending artery (PDA) to the left anterior descending
coronary artery (LAD) (Figure 1). The plaque covered 55 cm2, which
measurement indicated was about 84% of the left ventricular free
wall. The electrodes in the plaque consisted of chlorodized silver
spheres, 0.75 mm in diameter, with 2-mm interelectrode spacing.
The ground reference for the unipolar recordings was a silver
chloride electrode attached to the chest wall.
Mapping System and Data Acquisition
Two mapping systems were synchronized by a common clock for
time alignment of the two mapping data streams, each recording
simultaneously from 504 of the 1008 electrodes. The unipolar
electrograms were band-pass filtered with a high-pass filter of 0.05
Hz and a low-pass filter of 500 Hz. The data were sampled at 2 kHz
and recorded digitally with 14-bit resolution.16
VF was induced using a 9V battery applied to the base of the LV.
VF was allowed to last 30 seconds before defibrillation. Twenty-five
seconds of data were acquired starting from the induction of VF.
Five episodes of VF were induced per animal. A minimum of 7
minutes was allowed between VF episodes. Each 25 second episode
was analyzed in 5-second epochs.
Quantification of VF
We used analysis algorithms previously developed in our laboratory
for quantifying VF activation patterns.17,18 By grouping together
active samples that were adjacent in space and time, individual
wavefronts were isolated. The overall activation rate was calculated
as the mean number of activations per epicardial recording site per
second.
Collisions and fractionations of wavefronts were identified. A
wavefront remaining after two or more wavefronts collided was
classified as a new wavefront. When localized conduction block
caused a wavefront to fractionate into two or more segments, each
segment was classified as a new wavefront. Events were identified in
which generalized conduction block caused a wavefront to totally
disappear within the mapped region. Events in which a wavefront
first appeared in the plaque at an electrode that was not at the edge
of the plaque and was not as a result of collision or fractionation were
defined as breakthrough. If a wavefront first appeared at one of the
edge electrodes of the plaque, it was deemed to have propagated onto
the plaque (propon) from outside the mapped tissue. If a wavefront
disappeared at an edge electrode of the plaque it was assumed to
have propagated off the plaque (propoff).
We used 0.5-second data segments beginning at each 5-second
epoch to compute the following variables,17,18 which were tabulated
separately for the entire LV free wall mapped, as well as for the
anterior and posterior halves of the LV free wall mapped: (1) total
number of wavefronts; (2) mean activation rate; (3) mean epicardial
area swept out by each wavefront; (4) multiplicity—the number of
distinct activation paths in the VF pattern; (5) repeatability—the
average number of wavefronts that propagated in each of the distinct
pathways; (6) the fraction of wavefronts that collided; (7) the fraction
of wavefronts that fractionated; (8) the fraction of wavefronts that
blocked; and (9) the fraction of wavefronts that broke through.
We also calculated the directionality of VF from the propagation
velocity of each wavefront. The wavefront velocity was estimated by
computing the location of the centroid of the wavefront at each time
sample of the data stream. The velocity of each wavefront centroid
was separated into x and y vector components. The mean weighted
velocity vectors of the wavefronts in the x direction (posterior to
anterior) and y direction (apex to base) were calculated for each
segment as described elsewhere.19
Reentrant Variables
We used the entire 5-second data epoch for the analysis of reentry.
This automated analysis identified and quantified wavefront components that completed at least one cycle of reentry.11 A component
Nanthakumar et al
Organization of VF
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Figure 2. Representative data from a typical
epoch. Data are displayed from an epoch where
the mean activation rate for the anterior half of the
plaque was 9.3 Hz and for the posterior half was
9.7 Hz. A and B, Electrograms of 1-second duration from electrodes in the anterior and posterior
LV. C, Top rectangle represents the 1008 electrode
plaque, with each black square representing an
electrode. A single snapshot in time of activations
is shown at the bottom. Each red pixel is an electrode at which dV/dt was ⬍⫺0.25 V/s. Clusters of
red pixels indicate distinct wavefronts. Larger and
fewer wavefronts are in the anterior LV than the
posterior LV.
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consists of all wavefronts that interact through fractionation or
collisions. Epicardial reentry incidence was defined as the fraction of
components that were reentrant. A network optimization algorithm
was applied to follow the path of the tip of the reentrant circuits to
quantify the mean number of reentrant cycles completed, the mean
perimeter and area circumscribed by the tip of the circuit, and the
mean duration of the reentrant cycles.11,17,18 These variables were
tabulated for the anterior and posterior LV.
