244
Mechanism of Cardiac Defibrillation in
Open-Chest Dogs With Unipolar DC-Coupled
Simultaneous Activation and Shock
Potential Recordings
Francis X. Witkowski, MD, Patricia A. Penkoske, MD, and Robert Plonsey, PhD
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The automatic implantable cardioverter-defibrillator has been shown to dramatically improve
survival. The future refinement of these devices requires a clear understanding of their
mechanism of action. We performed the following study to test two hypotheses: 1) When
defibrillation is successful, fibrillating activity must be annihilated in a critical mass of both
ventricles; and 2) when defibrillation is unsuccessful, at least one area of the ventricular mass
has been left fibrillating. Unipolar AgIAgCI sintered electrodes were directly coupled from
triangular arrays at 40 epicardial locations (total, 120 recording sites) that covered both right
and left ventricular surfaces and were designed to measure the voltage gradient generated by
the shock at each triangular array as well as the underlying myocardial electrical activity before
and immediately after the shock. An algorithm was developed and tested that reliably scored
whether a postshock activation was a continuation of the immediately previous fibrillating
activity. This technique was applied to 203 defibrillation attempts in six open-chest dogs during
electrically induced ventricular fibrillation. There were 139 successful defibrillation attempts
and 64 unsuccessful attempts. Monophasic truncated exponential 10-msec defibrillation
shocks (0.5-35 J) were delivered through an anodal patch on the right atrium and a cathodal
patch on the left ventricular apex. In all cases of unsuccessful defibrillation, at least one
ventricular site could be clearly identified that failed to be defibrillated. In cases of successful
defibrillation two distinct patterns were observed: 1) complete annihilation of fibrillating
activity at all sites or 2) nearly complete cessation of fibrillating activity with a single area of
persistent fibrillation that subsequently self-extinguished within one to three activations. This
single site in the second form of successful defibrillation was located in the region of minimum
voltage gradient produced by the defibrillating waveform and was occasionally accompanied by
dynamic encapsulation with refractory tissue as a result of a wavefront emanating from a region
that had undergone successful defibrillation. These results support the hypothesis that a
critical mass of myocardium must be affected for successful defibrillation and that unsuccessful
defibrillation is always accompanied by residual fibrillating activity in at least one site. The
results also demonstrate that the size of the critical mass required for successful defibrillation
can be less than 100%. (Circulation 1990;82:244-260)
From the Departments of Medicine (F.X.W.), Pediatrics (P.A.P.),
and Surgery (P.A.P.), University of Alberta School of Medicine,
Edmonton, Alberta, Canada, and the Department of Biomedical
Engineering (R.P.), Duke University, Durham, North Carolina.
Supported by grants from the Alberta Heritage Foundation for
Medical Research, the Alberta Heart and Stroke Foundation, and
the National Institutes of Health research grant HL-40609. Performed during F.X.W.'s tenure as a Scholar of the Alberta
Heritage Foundation for Medical Research.
Address for correspondence: Francis X. Witkowski, MD, Division of Cardiology, 2C2.39 Walter MacKenzie Center, University
of Alberta, Edmonton, Alberta, Canada T6G 2R7.
Received September 7, 1989; revision accepted February 27,
1990.
C oronary artery disease is the principal cause of
death in many developed countries, and the
majority of these deaths occur suddenly due
to disturbances in rhythm leading to ventricular fibrillation (VF).1 The only presently successful therapy for
VF is electrical defibrillation. Since the first proposal
by Mirowski et al of the concept of an automatic
implantable defibrillator in 1970,2 this device has been
documented to dramatically reduce the expected mortality of patients with life-threatening arrhythmias,
based on historical control groups.3-5 The future
refinement of these devices requires a clear under-
Witkowski et al Mechanisms of Cardiac Defibrillation
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standing of their mechanism of action in terminating malignant ventricular arrhythmias.
Three mechanisms of defibrillation have been proposed. The "total extinction" hypothesis6 proposes
that all fibrillating activity must be extinguished from
the ventricular myocardium for successful defibrillation to occur. The "critical mass" hypothesis7 suggests that successful defibrillation ensues when a
critical amount of myocardium is rendered incapable
of sustaining VF and that halting of the activation
fronts associated with VF in all regions of both
ventricles is not necessary for successful termination
of VF. The presumed reentrant activity in the myocardium not affected is assumed to be left with a
potential substrate insufficient for self-maintenance.
The "upper limit of vulnerability" hypothesis8-10
suggests that a defibrillation shock of more than 1 J
produces an initial complete cessation of all activation fronts but that after a short latency period, new
activation fronts, also attributed to the initial shock,
emerge to reinitiate subsequent VF.
One of the critical determinants for the effective
differentiation of these potential mechanisms is the
ability to evaluate whether the first postdefibrillating
shock activation is a continuation of the preshock
activity or whether it arises de novo. The elucidation
of the electrophysiological mechanisms underlying
both successful and unsuccessful defibrillation has
been hampered by amplifier saturation induced by
the defibrillation shock that makes the immediate
postshock interval impossible to observe with conventional metallic electrodes tied to AC-coupled amplifiers. One elegant approach to this problem has
involved modification of the mapping system hardware to disconnect the filter sections of the amplifiers
during the shock.8-1"
In addition to observing the underlying myocardial
electrical response to defibrillation, it is essential to
measure the local voltage gradient produced by the
shock to determine the cause of this myocardial
response. The driving force for current flow in the
myocardium is normally proportional to the voltage
gradient imposed.12 One approach to the measurement of the defibrillation voltage gradient has
involved placing many plunge electrodes through the
heart wall, excising the heart, cutting it into slices,
and then digitally reconstructing it.1" This approach
is obviously limited to experimental animals. DC
amplifiers offer several advantages in studies involving defibrillation.13 Such DC amplifiers can recover
rapidly after being saturated by a shock potential,
which when coupled to appropriate nonpolarizable
electrodes with stable DC characteristics14 allow both
the voltage gradient produced by the defibrillating
shock as well as the immediate preshock and postshock activities to be readily visualized.
