(Circulation. 1998;97:1613-1622.)
© 1998 American Heart Association, Inc.
Effects of Atrial Defibrillation Shocks on the Ventricles in Isolated Sheep Hearts
Richard A. Gray, PhD;
; José Jalife, MD
From the Department of Pharmacology, SUNY Health Science Center at
Syracuse, NY.
Correspondence to José Jalife, MD, Department of Pharmacology, SUNY Health Science Center at Syracuse, 766 Irving Ave, Syracuse, NY 13210.
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Abstract
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Background—The effects of
cardioversion of atrial fibrillation on the activation sequence of the
ventricles have not been previously studied. In this study we examined
the events in the ventricle that follow the application of atrial
defibrillatory shocks.
Methods and Results—We used video imaging technology to study the
sequence of activation on the surface of the ventricles in the
Langendorff-perfused sheep heart. We recorded transmembrane
potentials simultaneously from over 20 000 sites on the
epicardium before and after biphasic shocks applied by a programmable
atrial defibrillator. The first epicardial activation after the shock
depended on both the voltage and timing of the shock. During
ventricular diastole shocks as low as 10 V
produced ventricular excitation, although the time between
the shock and the first epicardial activation (latency) was 
30 ms.
As the shock voltage was increased to 120 V, latency decreased to zero
and the entire epicardium was depolarized within 30 ms. For 120-V
shocks delivered late in systole, the depolarization sequence produced
by the shock was similar to the previous repolarization sequence.
Shocks of 120 V applied 150 to 300 ms after the previous
ventricular excitation induced ventricular
fibrillation. Ventricular fibrillation was induced by
multiple focal beats after the shock, which produced waves that
propagated but broke down into reentry within regions of high
repolarization gradients.
Conclusions—These results demonstrate that atrial defibrillation
shocks excite the ventricles even at low shock voltages. In addition,
ventricular fibrillation can be induced by shocks given in
the vulnerable period by producing focal patterns that break down into
reentrant waves.
Key Words: cardioversion • defibrillation • fibrillation • ventricles
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Introduction
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Atrial fibrillation
(AF) is the most common sustained cardiac arrhythmia in
clinical practice and, although it is not immediately life-threatening,
increases the risk of stroke.1 Recently, the
possibility of implanting an atrial defibrillator in patients has been
investigated,2 3 4 5 and the effects of
cardioversion of atrial fibrillation have been
studied.6 7 8 9 10 11 12 It appears that the most efficient
means to terminate AF electrically is to apply a biphasic shock with
the duration of each phase equal to 3 ms with the electrode catheters
placed in the right atrium (RA) and the coronary sinus
(CS).11 Although atrial cardioversion can induce
ventricular fibrillation (VF) if the shock is applied
during the T wave, or if the preceding RR interval is
short,9 it appears to be safe if properly
timed.3 5 Some data exist regarding the sequence
of events in the atria after cardioversion of
AF10,11; however, the detailed events in the
ventricle resulting from atrial defibrillation shocks are not known.
However, the effects of electrical shocks on the ventricles have been
extensively studied especially in regards to the initiation of VF and
ventricular defibrillation.13 14
The most extensive study of the sequence of activation during VF
induction resulting from a strong electric field was performed by
Shibata et al.15 They studied the effect of
shocks in dogs with electrodes located on the apex of the left
ventricle (LV) and the right atrium (RA) during atrial and
ventricular pacing. They found that for atrial pacing, when
shocks were applied within a certain interval after the sensed R wave
of the ECG or "vulnerable period," VF ensued. Shibata et
al15 found that the activation sequence in
response to shocks with atrial pacing was complex and sometimes
resulted from a discrete focus and other times resulted from broad wave
fronts propagating away from the border of a region directly excited by
the shock. The patterns resulting from shocks during
ventricular pacing were more simple but were both focal and
reentrant. Although repolarization was not measured in these studies,
the authors presumed that the activation sequence after the shock was
related to the previous recovery sequence. Much earlier, Moe et
al16 found that the first few beats after a
localized shock that induced VF were focal, not reentrant, and
suggested that these beats were essential to the initiation of VF,
which eventually was sustained by reentrant waves. More recently,
studies have shown that the dispersion of repolarization is related to
the induction of VF. Kirchoff et al17 showed that
the dispersion of repolarization measured from seven map
recordings was a better predictor of the vulnerable period than
T-wave parameters from the ECG. In addition, Kuo et
al18 increased repolarization dispersion by using
temperature gradients and demonstrated that there was a critical amount
of dispersion required to induce VF for localized shocks.