Activation Rates
In addition to the mean number of activation fronts passing each
epicardial site per second, we used a second method to assess
activation rate. The fast Fourier transform (FFT) was computed
using Welch’s method on 2-second epochs with 1.024-second
overlapping Hanning windows and 0.5-Hz resolution.20 The peak of
the computed power spectrum was used as an estimate of the mean
activation rate for the tissue beneath each electrode in the anterior
LV and the posterior LV.
Propoff/Propon
The ratio of wavefronts propagating off the plaque to the wavefronts
propagating onto the plaque (propoff/propon) was calculated for the
entire region mapped, as well as for the anterior LV and posterior
LV. We also calculated this ratio for each of the 4 edges of the entire
plaque.
Activation Recovery Interval
To estimate the refractory period throughout the mapped area, the
activation recovery interval (ARI) was calculated at each site.21 ARI
has been shown to be correlated with the effective refractory period.
Statistics
Values are shown as mean⫾95% confidence intervals. Statistical
comparisons were performed using the software package Statview,
SAS Institute. Student’s t test, single group, paired, unpaired, and
standard MANOVA and, if significant, univariate ANOVA were
used as appropriate. Eight nonreentrant VF variables were analyzed
with multivariate and univariate analyses of variance. The variables
were included in a multivariate analysis of variance with factors of
animal, location (anterior versus posterior), VF episode, and epoch.
A complete model with up to 3-way interactions was constructed, to
determine which factors contributed to the overall effect in all of the
variables. Finally, each of the variables was analyzed separately with
a univariate analysis of variance using the same factors as in the final
multivariate model.
An expanded Materials and Methods section can be found in the
online data supplement available at http://www.circresaha.org.
Results
The animals weighed 47.6⫾2.3 kg (mean⫾SD). The hearts
weighed 231⫾22 (mean⫾SD) grams. In total, 175 epochs
from 35 episodes of VF in the 7 animals were analyzed.
Examples of electrograms and a single frame of an activation
map animation are shown in Figure 2. From the multivariate
model, the significant within-animal effects found were
location and epoch. No interactions were significant between
location (anterior and posterior) and epoch, indicating that the
effect of location on the variables was independent of the
effect of VF duration on these variables. Therefore, because
our primary intent was to investigate the effect of location on
VF, results for all epochs are presented together for each
location.
Nonreentrant Variables
The quantitative variables of VF for the anterior and posterior
halves of the mapped region are shown in Figure 3. The
number of wavefronts was higher for the posterior than the
anterior LV (27 versus 34; Figure 3A). The VF activation rate
was significantly higher for the posterior than the anterior
LV, both by counting the number of activations at each
electrode (9.3 versus 10 Hz; Figure 3B) and by FFT analysis
(9.0 versus 9.3 Hz). The area swept out by the wavefronts for
the anterior was greater than the posterior LV (475 versus
425 mm2; Figure 3C). The wavefronts were less complex for
the anterior LV as evidenced by the lower multiplicity index
(4.6 versus 5.7; Figure 3D) and the lower incidence of
fractionation (0.15 versus 0.17; Figure 3G). The incidence of
block was higher for the anterior compared with the posterior
LV (0.26 versus 0.21; Figure 3H). There was no significant
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October 18, 2002
Figure 3. Nonreentrant VF variables for
the anterior and posterior LV. Presented
are the mean⫾95% confidence intervals
for the following: A, number of wavefronts; B, activation rate in Hz based on
dV/dt; C, mean area swept out by each
wavefront in mm2; D, multiplicity; E,
repeatability; F, incidence of collision; G,
incidence of fractionation; H, incidence
of block; and I, incidence of
breakthrough.
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difference between the two regions with regard to the
repeatability index (5.4 versus 5.5; Figure 3E) and the
incidence of wavefront collision (0.16 versus 0.17; Figure 3F)
or of breakthrough (0.24 versus 0.23; Figure 3I).
the duration of a reentrant cycle was longer in the posterior
than the anterior LV (69 versus 74 ms; Figure 4D). Within
animal effects of VF episode and epoch were not considered
for this part of the analysis, because reentrant cycles were not
present in some VF epochs.