Whichever of the proposed mechanisms for
defibrillation is correct has clinical significance. The
total extinction hypothesis predicts that the voltage
gradient produced by the defibrillation shock must
achieve some minimal value throughout the ventric-
245
ular mass. The first postshock activation in this
setting could be identified as not being a continuation
of the preshock VF by a pause between the last
preshock activation and the first postshock activation.
The duration of this pause would have to be greater
than the expected interval due to the normal variation of activation intervals present during the preshock VF. The best electrode configuration would be
the one that provides this minimal value of voltage
gradient with the minimal shock energy. In contrast,
the critical mass hypothesis implies that this minimal
value of voltage gradient required for effective
defibrillation must only be achieved in a fraction of
the ventricular mass and that some sites could be
present with a first postshock activation that was a
continuation of the preshock VF. It has clearly been
demonstrated that a critically timed stimulus can
induce a transition into VF from a preceding, moreorganized rhythm such as sinus rhythm, paced
rhythm, and even ventricular tachycardia. To demonstrate de novo induction of VF from a previous
rhythm of sustained VF, as implied by the upper limit
of vulnerability hypothesis, would require demonstration that the first postshock activation in the region of
earliest activation is not a continuation of the previously existing preshock VF. The purpose of our study
was to apply a DC-coupled mapping system to measure both the epicardial voltage gradients produced
by defibrillation and the underlying myocardial electrical activity to test which of the three current
hypotheses for defibrillation is correct.
Methods
Surgical Preparation
Studies were done on six healthy mongrel dogs of
either sex weighing 28-34 kg and anesthetized with
30 mg/kg sodium pentobarbitol administered intravenously and 2-3 mg/kg/hr given as necessary. Each
dog was intubated with a cuffed endotracheal tube
and ventilated with warmed, humidified room air
with supplemental oxygen through a Siemens 900
ventilator with adjustment based on periodic measurements of arterial pH, Pco2, and Po2. Normal
saline was continuously infused at 2 ml/kg/hr
throughout the experiment via the femoral vein, and
systemic blood pressure was monitored via an arterial
line inserted into the femoral artery. In addition to
continuous display of the systemic blood pressure,
surface electrocardiographic leads I and aVF were
monitored on an oscillographic monitor. Body temperature was maintained at 37° C with the warmed
humidified ventilated air, and a heat lamp placed
over the thorax controlled by a YSI 73A temperature
controller (Yellow Springs Instruments, Yellow
Springs, Ohio), with temperature sensed by a thermocouple placed in the midesophagus.
The chest was opened through a median sternotomy, and the heart was suspended in a pericardial
cradle. The aortic root fat pad was dissected free, and
a 4.0-mm Ag/AgCI reference electrode was sutured
246
Circulation Vol 82, No 1, July 1990
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to the aortic root to serve as the reference for all
DC-coupled unipolar recordings. A bipolar pacing
electrode was sutured to the right ventricular
infundibulum for electrical induction of VF. The
anodal titanium mesh defibrillation patch electrode
(modified Medtronics model TX-7 [Promeon Division, Brooklyn Center, Minnesota], reduced to 4.5
cm2) was sutured to the right atrium-superior vena
cava junction. The cathodal defibrillation patch electrode (Medtronics model TX-7, 15 cm2) was sutured
to the left ventricular apex. A nylon mesh sock was
then fitted to the ventricles, and stay sutures were
placed to secure it so it would not slip down from the
atrioventricular groove. The cables for the cathodal
defibrillation patch and the bipolar pacing electrode
were threaded out from under the sock, and the
tripolar Ag/AgCl button electrodes were individually
placed as uniformly as possible over the right and left
ventricular epicardium, carefully avoiding the areas
already covered with the defibrillation patch or the
pacing electrode. A greater density of buttons was
placed over areas of potential interest, such as the
outflow tract of the right ventricle. After all buttons
were placed, the heart was draped with a 4 x 4 in.
sponge pad moistened with warmed saline. The
sternum was approximated and then draped with a
plastic sheet and a towel to maintain the heart in a
moist and constant temperature environment. All
animal procedures conformed to the guiding principles of the Canadian Council on Animal Care.
VF was induced with a train of 2-msec-wide pulses
at twice-diastolic threshold at a pulse repetition rate
of 50 Hz. After 10 seconds of VF, defibrillation was
attempted with a 10-msec monophasic truncated
exponential shock generated by a Medtronics Model
2394 external cardioverter-defibrillator using a 120,uF capacitor with digital leading edge voltage selection from 60-1,000 V. The defibrillation voltage
applied to the patches and the current delivered were
monitored on an oscilloscope for subsequent delivered energy calculations. Approximate defibrillation
voltage thresholds were determined by decrementing
the delivered shocks initially in 100-V increments
until the first shock was unable to defibrillate. The
smallest successful shock was considered the defibrillation threshold. This sequence was repeated three
or four times, and the mean defibrillation voltage
threshold determined. Randomly assigned initial
shocks were then applied in 20-V increments centered around this approximate defibrillation voltage
threshold to cluster the remaining defibrillation
attempts around the defibrillation threshold. In some
animals, 10-V increments were also possible. In an
unsuccessful attempt, defibrillation was obtained
within 5-30 seconds with a higher energy shock
delivered through the same electrode pair. All
defibrillation attempts were included for analysis,
including second shocks after an unsuccessful initial
attempt. A 3-minute interval was observed between
fibrillation episodes.
FIGURE 1. Tripolar Ag/AgCl button electrodes used to
determine the magnitude of the local voltage gradient at the
button produced by a defibrillating shock as well as to observe
the underlying myocardial electrical activity at the three adjacent unipolar recording sites. Actual recording sites are located
at the apexes of an equilateral triangle 3.0 mm on a side. (See
text for fabrication details.)