The purpose of our study was to investigate the effects of shocks
applied to the heart to terminate AF on the ventricles. We investigated
the sequence of activation on the surface of the ventricles after
atrial defibrillation shocks applied throughout the
ventricular cycle. Because we recorded transmembrane
activity we could record repolarization events before the shock and
relate them to the events after the shock.
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Methods
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Experimental Protocol
Langendorff-Perfused Sheep Heart Preparation
Young sheep of either sex (weight, 16 to 25 kg) were
anesthetized with sodium pentobarbital (35 mg/kg) and the heart
was rapidly removed and connected to a Langendorff system as described
elsewhere.18 Briefly, the coronary
arteries were continuously perfused at a flow rate of 130 to 160 mL/min
with warm (36° to 38°C) Tyrode solution buffered to a pH of 7.4.
The solution consisted of the following (mmol/L): NaCl, 148; KCl, 5.4;
CaCl2, 1.8; MgCl2, 1.0;
NaHCO3, 24;
NaH2PO4, 12; glucose, 5.5.
A bipolar electrogram (EG) was recorded by taking the difference of
two extracellular electrodes placed on the RV and LV near the AV
groove, which allowed us to monitor both atrial and
ventricular activity. We added diacetyl monoxime (DAM) to
the Tyrode solution (10 mmol/L) to stop the heart's contraction.
A bolus injection of 15 mL of the dye di-4-ANEPPS (10 µg/mL)
dissolved in DMSO was injected into the coronary arteries. Two
defibrillation catheters with 6-cm coil electrodes (InControl Inc) were
inserted through the vena cava to the RA and the CS. A custom-made
programmable defibrillator (InControl Inc) was used to deliver a
biphasic shock (duration of each phase was 3 ms). Atrial fibrillation
was induced by burst pacing with a bipolar coaxial electrode placed on
the epicardial surface of the right atrium. Acetylcholine was added to
the Tyrode solution at a concentration of 10-6
mol/L to facilitate the induction of sustained AF.
High-Resolution Optical Mapping
A diagram of the experimental setup is presented in Fig 1A
. The light from two tungsten-halogen
lamps was collimated and bandpass filtered (520±30 nm) together with a
heat filter. A 50-mm objective lens was used to collect the emitted
light. The emitted light was transmitted through a long-pass emission
filter (590 nm) and projected onto a CCD video camera (Cohu 6500).
The video images were acquired with an A/D frame grabber (Epix) at a
rate of 120 frames/s (sampling at 8.33 ms; hereafter referred to as
8-ms sampling intervals). The frame grabber board was mounted on a
Gateway Pentium computer, which was used to process the imaged data.
Recordings were made from various surfaces by rotating the
heart (Fig 1, B through D). Therefore, recordings from multiple
surfaces were not obtained simultaneously.
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Figure 1. Experimental setup. A, The video imaging setup is
composed of a Langendorff-perfused sheep heart, two 250-W light
sources, lenses, a video camera, a frame grabber, a computer, and
excitation (520 nm) and emission (590 nm) filters. The configuration is
described in more detail in the text. B, Posterior view of the heart
with coronary sinus cut open to expose CS coil (black). LV is
to the left of image and RV is on the right with the PDA separating the
ventricles. C, View of RV with the position of RA coil highlighted in
black. D, Anterior view of the heart with RV on the left and LV on the
right of the image separated by the LAD. The position of the CS coil is
shown in black.