Reentrant Variables
Even though the number of wavefronts and the activation rate
were lower in the anterior LV, the incidence of reentry was
significantly higher there than in the posterior LV (0.11
versus 0.08; Figure 4A). The area within (55 versus 68 mm2;
Figure 4B) and the perimeter around (32 versus 36 mm;
Figure 4C) the path of the central tip of the reentrant
wavefronts were significantly higher for the posterior LV
than for the anterior LV. Although there were no significant
differences in the number of reentrant cycles (1.4 versus 1.5),
Directionality of VF
The decomposition of the weighted velocity vectors into x
and y components over the entire mapped region yielded an
x-velocity (parallel to the AV groove from PDA to LAD) of
0.07 m/s, which was significantly different from 0 (Figure
5A). This relationship held true for 6 of the 7 animals (Figure
5B). However the mean weighted y-velocity vector (perpendicular to the AV grove) was not significantly different from
0. There were no significant differences between the anterior
Figure 4. Reentrant VF variables for the
anterior and posterior LV. Presented are
mean⫾95% confidence intervals for the following: A, incidence of reentry; B, area circumscribed by the tip of the reentrant circuit
in mm2; C, perimeter circumscribed by the
tip of the reentrant circuit in mm; and D,
duration of the reentrant cycles in ms.
Nanthakumar et al
Organization of VF
737
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Figure 5. Components of the velocity
vector. A, x-component of the velocity
vector parallel to the AV groove from the
direction of the PDA to the LAD and
y-component of the conduction velocity
vector perpendicular to the AV groove
from the direction of the base to apex
are shown. Presented are the
mean⫾95% confidence intervals in m/s.
B, Mean⫾95% confidence interval in m/s
of the x-component of the conduction
velocity vector are shown for each animal. C, Snapshots of activations in 3 ms
increments are presented illustrating that
overall wavefront direction on the LV epicardium is parallel to the AV groove from
the PDA to the LAD. Data from an epoch
during which the mean x-component of
the velocity vector was 0.07 m/s is illustrated. Black pixel background denotes
the plaque and each different color represents an individual wavefront. Net direction of wavefront movement is from the
right edge of the plaque (the posterior
edge) to the left edge of the plaque (the
anterior edge of the plaque).
and posterior LV with regard to the magnitude and angle of
the velocity vectors. Figure 5C is a series of snapshots of
activation maps illustrating a typical example of wavefronts
propagating primarily parallel to the AV groove from PDA
to LAD.
Propoff/Propon
The propoff/propon ratio for the entire region mapped was
not significantly different from 1 (Figure 6A). The propoff/
propon ratio for the posterior LV was 1.04, which was
significantly higher than for the anterior LV (0.92; Figure
6B). Although the ratio for the anterior LV was significantly
different from 1, the ratio for the posterior was not (Figure
6B). Figures 6C and 6D illustrate the distribution of this ratio
for the anterior LV and posterior LV, respectively. We
correlated the ratio of propoff/propon to possible signatures
of a dominant domain, ie, reentry on the epicardium and
breakthrough to the epicardium. Propoff/propon was not
related to either the incidence of reentry (r2⫽0.001) or the
incidence of epicardial breakthrough (r2⫽0.075).
We also calculated the ratio of the wavefronts that propagated off to those that propagated on for each of the 4 edges
Figure 6. Ratio of wavefronts propagating off to those propagating onto the
mapped region. A, Frequency of propoff/
propon ratios for the entire LV free wall
mapped. B, Mean⫾95% confidence
intervals for the propoff/propon ratios for
the anterior and posterior LV. Whereas
the anterior LV ratio was significantly ⬍1,
the posterior LV ratio was not significantly different from 1. Frequency of
propoff/propon ratios from the anterior
LV (C) and from the posterior LV (D).
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Mother Rotor Hypothesis and Quantitative Differences in VF
Between the Anterior and Posterior LV
Variable
1
F
Multiplicity
1
A
No difference
A
2
A
Area swept out
Collision
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of the plaque individually. The posterior edge of the plaque,
adjacent to the PDA, had a ratio ⬍1, and the anterior edge of
the plaque adjacent to the LAD had a ratio ⬎1. The ratios for
the basal edge adjacent to the AV groove and the apical edge
adjacent to the LV apex were not statistically different from
1 (Figure 7). These observations are consistent with the
directionality of the velocity vector pointing from the PDA to
the LAD and both findings indicate a significant trend for VF
wavefronts to enter the mapped region from the posterior
border of the mapped region and to propagate off the anterior
border.
Activation Recovery Interval
The mean ARI was significantly longer for the anterior than
for the posterior LV (275 versus 268 ms). This finding was
present in all animals except one. There was a significant
correlation between the activation rate by the FFT method
and the mean ARI (r2⫽0.57).