Tripolar Ag/AgCl Button Electrodes
Sintered Ag/AgCl cylindrical electrodes 0.8 mm in
diameter were made as we have previously described14 and terminated in 0.13-mm (0.005-in.) silver wire. Buttons were machined from 7.9-mm (5/
16-in.) diameter phenolic round rod with a groove for
securing the button into the nylon mesh sock and
with three holes in its central area. The holes were
located at the apexes of an equilateral triangle 3.0
mm on a side into which the Ag/AgCl cylindrical
electrodes were placed as shown in Figure 1. Phenolic was chosen for the button material because of
its superior ability to bond to epoxy. Triangular
geometry was chosen as the minimum number of
sites to determine the voltage gradient in two dimensions and because this configuration ensures stable
contact with all three sites on the epicardium. The
silver wire connected to the Ag/AgCl electrode was
epoxied in place and electrically connected to a
flexible, multiple conductor-shielded cable that had
a crimped stainless-steel strain relief, which was in
turn bonded to the button. After all electrical connections were made and tested, the back of the
button was molded in epoxy. The front side of the
button, which contained the exposed Ag/AgCl electrodes, was polished smooth; then, each electrode
was further machined from its original 0.8 mm diameter to 0.35 mm diameter using a 1.3-mm (3/64-in.)
carbide end mill-machined with a hole in its center.
The cavity around the remaining electrode element
was filled with epoxy and then polished flat. The
Ag/AgCl electrode dimension was reduced to minimize the measurement uncertainty involved in determining accurate voltages with an interelectrode distance of only 3.0 mm and to minimize the extent over
which the electrode would perform its weighted
averaging.15 Each button was initially tested in vitro
in a 40-1 bath with a one-dimensional voltage gradi-
Witkowski et al Mechanisms of Cardiac Defibrillation
ent produced by two square stainless-steel plates
(20x20 cm) connected to a defibrillator.
At the end of each experiment, the heart was
excised after potassium chloride-induced arrest with
the sock and button electrodes in place. Each button
was then replaced with a labeled marker, and the
heart was fixed in 10% formalin.
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Mapping System
The DC-coupled unipolar electrogram signals referenced to the aortic root were amplified, filtered
(DC, 500 Hz), sampled at a 2-KHz rate, and analogto-digitally converted with 12 bits of resolution. Each
of the 120 electrodes were attached to two amplifiers -one with a dynamic range of + 130 mV and the
second of ±500 V. These 240 simultaneously
obtained signals, together with electrocardiographic
surface leads I and aVF, arterial blood pressure, and
defibrillation trigger pulse, were simultaneously digitally recorded as part of a 384-channel simultaneous
mapping system previously described.16 Signal substitution calibration techniques were used for both the
±130-mV and the ±500-V amplifiers.
Every electrogram was individually displayed
together with its derivative and algorithm chosen
activation points, with override capability available
through user-friendly software. Time of activation
(ACT) during VF was determined automatically with
an algorithm based on choosing the maximum negative value of the dV/dt equal to or more than -0.5
V/sec within any 50-msec time interval. For example,
if a peak dV/dt of -5.0 V/sec was found at a relative
time of 50 msec with no dV/dt more negative from
0-50 msec and a peak dV/dt of -7.0 V/sec occurred
at 70 msec (only 20 msec beyond the first suprathreshold event), then only the -7.0 V/sec would be
chosen as an activation if in addition no additional
dV/dt values more negative than -7.0 V/sec in the
70-120-msec window were observed. The search for
activations would then continue anew at 120 msec.
The minimal allowable interval of 50 msec was based
on direct intracellular recordings at the onset of VF
demonstrating an action potential duration of
approximately 50-70 msec.17 This algorithm was first
verified on a training set composed of known continuous VF and found to accurately determine that a
single ACT-ACT interval was a continuation of the
immediately preceding VF in 95% of cases. (See
"Ventricular Fibrillation Characterization" for
details.)
Voltage gradients were determined18 at each button by first obtaining the peak voltage at each of the
three sites. Then, based on the assumption that the
voltage gradient was uniform over the 4.5 mm2 covered by the triangular array, the x and y components
of the voltage gradient were calculated, and the
resultant magnitude was determined. No attempt was
made to orient the buttons uniformly; therefore, the
directional information of the voltage gradient was
lost. In addition to the magnitude of the voltage
gradient at each button, the mean, standard devia-
247
tion, and maximum-to-minimum epicardial ratio
were determined for the entire set of button electrodes for each defibrillation attempt. These were
found useful in assessing the stability and reproducibility of the multiple defibrillation attempts performed within a single animal.
All parameters of interest were displayed on geometrically realistic outlines of the epicardial surface
viewed from the left anterolateral and the right
posterolateral positions obtained from digitized
views of photographs of the fixed heart with button
electrode markers in place.
Data Analysis
The time interval from the last preshock ACT to
the first postshock ACT was expressed as the number
of SDs beyond the mean as measured from the
previous 10 preshock ACT-ACT intervals. (See
"Results" for the experimental justification for this
approach.) A postdefibrillation activation was considered to be a continuation of the previous VF if the
time interval from the last preshock activation to the
first postshock activation was within 2 SDs from the
prior mean ACT-ACT of VF for that site. This
criterion was experimentally verified to correctly classify a continuation of VIF in 95% of cases. An integer
value designating this separation was termed the
standard deviation separation (SDS) and was determined for each recording site for each defibrillation
episode. The mean value from the three sites comprising a single button was termed the button SDS
value. In addition, the activation sequences for at
least the first two postdefibrillation activations were
determined. Thus, 13 activations were determined
for each of 120 sites for 203 defibrillation attempts
for a total in excess of 300,000 activations included in
this study.
Analysis of variance, Scheffe's multiple-range
tests, and general linear model procedures were used
to analyze the differences of grouped means.
Results
In Vitro Measurement Technique Vercfication
Due to the unusual nature of the parameters of
interest needed to test the stated hypotheses,
detailed preliminary evaluation of the amplifiers, the
electrodes, and the analysis schemes were performed
to ensure that no unknown artifacts would be introduced into the desired measurements. Typical unipolar electrogram signals are in the order of 20 mV
peak to peak, whereas the maximum local voltage
induced by a 10-J defibrillating shock is around 200
V, a four order-of-magnitude difference. This is not a
minor local perturbation and can obfuscate accurate
measurements unless specific measures are taken
during the experimental design.