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Image and Signal Processing
Signal Processing
To reveal the signal, the background fluorescence was
subtracted from each frame. Low-pass spatial filtering (weighted
average of 7x15 neighboring pixels resulting in a spatial resolution
under 1.5 mm) was applied to improve the signals. The signal (F)
from each site was stretched such that the minimum value from the
episode was 0 and the maximum value was 255 to correct for spatial
nonuniformities in fluorescence intensity. By assuming that
resting membrane potential was -80 mV and the action potential
amplitude was 100 mV, we could approximate transmembrane potential
values (V' in mV) according to the following relationship:
V'=(100/255)*F-80.
Repolarization and Depolarization Maps
Depolarization maps were generated from each time series, F, in
two ways. First, the maximum change in F between two frames was used to
label a wave front. Second, a point in the time plot was labeled as
part of a wave front if F became >160 in that frame (this cutoff
roughly corresponds to a membrane potential of -15 mV). The
depolarization maps for these two methods were the same for paced beats
and the first beat after a shock; however, after shocks that induced
VF, the membrane potential remained elevated and the slope of the
upstrokes decreased in some areas leading to differences between the
two methods. Therefore this cutoff method (F>160) was used to
calculate depolarization maps. The repolarization time (RT) for each
site was calculated as the time when F decreased to <64 (V'<-55 mV,
which corresponds to APD75) after a three-point
moving average temporal filter was applied to F to minimize the effects
of noise on the repolarization tail. Because the iris of the video
camera was open during the entire sampling interval, motion-induced
smearing occurred and therefore a region of pixels perpendicular to the
motion of the depolarization and repolarization processes
activated in a single frame. Thus the depolarization and
repolarization maps are composed of bands, not lines. Note that these
bands derived from video images required no interpolation of data.
Definitions
For clarity, we have defined the following terms: (1)
latency=(time of FEA)-(time of shock), and (2) delay=(time of
shock)-(time of sensed R wave before the shock). In addition, we
classified the heart rhythm after the shock as VF only if >10 rapid
beats occurred.
Statistics
The data are presented as mean value±SD. Comparisons
were performed with the use of individual Student's t
tests.
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Results
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Overview
Hearts from eight sheep were used. After the experiments, the
heart chambers were emptied of solution and the entire hearts were
weighed (187±22 g). After DAM was added to the solution, conduction
from the atria to the ventricle ceased in seven hearts. Therefore, we
inserted an electrode inside the RA and paced the septum near the His
bundle at various BCLs. In the heart in which AV conduction was normal,
we either paced the septum (although we could not capture at large
BCLs) or gave shocks during sinus rhythm. The depolarization sequence
resulting from septal pacing is shown in Fig 2. Isochrone maps of depolarization
from (A) posterior, (B) RV, and (C) anterior surfaces demonstrate rapid
activation of the ventricles. The time of the FEA occurred 25 ms after
septal stimulation at both the base of the posterior surface of the
heart along the LAD (A) and along the borders of the RV including the
RV apex (B). These recordings were not obtained
simultaneously, so differences of <8 ms between panels may
not be significant. The entire surface was depolarized within 75 ms of
stimulation, and the apparent CV measured from the epicardium was
extremely rapid (100 to 400 cm/s). The pattern of depolarization as
well as the rapid depolarization of the ventricles suggest that the
epicardial surface was activated from deeper layers.
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Figure 2. Activation pattern during His bundle
stimulation. Depolarization maps of activation after septal stimulation
at cycle length of 1 second. Views from posterior (A), RV (B), and
anterior surfaces (C). The first epicardial activation occurs 25 ms
after septal stimulation at both the base of the posterior surface of
the heart along the LAD (A) and along the borders of the RV including
the RV apex (B). D, Electrogram demonstrating narrow QRS complexes
indicative of rapid ventricular excitation. The T wave
represents repolarization and the small undulations reflect
AF.