Discussion
This study demonstrates significant differences in quantitative characteristics of epicardial VF activation between the
anterior and posterior LV free walls in open-chest swine. The
posterior LV is able to sustain higher VF rates, and activation
sequences are more complex than in the anterior LV. The
mean velocity vector in the LV is not random, instead it
points from the region of higher activation rate and greater
complexity to the slower region. The incidence of block is
higher in the anterior LV, the region of slower activation. The
faster region, the posterior LV, does not generate more
wavefronts than it receives. Although more wavefronts propagate onto the anterior LV than propagate off it, this region
has the higher incidence of reentry. Moreover, the incidence
of reentry and breakthrough do not correlate with the ratio of
propoff/propon.
Although some of these findings are consistent with a
dominant domain in the LV free wall, specifically the
posterior wall, others are not (Table). The findings are
consistent with at least two possible mechanisms of VF
maintenance: (1) a dominant domain containing a mother
rotor could be located in the interventricular septum or the
posterior RV giving rise to activation fronts that propagate
For or Against a
Dominant Domain
in the LV Free Wall
Activation rate
Repeatability
Figure 7. Propoff/propon ratios for the 4 edges of the entire
mapped region. On average, wavefronts tended to enter from
the posterior edge and leave from the anterior edge.
Mean⫾95% confidence intervals are shown.
Posterior LV
Compared to
Anterior LV
No difference
A
Fractionation
2
A
Reentry
2
A
No difference
A
Breakthrough
Block
Propoff/propon
2
F
1 (but not ⬎1)
A
Quantitative characteristics and how their variability relates to the mother
rotor hypothesis are tabulated. F indicates for a dominant domain in the LV free
wall; A, against.
into the posterior LV and then the anterior LV; and (2)
short-lived reentry circuits and wandering wavelets could be
present throughout all of the ventricular tissue and responsible for VF maintenance, with the activation rate proportional
to the refractory period in each region and with the tendency
for activation fronts in the faster activating regions to spread
into slower activating regions.
Varying Activation Rates Within the Ventricle
The use of FFT analysis to estimate activation rates is
common in the recent literature,7–10 in spite of little validation
of this technique for this purpose.22 A recent publication
points to the dilemma of sacrificing resolution of the FFT to
obtain a single dominant peak and the resultant ambiguity in
using the FFT for describing activation rates.12 Therefore, we
also used the method of identifying activations based on a
dV/dt threshold to estimate the VF activation rate. Both
methods demonstrate a higher global activation rate in the
posterior than the anterior LV. Others have demonstrated an
almost 2-fold difference within the ventricle in the activation
rates of rabbit hearts,7 slabs of sheep RV and LV,6 and guinea
pig hearts.9 This study and a study by Newton et al13
demonstrate only a 7% difference between the fastest and the
slowest activating regions, suggesting that the large regional
differences observed in smaller hearts7–9 may not be present
in larger hearts.
Varying Organization of VF Within the Ventricle
The posterior LV sustains a greater number of wavefronts
than the anterior LV. This finding is related to the findings
that the area swept out by the wavefronts is smaller and the
refractory period is shorter in the posterior than the anterior
LV so that the VF activation rate is faster. VF in the posterior
LV is more complex than in the anterior LV by some
measures, including a higher multiplicity index and fractionation, but not by others, including the number of wavefronts
that follow each activation pathway (repeatability), block
incidence, and collision incidence. Rogers et al14 reported that
VF is slower and is more organized in the RV than the LV,
Nanthakumar et al
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containing fewer, larger wavefronts that follow fewer distinct
pathways and are less likely to fractionate or collide with other
wavefronts. Our data are consistent with the above study in that
the region with the slower activation rate has less complex VF
activation sequences exhibiting fewer, larger wavefronts that are
less likely to fragment. The LV region with the more complex
VF and the higher activation rate also has a lower incidence of
reentry, which argues against the hypothesis that stable epicardial reentry in this region sustains VF.
Our results differ from those of Samie et al9 who reported
that in the isolated, perfused guinea pig heart, the fastest
activating region was in the anterior LV not the posterior LV
and that a dominant domain was present in the anterior LV
giving rise to VF wavefronts that propagated to the remainder
of the ventricular myocardium including the posterior LV.
The differences in the results could have been caused by the
difference in species, the difference in size of the hearts, or
the effects of removing and perfusing the isolated guinea pig
hearts compared with the intact pig hearts that became
ischemic during VF because of the lack of perfusion.
Dominant Domain
The significant differences in propoff/propon, activation rate,
and quantitative characteristics of VF between the anterior
LV and the posterior LV suggest the presence of domains on
the LV epicardium. Chen et al7 used an approach similar to
the propoff/propon ratio to suggest the presence of a dominant domain in rabbit hearts. They analyzed wavefronts
entering and leaving the optical imaging field during episodes
of VF and when a periodic source of wavelets (a rotor or
breakthrough) was present, the number of wavefronts leaving
was greater than the number entering the field. Chen et al
used a model in which the isolated heart was perfused during
VF, whereas our model consisted of the in vivo heart of a
larger mammal that was not perfused during VF so that
ischemia developed. In our pig model, the anterior LV had
more wavefronts propagate onto it than propagate off it.