No single amplifier or analog-to-digital converter
combination has the dynamic range to record both
the underlying electrogram signal and the local shock
potential. We used two amplifiers whose inputs were
248
Circulation Vol 82, No 1, July 1990
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FIGURE 2. Panel A: Expeiimental setup used to test that the low-level (±130 mV) DC-coupled electrogram amplifier rccpidly
recovers fiom the direct application of a defibrillating pulse to its input. The oscilloscope output photog:raph shows in waveform a
a 400- Vleading-edge monophazsic truncated exponential pulse and in waveform b the saturated output of the electrogram amplifier.
Of nzote is the retumn to baseline ofwavefonm b within 2-4 msec after the termination of the defibnillatingpulse. The amplified design
is capable ofwithstandingpulses up to 6,500 V without damage. Panel B: Experimental setup used to verify that when thie dyrcamic
range of the DC-coupled amplifier is appropriately extended to ±500 V, a reasonable waveform is provided when the input signal
is a 400-Vleading-edge monophasic truncated exponential as shown in waveform a on the oscilloscope outputphotograph. Ofnote
is the rounding of the leading and trailing edges due to the limited bandwidth of the amplifier as seen in waveform b. (See text for
further details of signal analysis techniques used to overcome these limitations imposed by the use of a 500-Hz bandwidth.)
both connected to the same electrode -one with a
dynamic range of + 130 mV, which is sufficient for
unipolar electrogram evaluation, and a second with a
dynamic range of ±500 V, which was experimentally
determined to be sufficient to record local shock
potentials with leading edge voltages of as much as
1,000 V. The ability of the electrogram amplifier to
withstand such a profound differential signal at its
input and to recover rapidly was evaluated with the
test setup shown in Figure 2A. This figure demonstrates that the low-level amplifier will recover within
2-4 msec after a saturating signal is applied, with the
obvious consequence that no electrogram activity can
be examined for at least 4 msec after defibrillation.
Figure 2B shows the experimental technique used to
demonstrate the ability of the high-level amplifier to
render a faithful if somewhat distorted rendition of
the defibrillation shock voltage, with the leading and
trailing edges slowed down due to the 500-Hz lowpass filtering required to prevent aliasing. Initial tests
documented the linearity of this filtered waveform
with stable and reproducible measurements obtainable by taking a mean value over the center 1.0 msec
of the pulse (three samples, 0.5 msec apart) that
could then be referenced back to the true peak value
by appropriate substitution calibration techniques.
After verifying that the amplifiers were capable of
the intended measurements, the electrodes that
would translate the myocardial voltaic information to
electronic signals were tested. To simulate the simultaneous superimposition of a defibrillatory waveform
of several hundred volts on a 20-mV oscillatory
waveform, the two signals were orthogonally mixed in
a saline bath with the electrodes under test located in
the center of the mixed field in the bath. The
low-level oscillatory waveform used to simulate the
underlying myocardial electrogram activity was
formed by a function generator with a triangular
waveform with a period of 50 msee. If one simply
connects a defibrillator to the output of a signal
generator to couple the signals, the signal generator
is usually destroyed. With such a test setup, the
Witkowski et al Mechanisms of Cardiac Defibrillation
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sintered Ag/AgCI electrodes were tested for their
suitability as shown in Figure 3A, which clearly
demonstrates the ability to observe a continuous
oscillatory waveform immediately after a saturating
pulse has been applied. Also in this figure is shown
the appearance of the same signal recorded in the
simultaneous high-level amplifier, where the underlying oscillatory waveform is buried within the noise
as expected. Defibrillation pulses up to the maximum
produced by our defibrillator (1,000 V) still permitted a clear determination of the underlying low-level
oscillatory waveform. To compare the results
obtained using nonpolarizable electrodes with those
using polarizable electrodes, pure silver electrodes
were also tested as shown in Figure 3B, in which all
waveforms were simultaneously obtained. The
abrupt offset seen with silver electrodes was sufficient
to saturate the low-level amplifiers, eliminating the
ability to clearly see the underlying known continuous oscillatory activity. If a higher-input range was
used to prevent saturation, then signal resolution
would suffer because we are limited to 12 bits of
resolution by the analog-to-digital converters. If the
signal from the silver electrodes is high-pass-filtered
to eliminate the exponential recovery component,
then it could be possible to erroneously conclude that
no signal was present after the shock. For these
reasons, nonpolarizable Ag/AgCl electrodes were
used in this study.
Ventricular Fibrillation Characterization
The ability to differentiate whether the first postdefibrillating shock activation is a continuation of the
preshock activity or whether it represents the beginning of a new stream of events is critical in the
elucidation of the mechanism of defibrillation. The
ACT-ACT interval during VF is irregular, as is the
morphology of the unipolar waveforms. As a consequence, simple template-matching schemes or crosscorrelation determinations cannot be used to classify
a single defibrillation activation waveform. We therefore chose a statistical approach to the problem,
reasoning that over some time interval, the mean
ACT-ACT interval along with its SD should provide
a characterization at a single site that could then be
used to test whether the next activation came from a
similar population. Using a known continuous
recording of VF, we tested what parameters were
needed to state that the last activation in that recording was a continuation of the previous waveform with
a 95% certainty. The time interval over which the
statistics were obtained was not fixed in msec but
rather was fixed in the number of ACT-ACT intervals
to be included. We evaluated averaging intervals of
five, 10, and 20 activations for this purpose as shown
in Figure 4. The time from the second to last
activation (simulating the last preshock activation) to
the last activation (simulating the first postshock
activation) was the interval to be tested. This interval
was given an SDS value of 0 if it was more than 1 SD
below the mean and less than or equal to the mean
249
value, a value of 1 if it was less than or equal to the
mean plus 1 SD but greater than the mean, and so
on. We counted the number of times each of the SDS
values were found in a test set formed of 50 unipolar
recordings from two runs of continuous VF in three
dogs for a total of 6,600 activations analyzed. The
results of this analysis are shown in Table 1 and
demonstrate that scoring a single activation correctly
as being a continuation of VF using a 10-beat average and an SDS of less than or equal to 2 gave a
correct result close to the desired 95% accuracy. In
other words, 95% of the values for ACT-ACT during
VF occurred within 2 SDs from the mean when a 10
or greater activation averaging window is chosen. We
chose to use 10 activations because the classification
was slightly tighter than for five beats and because it
provides the same classification accuracy as if 20
beats were examined but requires one half the analysis time. Therefore, in this study in testing the first
postdefibrillating activation, the mean and SD of the
10 preshock ACT-ACT intervals are used to calculate the SDS value for that activation. The value
assigned to a button location was the mean SDS
value for the three sites present on each button
rounded up to the next highest integer and was
termed the button SDS value.