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Effect of Shocks During Diastole
The effect of shocks during diastole were studied by
giving shocks with delay=600 ms. First we studied the effect of shock
voltage on the activation of the ventricles as shown in Fig 3. Isochrone maps illustrate the
depolarization sequence on the posterior surface for various strength
shocks during ventricular diastole: 10 V (A),
20 V (B), 50V (C), and 120 V (D). For the 10-V shock, the time of the
FEA occurred 33 ms after the shock and emerged as a breakthrough
pattern that appeared to propagate across the posterior epicardium. For
shock voltages of 20 to 120 V, the activation patterns were more rapid
with activation from base to apex. However, the time of the FEA
occurred 25 ms after the shock for 20 V, 17 ms after the shock for 50V,
and during the shock for 120 V. For moderate shock voltages (20 to 120
V), the time for total epicardial activation was rapid (33 ms),
indicating transmural propagation. The latency of the first epicardial
activation after the shock was linearly related (P=.0002) to
the voltage of the shock (Fig 3E). The regression relation was
latency=27.85-(shock voltage)/4.195; (n=13, r=-.85).
Shocks with voltages as low as 10 V excited the ventricles apparently
through local activation near the base of the ventricles, but shocks of
20 to 120 V resulted in rapid activation of ventricles via transmural
propagation.
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Figure 3. Effect of shock voltage. Depolarization maps
illustrating the activation pattern on the posterior surface for
various strength shocks during ventricular
diastole: A, 10 V; B, 20 V; C, 50 V; and D, 120 V. For the
10-V shock, the first epicardial activation occurred 33 ms after the
shock as a breakthrough pattern. For shock voltages of 20 to 120 V, the
activation patterns were similar with activation from base to apex,
although the first epicardial activation occurred 25 ms after the shock
for 20 V, 17 ms after the shock for 50 V, and during the shock for 120
V. For moderate shock voltages (20 to 120 V) the time for total
epicardial activation was rapid (33 ms), indicating transmural
propagation. E, Relation between latency and shock voltage. Latency
decreased with increasing shock voltage for shocks given during
diastole and was well fit by linear regression
(P=.0002).
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The sequence of depolarization resulting from 120 V shocks with
delay=600 ms is shown in Fig 4. The FEA
occurs during the shock throughout the heart (white) on posterior (A),
RV (B), and anterior surfaces (C). The depolarization wave breaks
through near the base first although the pattern and rapid activation
(33 ms) indicate transmural propagation. For 120-V shocks, this
occurred during the shock, and the excitation of the ventricles was
extremely rapid and heterogeneous, suggesting that the
shock directly activated a large portion of the ventricle.
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Figure 4. Activation pattern resulting from shocks during
diastole. Depolarization maps of activation after a 120-V
shock with delay=600 ms during septal stimulation at BCL=1000 ms. Views
from A, posterior; B, RV; and C, anterior surfaces. The first
epicardial activation occurs during the shock throughout the heart
(white). The activity breaks through near the base first, although the
activation pattern and rapid activation (33 ms) indicate transmural
propagation. These recordings were not obtained
simultaneously, so differences of <8 ms between panels may
not be significant.
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Repolarization Patterns
The repolarization sequence on the surface of the ventricles was
determined mainly by APD and not the depolarization sequence as shown
by others for the guinea pig19 and the
dog.18 The average APD from the anterior surface
of the heart was 303±27 ms and the dispersion of repolarization
defined as the spatial variance of APD20 was 36
ms2 (BCL=1000 ms). Examples of depolarization and
repolarization sequences resulting from pacing from various sites are
shown in Fig 5. Septal pacing at BCL=1000
ms (A), pacing from RV at BCL=1000 ms (B), and pacing from LV apex at
BCL=1000 ms (C) resulted in varied depolarization patterns. For septal
pacing (A) the FEA occurred at the base of the RV, whereas for
epicardial pacing (B and C), the depolarization wave propagated
uniformly away from the stimulus site. Repolarization was
heterogeneous and was similar for all three stimulation
protocols (bottom). The RV repolarized first with the base recovering
earliest. The latest region to repolarize was low in the LV near the
PDA. The difference in time between the earliest and latest sites to
repolarize was 150 ms.
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Figure 5. Depolarization (top) and repolarization (bottom)
patterns on posterior heart surface. A, septal pacing at BCL=1000ms. B,
Pacing from RV at BCL=1000 ms. C, Pacing from LV apex at BCL=1000 ms.
The depolarization sequence was varied according to the stimulation
site. For septal pacing (A), the epicardial activation occurred at the
base of the RV, whereas for epicardial pacing (B and C) the
depolarization wave propagated uniformly away from the stimulus site.