However, the posterior LV did not have a propoff/propon
ratio significantly ⬎1, suggesting that it merely conducted
and sustained the number of wavefronts that propagated onto
it without housing a mother rotor. This assumption is consistent with our finding that the direction of wavefront propagation is primarily from PDA to LAD. Also the incidence of
reentry and breakthrough did not correlate with the propoff/
propon ratio, which does not support the presence of a
dominant domain in the area mapped, approximately 80% of
the LV epicardial free wall.
Propoff/propon was ⬍1 for the posterior edge of the plaque
and ⬎1 for the anterior edge, suggesting that the net flow of
the wavefronts entered from the posterior edge adjacent to the
posterior septum and exited from the anterior edge. The mean
conduction velocity vector of the wavefronts pointed from the
PDA toward the LAD, which also suggests this conclusion.
Although our observations do not support the dominant
domain hypothesis in the extensive LV epicardial region
mapped, they do not disprove the presence of a dominant
domain in areas not mapped such as the posterior interventricular septum, posterior RV, or intramurally. However, the
epicardial activation rate on the posterior RV has been
Organization of VF
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demonstrated to be slower11 than the LV, and a recent plunge
needle study has demonstrated that the epicardial activation
rate is faster than either the midmyocardial or endocardial
activation rate,23 suggesting that if a mother rotor exists it is
probably in the interventricular septum. This possibility is
supported by the findings of Ikeda et al24 who studied
endocardial activation patterns during VF in the isolated,
perfused canine RV free wall, interventricular septum, and
LV free wall. Greater numbers of wavelets were seen in the
septum than in the RV or LV free walls at baseline, and VF
in the septum displayed a shorter cycle length than in the RV
or LV free walls. A smaller critical mass was required to
maintain VF in the septum than in the RV or LV free walls.
All these findings suggest that the septum is important for VF
maintenance.24
In conclusion, even though the fastest activating portion of
the epicardial surface during VF is the basal half of the LV
free wall, consistent with a dominant domain in this region,13
high-density electrical mapping of the region suggests that, if
a dominant domain exists, it is not in the LV base but may be
in the septum.
If a dominant domain is indeed in the septum, it remains to
be determined why, in the large majority of cases, activation
fronts propagate to the posterior LV free wall but not the
anterior. The reason may be related to the fact that the ARI
estimate of the refractory period in the anterior LV was
significantly longer than in the posterior LV so that conduction block of activation fronts exiting the system may have
been more likely in the anterior than in the posterior direction.
Differences in Refractoriness Within the Ventricle
ARIs have been shown to correlate with refractory periods21
and action potential durations.25 We found that the global
ARI measures for the anterior and posterior LV moderately
correlated with the mean activation rates for the corresponding regions. Although the ARI measurements were made
during sinus rhythm, the hypotension resulting from VF may
have activated cardiac sympathetic efferents that preferentially innervate the posterior LV,26 resulting in further shortening in refractoriness and elevation of activation rate,
especially in the posterior LV during VF. Regional differences in restitution kinetics are another reason that could
potentially explain the differences observed in this study.
Laurita et al27 demonstrated that the restitution slope was
shallower in the RV than in the LV using optical mapping in
the intact guinea pig heart.
Limitations
The region mapped in our study did not include the LV apex.
However, it is unlikely that the apex housed a dominant
domain, as neither the propoff/propon ratio of the apical edge
of the plaque nor the directionality of the conduction velocity
vector of VF was consistent with that possibility. The lack of
mapping data from the septum and transmural region of the
LV free wall is also a limitation, as the analysis performed
could not detect the presence of a mother rotor in those
regions.
740
Circulation Research
October 18, 2002
Acknowledgments
This work was supported by NIH grants HL66256 and HL28429.
K.N. is supported by the clinician scientist program of the Canadian
Institute of Health Research. We would like to thank Dr Cheryl
Killingsworth for expert advice on the experimental setup. We also
acknowledge Kate Sreenan for assistance with manuscript
preparation.
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Regional Differences in Ventricular Fibrillation in the Open-Chest Porcine Left Ventricle
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Circ Res. 2002;91:733-740; originally published online September 26, 2002;
doi: 10.1161/01.RES.0000038945.66661.21
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