Interestingly, a defibrillation shock may occur synchronous with an activation in a region that is unaffected by the shock, but then the first postshock
activation would be assigned a high SDS value because
the last preshock activation would have been masked.
To address this possibility, we reasoned that three
closely placed unipolar electrodes would observe similar waveform morphologies but would have slightly
different activation times; therefore, the probability
that the shock would mask the last preshock activation
in all three would be reduced. For this reason and for
the calculation of the local voltage gradient, a tripolar
button electrode design was used in this study.
Reproducibility and Stability of Shock Field and
Underlying Ventricular Fibrtillation
Before examining the mechanisms involved in
defibrillation, the reproducibility of defibrillating
field generation and measurement was addressed as
well as the reproducibility of VF from episode to
episode. The stability and reproducibility of the
defibrillator and the resulting voltage gradient field
produced are demonstrated by the values in Figure 5
for a single representative dog. The mean value of
the voltage gradient for each defibrillation episode
averaged over all the button electrodes on the heart
was found to be linearly related to the applied
leading edge voltage. Furthermore, the fields were
reproducible as shown for two leading edge voltage
values in Figure 5, and the stability of the preparation
over the 30 defibrillation episodes in this animal is
documented by the stability of the maximumto-minimum-voltage-gradient ratio, which should be
independent of leading edge voltage within the
ranges used.
Circulation Vol 82, No 1, July 1990
250
A
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10 V
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Defbrlatory piise:
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Defbriatory p
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FIGURE 3. Panel A: Results obtained in vitro with orthogonally mixed low- and high-level signals used to simulate simultaneous
underlying myocardial extracellular electrograms and the defibrillation pulse when the recording electrodes are made of sintered
Ag/AgCl. In a, the pulse from the defibrillator was set to the minimum setting, and the underlying low-level triangular waveforn is
readily visualized immediately after the shock The same electrodes are simultaneously connected to a 500-V amplifier, and its
output is shown in b and documents a 13-Vlocal difference. c demonstrates with the maximal defibrillator setting, independent of
polarity, that the underlying triangular waveform is faithfully recorded. The slight increase in amplitude after the shock in c was
documented to be an artifact produced by feedback modulation of the waveform generator by the shock-induced signal present on
the recording electrodes and therefore not an artifact generated by either the recording electrodes or the DC amplifiers. In d is the
companion high-level (±500 V) amplifier output for the higher-level shock. Panel B: Results obtained in vitro with the same
experimental setup when two pairs of recording electrodes separated by 1 mm are used, with one pair composed of nonpolarizable
AgIAgCl in a and b and of polarizable Ag in c and d. The waveforms at the same defibrillating shock setting were obtained
simultaneously with identical amplifiers. The triangular waveform in a is clearly visualized after the shock; but the identical
defibrillatingfield creates a much larger offset potential in the DC-coupledAg electrode recordings in c with the subsequent inability
to visualize the known continuous electrical activity that was present. This offset seen with polarizable electrodes becomes more
profound as the shock field is increased as shown in d. The voltage level adjacent to the defibrillating pulse artifact in each panel
is the companion high-level amplifier-recorded voltage difference documenting the ability of metallic polarizable electrodes to
provide similar high-level voltaic information as their nonpolarizable counterparts.
-
Witkowski et al Mechanisms of Cardiac Defibrillation
251
VF CLASSIFICATION ALGORITHM VERIFICATION
FIGURE 4. Example of a single unipolar recording during continuous ventricACT-ACT INTERVAL TO BE EXAMINED
ularfibrillation (VF) used to test the VF
.-1n] 1- 107.5 msec
categortization algorithm developed. The
3 4 5
7
same waveform is shown in all three
ACT-ACT MEAN S.D.
panels, with progressively longer examination windows chosen. In all 3 cases,
112.4
6.66 the last time of activation (ACT)-ACT
interval is the interval to be characterized
as to whether it is a continuation of the
5 BEAT AVERAGE +
prior waveform. In the three panels are
shown the activations chosen together
& 9 10 11 12
with the mean and SD for that averaging
interval. In this case, the ACT-ACT to be
examined is less than the mean value but
114.8
7.04 greater than 1 SD below the mean for the
five and 20 activation averages and
would be assigned a standard deviation
+
separation (SDS) value of O for these two
200 msec
evaluations and an SDS value of -1 for
1 2
4
I 19 20 21 22
the 10-beat average because the ACTACT to be examined for that evaluation
lies between 2 and 1 SDs below the
a
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
GE
V,//V
20 mV
112.8
6.98
mean.
ttl
+
20 BEAT AVERAGE
The stability of the VF induced before the multiple
defibrillation trials was also examined for reproducibility as shown in Figure 6 for the same representative animal used in Figure 5. Figure 6 demonstrates that the mean ACT-ACT interval over both
ventricles of the 10 activation intervals before the
defibrillation shock were acceptably reproducible
over the 30 trials examined. Additionally, the mean
dV/dt value for the 10 activations before the shock
averaged over both ventricles provided a remarkably
reproducible value for each defibrillation attempt.
buttons demonstrated a button SDS value of 3 or
more at each site. Of the 139 successful defibrillation
attempts analyzed, this form of defibrillation was
observed in 116 (83%). The locations of the first two
postshock activations were varied for this form of
successful defibrillation, with the majority located at
buttons adjacent to the cathodal defibrillation patch.
Figures 7 and 8 contain a typical example of this form
of defibrillation for a 13-J defibrillation shock. In
Figure 7 are displayed the epicardial voltage gradients generated by the defibrillation shock and the
activation sequence of the first postshock activation.