Repolarization was heterogeneous and was similar for all
three stimulation protocols (bottom). The LV repolarized first, with
the base recovering earliest. The latest region to repolarize was low
in the RV near the PDA. The difference in time between the earliest and
latest sites to repolarize was 150 ms.
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The depolarization sequence after a shock during late systole followed
the previous repolarization pattern, as shown in Fig 6. Repolarization on the LV free wall
resulting from pacing at the LV apex was heterogeneous with
a 100-ms difference between the first and last sites to repolarize (A).
Recordings from three sites with short, medium, and long
repolarization times are shown in B. The sequence of depolarization
after a shock with delay=300 ms followed the previous repolarization
sequence (C). The recordings from three pixels demonstrate that
activation times after a shock were inversely related to the
transmembrane potential preceding the shock and hence directly related
to the repolarization time of the previous beat (D).
Ventricular excitation resulting from the shock was
obscured in the shock artifact in the EG, but the repolarization
sequence in C can be observed shortly after the shock followed by the
next paced beat (E).
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Figure 6. Depolarization pattern after a shock was
determined by previous repolarization pattern. A, Repolarization
pattern on LV free wall resulting from pacing at the LV apex.
Repolarization was heterogeneous, with a 100-ms difference
between the first sites and last sites to repolarize. B,
Recordings from three sites numbered according to the
repolarization times (1 through 3, as indicated in A and C). C,
Isochrone map of the depolarization process after a shock with
delay=300 ms. D, Effect of shock on three sites shown in B. The
sequence of depolarization is such that the first sites that
repolarized were the first to become depolarized after the shock. E,
The electrogram illustrates that the shock was given just past the peak
of the T wave while recovery was still occurring, although the shock
did not induce VF.
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Effect of the Timing of the Shock
When shocks were given shortly after the sensed R wave (delay=20
to 100 ms). VF was not induced, probably because the heart was in its
absolute refractory state. VF was induced at delays=150 to 300 ms,
during the vulnerable period of the ventricles. Shocks given at
delays > 300 ms never induced VF. The data were binned in 50-ms
increments centered at 0, 50, 100, and so on, and the percent induction
of VF versus delay is plotted in Fig 7.
At delays ranging from 230 to 300 ms the shocks sometimes elicited one
to eight extra beats. When > 8 beats were induced, VF was
sustained and defibrillation was required to stop the
arrhythmia.
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Figure 7. Induction of VF versus delay. The percentage of
shocks that induced VF as a function of delay. If the shock was given
20 to 100 ms or >350 ms after the R wave, VF was never induced.
However, if the shocks were delivered 150 to 200 ms after the sensed R
wave, VF was always induced, and if the shocks were 250 to 300 ms after
the shock, VF and extra beats occurred.
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The time of the FEA was a function of the delay at a shock
voltage of 120 V (the data were binned in 50-ms increments and plotted
in Fig 8). Latency is the difference
between datum and the dashed identity line (time of FEA=delay). At long
delays (>300 ms), the time of the FEA occurred during the shock,
therefore latency was equal to zero and the time of the FEA was equal
to the delay. At shorter delays (150 to 300 ms) in which the shock
elicited a response (either one or multiple beats including VF), FEA
occurred after the shock with nonzero latency. The latency decreased
from 131 ms at delay=150 ms to 10.4 ms at delay=300 ms.
Recordings from a site in the LV are shown for a shock given
early during recovery (delay=150 ms) with a long latency (latency=133
ms) and for a shock given late during recovery (delay=300 ms), in which
the FEA occurs during the shock (latency=0 ms).
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Figure 8. Relation between the time of the FEA and delay. A,
FEA occurred during the shock for delay values >300 ms, therefore
these points lie along the identity line indicated by the dashed line
and their latency values were near zero. B, Recording from a
site in the LV when the shock was given at delay=150 ms, in which the
time of the FEA occurred long after the shock (latency=133 ms). C,
Recording from a site in the LV when a shock with delay=300 ms
resulted in an FEA during the shock (ie, latency=0 ms). Both of the
episodes from which these pixel recordings were taken involved
VF induction.