The button SDS values are included in the first
postshock activation map and document that no sites
were left fibrillating on the heart; therefore, the first
postshock activation was initiated by a different
Successful Defibrillation With Immediate Complete
Ventricular Fibrillation Termination
Immediate complete cessation of VF was established when the first postshock activation from all
TABLE 1. Cumulative Percentage of Successful Scoring of a Single Activation of Ventricular Fibrillation for Prior
Activation Counts of Five, 10, and 20 Activations
Prior averaging
window length
<Mean
<Mean + 1 SD
<Mean + 2 SD
<Mean + 3 SD
5 activations
43±+6
79±4
91±5
94+3
10 activations
47±7
*I
*
83±2
It
20 activations
46±9
All values are given as mean±SD.
*Significant at p<0.05.
85±2
II
94±2
_______
NS
~~~~
95±2
-
97±3
~~NS
NS
98±4
NS
Circulation Vol 82, No 1, July 1990
252
#10589
#10589
0
tI y=~ ~ ~ y 0.041 x -0.458
,
1
U)
Correbtion Coeff.= 0.99
.
.
...........
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............................................
1-
...................
.0
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.............................................. ..............
200
100
300
400
500
600
8
700
Defibriltion Shock Leading Edge Vdtoge Cvlalt)
LC)
D
KY _t
1
5
10
15
20
25
30
6
Defibrillation Attempt Number
4N=1
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...........:..........
...........
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Leading Edge Vo/toge =400
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5
10
s15
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0
o
30
c
Defibritation Attenpt
10
15
20
25
Defibrillation Attempt Number
FIGURE 6. Representative data (for the same animal as
Figure 5) that demonstrates in the upper panel the relative
stability of the activation intervals of the lOpreshock activations
during ventricularfibrillation (VF) averaged over both ventricles
from all recording sites for each of the 30 defibrillation attempts.
Values are given mean ±SD. Lower panel: Similarly derived
values for the dVldt for these same activations.
8
..............
0
...................................
40).
*
0 0
a0
0
......................1
.
.S.... W
q
.
--L.
-
.............................................
.....................
mechanism. In this case, the first postshock activation
,0
arose from a site near the cathodal defibrillating
~~~~
Wo
30
from
15
20
25
35
Defibrilotion Attempt Number
FIGURE 5. Representative data from a single animal demonstrating the linearity, reproducibility, and stability of the
experimental preparation and the measurement technique.
Top panel: Voltage gradients averaged over both ventricles
for each defibrillation attempt as a function of the leadingedge voltage demonstrating the linear relation between the
field produced and the defibrillating shock level. Leadingedge voltages of 200-500 V correspond to delivered energies
of 2-13 J. Middle panel: Voltage gradients averaged over
both ventricles for two different leading-edge voltages, which
were randomly dispersed throughout the total of 30 attempts,
with the results for the attempts examined grouped together
for clarity. There were nine attempts at a 400-V leading-edge
voltage and five attempts at 200 V and the means and SDs
are shown for each attempt, demonstrating their reproducibility. Bottom panel: Ratios of the maximum and the
minimum epicardial voltage gradients found in each of the
30 defibrillation attempts in this animal, which document
their stability.
the
patch. Of note in the electrogram recording
earliest site indicated by an asterisk in Figure 7 and
displayed in Figure 8 is the initiation of an electrogram with an initial QS deflection in the first postshock activation consistent with the observation that
this site is near the origin of this activation wavefront.
The mathematically calculated dV/dt is also displayed,
without smoothing, and documents the relatively
unambiguous appearance of points chosen for activation. Furthermore, the earliest site for the first postshock activation is clearly seen to change morphology
by the second postshock activation, which indeed was
mapped to a site near recording site B, which for its
second postshock activation now demonstrates an
initial QS wave. The unipolar recording technique
thus provides additional qualitative information that is
helpful in activation sequence determination in addition to clear indications of local activation.
Unsuccessful Defibrillation
A total of 64 episodes of unsuccessful defibrillation
were examined. When a defibrillation attempt was
Witkowski et al Mechanisms of Cardiac Defibrillation
253
#10589, Episode 2, 500 V/10 msec
VOLTAGE GRADIENT MAP
RV
RV
Mean Global Voltage Gradient = 21.9 ± 10.5 V/cm
Minimum Voltage Gradient = 8.7 V/cm
Maximum Voltage Gradient = 58.5 V/cm
Ratio of Max/Min = 6.7
Right postero-lateral view
Left antero-lateral view
F
1st POST-SHOCK ACTIVATION MAP
RV
73.01 7*
(and accompanying SDS VALUES)
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
Total Epicardial Activation Time
=
78.5
600
48.5a
msec
D
LV
520
*44.512
40".31. 441.
Mean Global SDS value = 10.5 ± 4.2
Mimimum Button SDS value = 5
064.5 12On
*68u15j*6s.O
48.515
22.5
6
40
*30o.s
LV
72.5
*. 68.5
0W
~~~~62.SW
E
36
28.W
RV
isW 730
.
*48.59
48.5
n15
35
t vB
>
B j
A
Left antero-lateral view
Right postero-latercil view
FIGURE 7. Successful defibrillation - total ventricular fibrillation (VF) termination type. Upper panel: Typical voltage gradient
map from dog 10589 for a successful defibrillation shock where all epicardial sites were documented to have had their preshock
VF terminated. Stippled areas represent the cathodal defibrillation patch electrode. Solid circles on heart outlines represent locations
of the 40 button electrodes, each with three recording sites. Upper panel: Number next to the button location is the voltage gradient
value at that button (V/cm). For clarity, only the 10, 15, and 20 V/cm isovoltage gradient contour lines are drawn. Lower panel:
Number next to the button location is the time (msec) of the minimum value found for that button for the first postdefibrillation
activation relative to the earliest measured activation. The total epicardial activation time is the difference between the maximum
and minimum times found from all 120 sites. Immediately adjacent to the activation time, surrounded by a small box, is the mean
standard deviation separation (SDS) value deternined for that button, calculated from the three recordings found on that button
(terned the "button SDS value"). The minimum button SDS value for this defibrillation episode was 5. The site of earliest
activation, 0.0 msec (192 msec relative to the last preshock activation at that site), is indicated by an asterisk and six other sites
are noted by curved arrows and labeled A-F. Isochrones are drawn in 20-msec steps. Site D occurs slightly earlier than would be
expected by simple propagation from the earliest site and thus probably represents a fusion from a wavefront rapidly conducted over
the Purkinje network. Site D is near the site of right ventricular breakthrough during sinus rhythm. (See Figure 8for the electrograms
found at the earliest site and the six other sites.) LV, left ventricle; RV right ventricle. Values are given as mean ±SD.
unsuccessful, at least one site was always found in
which first postshock activation was judged to be a
continuation of the previous fibrillating activity based
on an SDS value of 2 or less. For the cathodal
defibrillating patch located on the left ventricular
apex, which produced a minimum voltage gradient
near the base of the heart and the right ventricular
outflow tract, the residual fibrillating activity originated predominantly from these locations for
defibrillation shock levels near defibrillation threshold. For leading edge voltage levels 100 or 200 V
lower, the voltage gradients followed a similar distribution, but sites of continuing fibrillation were more
scattered throughout the ventricles. If 2 or more
different noncontiguous sites were recorded after the
shock to be still fibrillating, then defibrillation was
unsuccessful in 100% of the cases. As the leading
edge voltage was further reduced below levels that
yielded defibrillation success percentages of less than
25%, the effect was to further reduce the percent
success and to observe additional sites with SDS
values less than or equal to 2. An example of a
representative unsuccessful defibrillation with multiple contiguous sites left fibrillating is shown in Figures 9 and 10 for a 5 -J shock. In Figure 9 are the
voltage gradients produced by the shock and the
activation sequence of the first postshock activation.
In Figure 10 are the electrograms obtained from the
sites indicated in Figure 9, with the earliest site
located near the right ventricular outflow tract, as
well as six other selected sites. Of note is the earliest
activation occurring near the minimum voltage gradient produced by the shock itself. The morphology
of the earliest activation also is of the QS type,
Circulation Vol 82, No 1, July 1990
254
1
2
3
4 5
6 7
8
9 10
11
12
14.0Omsec
50
50 mV
DEFIB _S
SDS = 4
1 2
3 4 5 6 7 8 9 1011
12
6 7 8 9 10 11
12
6.5msec
50 mV
2 3 4
1
5
30.5 msec
50 mV
|
U
50 mv
1 2
3
3
2
1
~~~~~~3015 msec
3
4
5
4
5
6 7 8 9 10 11
7
8
9 10 11
12
12
msec
50 mV
-~200 ms
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
1
2
34 5 67 8
9 1011
12
dV/dt
#10, -5.4 V/sec
#11, -6.3 V/sec'
msec
~~~~~~~~~75.5
#12, -13.9 vsec
mso
DEFIB
FI E 840
FIGURE 8. Successful defibrillation -total ventricullar fibrillation (VF) termination type. Electrogram recordings from sites
designated in Figure 7 as the earliest (*) and six other selected sites. All unipolar electrogram recordings are shown with their
algorithm-chosen 11 preshock activations and a first postshock activation designated the 12th activation. Relative activation times
are listed adjacent to the first postshock activation numbered 12 on all waveforms and correspond to the values depicted at the
button sites in Figure 7, lower paneL The standard deviation separation (SDS) values are as shown for the three recording sites on
the button containing the earliest recorded activation. An expanded view of the dV/dt for this earliest site demonstrates the clear
distinction of underlying activation during either VF or after successful shock from the actual defibrillation shock itself. Values for
dV/dtfor the last two activations before shock and thefirst postshock activation are given for this electrogram. The saturating signal
associated with defibrillation has been clipped under software control in all plots for clarity of presentation. Time and amplitude
scales as shown.
activity could be found. These were most commonly
consistent with the finding that this site is the origin
for this activation wavefront. The open arrow in
clustered at defibrillation voltage levels near the
Figure 10 indicates the occurrence of saturation of
defibrillation threshold. In contrast to unsuccessful
the + 130-mV amplifier due to a signal presented by
defibrillation, however, the number of topologically
the myocardium or electrode after the defibrillation
distinct sites was never greater than one. If two
shock has terminated. This postshock overshoot was
geographically disparate sites demonstrated residual
not observed in recordings performed near the
fibrillation after shock, then the shock was never
cathodal patch. Such overshoots and their resultant
found to be successful. All cases of this type of
amplifier saturation were never observed to last for
defibrillation with a single residual focus of
successful
more than 10 msec with the defibrillation patch
fibrillating activity terminated within one to three
configuration and the amplifier range employed, and
activations. Of the 23 successful defibrillation
their appearance could easily be differentiated from
attempts of this incomplete VF termination type, 10
underlying activation as shown in Figure 10. For
unsuccessful defibrillation, the average minimal voltof 23 (43%) terminated within one activation, 12 of
age gradient value found in the six animals studied
23 (52%) terminated within two activations, and one
was 6.5 + 1.8 V/cm (mean+ SD), with the largest value
of 23 (4%) required three activations before termibeing 8.5 V/cm. In other words, no defibrillation
nation. The single site of residual fibrillating activity
attempt that produced a minimal epicardial value in
was
always located at, or one button site away from,
excess of 8.5 V/cm was unsuccessful.
the minimum voltage gradient produced by the
Successful Defibrillation With Incomplete Ventricular
shock. An example of this form of successful defibrilFibrillation Termination
lation is given in Figures 11 and 12 for a 5-J shock.
A second pattern of successful defibrillation with
In 23 of the 139 defibrillation attempts (17%) that
an initial residual area of fibrillating activity was
were successful, a single site of residual fibrillating
200
Witkowski et al Mechanisms of Cardiac Defibrillation
255
110889, Episode 13a, 310 V/1O msec
RV
VOLTAGE GRADIENT MAP
/8.6
Mean Global Voltage Gradient = 12.9 ± 6.3 V/cm
Minimum Voltage Gradient = 4.2 V/cm
Maximum Voltage Gradient = 30.6 V/cm
Ratio of Max/Min = 7.3
s 4
*424
*6.9
/
*6.1
80
LV
7.7
6.6
*4.5
*7.4
8.8
083
*.
i,.v°"
"
O.