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Induction of Ventricular Fibrillation
The sequence of depolarization after a shock that induced VF was
complex. In general, the first beat after the shock followed the
previous repolarization sequence, as shown in Fig 6
. Fig 9 illustrates the repolarization sequence
of the beat before the shock (1) as well as the depolarization sequence
of the first (2) and second (3) beats after the shock (see the EG at
the bottom for intervals used to construct repolarization and
depolarization maps) from the posterior (A), RV (B), and anterior (C)
surfaces of the heart for a shock (delay=240 ms) that induced VF. There
was very little dispersion of repolarization on the posterior and
anterior surfaces; however, RT occurred earliest on the RV free wall.
The FEA occurred on the anterior surface near the base 8.33 ms after
the shock (asterisk in Fig 9C2). The second beat after the shock first
appeared on the epicardium of the anterior surface 225 ms after the
shock (asterisk in Fig 9C3). There were regions of block on the
anterior surface, but epicardial reentry was not observed in the two
beats after the shock (2 and 3), as indicated by the quiescent interval
between the last activation in the beat after the shock and first
activation in the second beat after the shock (83 ms). These
recordings were not obtained simultaneously, so
care should be taken in comparing columns (A through C). The EG at the
bottom indicates sinus rhythm before the shock and a narrow QRS complex
after the shock before degeneration into VF.
The events occurring on the anterior surface during an episode in which
a shock (delay=250 ms) induced VF are shown in Fig 10; repolarization (A) and
depolarization (B through F) maps were constructed using the time
intervals indicated over the EG at the bottom. The repolarization map
of the beat preceding the shock (A) demonstrates
heterogeneous recovery with early repolarization near the
LAD and late repolarization in the RV and base of the LV. The
depolarization sequence resulting from septal pacing demonstrated rapid
activation of the ventricles (B). The FEA occurred at the apex of the
LV (asterisk) 83 ms after the shock, and the depolarization sequence
after the shock followed the repolarization sequence (C). The
depolarization sequence of the second beat after the shock was similar
to the first beat, with areas of slow conduction that appeared to be
related to regions with large repolarization time gradients (D). Slow
conduction was observed during the first two beats after the shock
along regions of intermediate repolarization separating areas of short
and long repolarization (see A). The first epicardial activation for
the third beat after the shock was at the LV apex as in the previous
beats, but there was also a region that activated early near
the LAD and conducted around the line of conduction block (+) that was
established earlier (see C and D). Shortly thereafter, another
reentrant wave formed (F) also at a region that exhibited intermediate
repolarization values (see A). These reentrant waves occurred at
regions exhibiting large gradients in repolarization times (see A).
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Figure 10. Reentry induction. Repolarization (A) and
depolarization maps (B through F) from the anterior surface for time
intervals indicated at the bottom during an episode in which a shock
with delay=250 ms induced VF. A, Repolarization map of the beat
preceding the shock demonstrated heterogeneous recovery
with early repolarization near the LAD and late repolarization in the
RV and base of the LV. B, Depolarization sequence after pacing the
septum at BCL=1000 ms. The first epicardial activation occurred at the
base of the RV and rapidly completed depolarization of the anterior
surface within 50 ms. C, Depolarization sequence of the first beat
after the shock follows the repolarization sequence. FEA occurred at
the apex of the LV 83 ms after the shock. D, Depolarization sequence of
second beat after the shock was similar to the first beat with areas of
slow conduction that appeared to be related to
heterogeneous repolarization times. E, Depolarization
sequence of third beat after the shock was similar to the first two
beats, but a reentrant wave rotating clockwise (+) formed, resulting
from conduction slowing in the previous two beats. F, A short time
later, another reentrant wave formed at a region of high repolarization
time gradient in the paced beat.
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Our recordings suggest that during VF induction, the
first few beats after the shock do not involve epicardial reentry. To
support this suggestion we calculated a few quantities. If the shock
induced epicardial reentry or reentry developed during the first beat
after the shock, we would expect continuous epicardial activation after
the shock during some of our episodes. Therefore we calculated the time
interval and shortest distance between the last activated
region of the first beat after the shock and the first area to
depolarize in the second beat after the shock. Both these values should
be near zero if epicardial reentry was present but were 148±47 ms
(range, 83 to 242 ms) and 23.4±15 mm, respectively. The interval
between the time of the FEA and the time of the first epicardial
activation during the second beat, which is a rough measure of the
period of the first beat, was 235±26 ms.
Because the ventricular rhythm is irregular during AF, we
speculated that an impulse conducted from the atria during the
vulnerable period of the shock-induced ventricular
excitation repolarization process might induce VF. To test this
hypothesis, we paced the heart at various BCLs while giving a shock at
a fixed delay (600 ms) in three hearts. We varied the BCL in such a way
as to converge (within 1 ms) to the limit of ventricular
excitation. Fig 11 shows a pixel
recordings from two consecutive episodes in which pacing the
septum at BCL=936 ms resulted in excitation of the ventricles 336 ms
after the shock (top), but pacing at BCL=935 ms did not capture the
ventricles 335 ms after the shock (X). Pacing the septum within the
vulnerable period never induced VF but resulted in either a propagated
response or no response. This finding suggests that (1) the
ventricular beat after the shock is unlikely to induce VF
by interacting with the repolarization process of a shock induced
activation, and (2) the shocks given during the vulnerable period
affected a large region of the ventricles that was fundamentally
different than point stimulation.
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Figure 11. Pacing in the vulnerable period. Pixel
recordings from two episodes in which delay was fixed at 600 ms
and BCL was varied. Pacing the septum at BCL=936 ms resulted in
excitation of the ventricles 336 ms after the shock (top), but pacing
at BCL=935 ms did not capture 335 ms after the shock (X). Pacing the
septum within the vulnerable period never induced VF but resulted in
either a propagated response or no response.
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Discussion
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Repolarization
Nonuniform repolarization occurs in the heart as reflected in the
T-wave duration. However, the process of repolarization is not well
characterized, in part because only recently have the techniques become
available to record transmembrane potential from a large number of
sites.19 20 21 In our studies the repolarization
sequence was determined mainly by the APD and not the depolarization
sequence (Fig 5), confirming earlier
studies.18 19 The variance of APD in our studies
was 36 ms2, which is smaller than that reported
for guinea pig hearts.22 The maximum difference
of repolarization times in our studies was 150 ms, considerably
longer than other studies,18 22 which might be
explained by species differences or by the large recording
surface and the large number of recording sites of our
system.
Effects of Shocks on the Ventricle During Diastole
Shocks with voltages as low as 10 V excited the ventricles
apparently through local activation near the base of the ventricles.
This is not surprising, considering the close proximity of the RA and
CS coils to the ventricles. However, the activation did not proceed on
the epicardium as a planar wave, as might be expected, but as a
breakthrough pattern after a delay indicating that the depolarization
wave propagated from the endocardium (Fig 3A). For stronger shocks,
however, a region of the epicardium was directly excited and the time
for complete ventricular excitation was very rapid and the
patterns indicated transmural propagation (Fig 4).
Effect of Timing of the Shock
We found that the time of the FEA was related to delay such that
at short delays there was a lag between the shock and the FEA, whereas
at long delays there was no lag, supporting previous
results.15 16 What happens during the long
latencies for shocks with short delays is not clear. Our data suggest
that this long latency is not due to excitation and slow conduction
velocity on the epicardium. Our data demonstrate that the shock-induced
depolarization sequence was similar to the previous repolarization
sequence (see Figs 6 and 10) when the shocks were given near the
peak of the T wave, which supports the notion that tissue polarization
occurs during the shock but cannot propagate because of surrounding
refractory tissue, which when it becomes excitable allows
propagation.16
Induction of VF
It is well known that stimulating the ventricles during the
vulnerable phase induces VF.23 We found that this
vulnerable phase in our sheep hearts was 150 to 300 ms after the sensed
R wave, which is slightly longer than the range found in dogs (110 to
200 ms)15 and rabbits (182 to 211
ms).24 It is not clear how VF is initiated by
shocks in the vulnerable period; however, the elegant studies of
Shibata et al15 suggest the critical point
hypothesis. By pacing the ventricles and recording the sequence
of activation after a shock during the vulnerable phase, they found
that a pair of counterrotating waves could be formed at certain
reproducible regions in the heart. However, the events after shocks
given during atrial pacing, which presumably had more
heterogenous activation and recovery sequences, were
very complex and were not presented. Our data suggest that for
the electrode configuration we used in the isolated sheep heart, the
first few beats after a shock were focal, although they led to the
initiation of reentrant waves as suggested by Moe et
al16 Our data demonstrate that the reentrant
waves form as the result of waves propagating into regions of
refractoriness. By analyzing the transmembrane potential at various
sites (eg, see Fig 6D and Fig 10), we can speculate about the mechanism
underlying the breakdown to ventricular fibrillation. The
FEA appears in the region that is the most repolarized, and a wave
propagates away from this region but encroaches on increasingly
depolarized tissue. In a region of intermediate repolarization, the
wave slows down and dV/dt decreases. This delay at intermediate
repolarization regions allows the sites with long repolarization times
to recover and when the wave front finally reaches these regions it
propagates similar to near the FEA site. It is possible that these
sites with intermediate repolarization times are at a potential near or
above the sodium current threshold when the wave front reaches this
region. The slow upstroke delays the subsequent repolarization in this
region. Therefore the wave front from the second beat also reaches the
region of intermediate repolarization before the sodium current
recovers. This positive feedback may lead to conduction block in this
region creating the conditions for reentry (see Fig 10, site 2).
Although our data refute the idea that epicardial reentry was induced
by the shock, we cannot rule out that the shock depolarized the
endocardium resulting in transmural reentry. The mechanisms for the
focal beats is unclear, although there is evidence that high-energy
shocks can induce repetitive firing25 26 and
frequently focal patterns occur after ventricular
defibrillation shocks.27
Limitations
Our studies were restricted to one electrode configuration and a
single waveform, therefore the dependence of the results on these
parameters remains unclear. The spatial distribution of APD
and hence the repolarization sequence varied considerably in the
hearts. This variability might have been real; APD distribution has not
been well characterized on the entire heart surface in any species. On
the other hand, APD gradients might have been due to localized
ischemia. TTC staining identifies necrotic regions only and
does not reflect transient ischemia. Extended ischemia
(>5 minutes) seems unlikely because the first sites to repolarize were
the first to depolarize after a shock, suggesting a direct relation
between APD and refractoriness.28 We used the
drug DAM to eliminate motion, which has effects on the heart including
reducing APD.29 We only recorded from the
epicardial surface, although excitation of the deeper layers may have
been important. Recordings from various surfaces of the heart
were not made concurrently, although identical protocols were
accomplished; however, because of the 8-ms sampling interval, episodes
may have been offset in time. The presence of fat on the heart
interfered with the fluorescent recordings and
decreased the quality of signal slightly along the LAD and dramatically
at the AV groove.
|
Selected Abbreviations and Acronyms
|
|---|
| AF |
= |
atrial fibrillation |
| APD |
= |
action potential duration |
| BCL |
= |
basic cycle length |
| CS |
= |
coronary sinus electrode |
| CV |
= |
conduction velocity |
| DAM |
= |
diacetyl monoxime |
| EG |
= |
electrogram |
| F |
= |
fluorescence signal |
| FEA |
= |
first epicardial activation after a shock |
| LAD |
= |
left anterior descending artery |
| LV |
= |
left ventricle |
| PDA |
= |
posterior descending artery |
| RA |
= |
right atrial electrode |
| RT |
= |
repolarization time |
| RV |
= |
right ventricle |
| VF |
= |
ventricular fibrillation |
|
|
Acknowledgments
|
|---|
This work was supported in part by a grant from InControl, Inc.
This work was completed during the Michael Bilitch North American
Society of Pacing and Electrophysiology fellowship awarded to Dr
Gray.
Received July 30, 1997;
revision received October 31, 1997;
accepted November 14, 1997.
|
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Abstract
Introduction