,
*12.O
-121
\,,,.#..,
*6.017.1
""
i.g
-1
1.11.1
J
.9
19.7
*15.1
*
Left antero-lateral view
1st POST-SHOCK ACTIVATION MAP
(and accompanying SDS VALUES)
A-
RV -
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
Total Epicardial Activation Time = 93.5 msec
Mean Global SDS value 7.7 + 5.9
Minimum Button SDS value =1
Right postero-lateral view
=
LL46.fJ
22.5Am,.
0
33.CGM
24.5J
*25
480
.~~~v'/~~48.5
*47.O~~~~1'
/
~48
2
545°3'9
346.0105
57.0n3
1
LV
0'O...,,, 20' '0".L
~
*21.0n*250j,.'
FD'
~
.9il
M
35j.J46.J
L
.57251C50
.5E..
*
2.0 12
395
RV
i *
7.0n
E~~~~
Left antero-lateral view
Right postero-lateral view
FIGURE 9. Representative voltage gradient map andfirstpostshock activation mapfor an unsuccessful defibrillation attempt near
threshold in dog 10889. (Format similar to Figure 7.) Minimum button standard deviation separation (SDS) value of 1 documents
that at least one site has been left fibrillating. This site is located near the right ventricular outflow tract, at the minimum of the
voltage gradient, and is also the site of earliest postshock activation as indicated by the asterisk. Six additional sites are noted by
curved arrows and labeled A-F in the lower panel. (See Figure 10 for the electrograms found at the earliest site and the six
additional sites.)
rarely observed (three episodes in one dog) that
slightly differed from the first in that it was seen at
slightly lower leading-edge voltage levels, usually less
than 300 V, and was characterized by a second
activation wavefront present at approximately the
same time as the wavefront initiated by the residually
fibrillating myocardium. However, this second focus
was initiated in an area in which VF was terminated
as judged by the SDS value of more than 2. This
second focus was located between the area of residual VF and the rest of the heart. It appeared that this
second focus launched a wavefront both toward the
remaining ventricular myocardium and toward the
residual fibrillating tissue. The collision of these two
activation wavefronts appeared to effectively surround the residual fibrillating tissue with a refractory
envelope, and subsequently the fibrillation ceased
within two or three beats, which is the same mode of
extinction seen when this second activation front was
not observed. The occurrence of this second wavefront was spontaneous, and there is no way to judge
if the defibrillation attempt would have also been
successful if this second wavefront was not present.
No attempt was made to simulate the occurrence of
this second potentially encapsulating waveform with
an appropriately timed pacing stimulus. Just as in the
first form of successful defibrillation with a single site
left fibrillating, the site that was clearly a continuation of previous fibrillating activity in this second
form was limited in our observations to a single site,
and that site was located near the minimum voltage
gradient. The average minimal voltage gradient produced during all forms of successful defibrillation for
the six animals studied was 4.0±1.1 V/cm with a
smallest value of 2.9 V/cm. In other words, no
defibrillation shock producing a minimal voltage gradient of less than 2.9 V/cm was successful. When
combined with the data found for unsuccessful
defibrillation, a minimal voltage gradient between 2.9
and 8.5 V/cm could result in either a success or a
failure to defibrillate.
Discussion
Higher-energy defibrillation causes more myocardial damage19; more rapidly depletes the batteries in
an implanted device, necessitating more frequent
generator changes; and requires larger generators.
Even if a major technological breakthrough in capacitor or battery design is made to significantly reduce
the device size, it would still be desirable to reduce
the myocardial damage associated with higher-
Circulation Vol 82 No 1, July 1990
256
1
100
A
2 3
4
5 6 7 8 9 10 11 12
jI
,
4 56 7 8 91011
1 2 3
100
m
12
b
/19.5
j1
*
2
15.5 msec
1
2 3 4 5 6 7 8 910 11
m sec
12
100 mV
/D//
2 3 4 5 6 7 8 9 10 11
1
*
3
p33.5
mV
12
0.0
1
2
3
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
10mV/
4
5
/
6
7
8
9 10 11
msec
msec
12
77.0Omsec
100 mV
F!
e DEFIB
FIGURE 10. Electrogram recordings during an unsuccessful defibrillation attempt from the sites designated in Figure 9 as the
earliest (*) and the six other selected sites. (Format similar to Figure 8.) Note the standard deviation separation (SDS) values at
the three electrodes forming the button with the earliest recorded activation all indicate that their respective first postshock
activations are a continuation of the preshockfibrillating activity. An expanded view of the earliest of these three sites clearly shows
the points chosen for activation in the derivative of the waveform (dV/dt). The open arrow on the expanded dV/dt waveform points
to the occurrence of transient amplifier saturation for less than 5 msec that occurred after the shock and is easily differentiated from
true activation when both the V(t) and dV/dt wavefonns are examined.
40msec
energy defibrillation and to eliminate the need for a
thoracotomy for patch placement.
The in vivo measurement of the myocardial voltage
gradient produced by a defibrillation shock has been
previously documented to be important in determining the response of the fibrillating myocardium. For
defibrillation shocks at levels just below defibrillation
threshold, the first site of initial postshock activation
from which fibrillation resumed has previously been
shown to be at a site of minimum potential
gradient.18 Similarly, for successful defibrillation
attempts where the initial postshock activation
occurs relatively early, this first activation was found
to originate from an area where the voltage gradient
was weakest.8 Our findings agree with these previously published reports. One significant advantage of
the technique presented for epicardial voltage gradient determination in this study is that the same
conclusions were obtained by a technique that
requires only an epicardial sock to be slipped over
the heart and therefore has the potential to be
applied in the human operating room at the time of
automatic implantable cardioverter-defibrillator
patch placement, similar to mapping techniques com-
200
msec
monly used for the surgical therapy of malignant
ventricular arrhythmias. Our preliminary studies of
applying the defibrillation shock synchronized to the
QRS complex in sinus rhythm have produced identical voltage gradient fields compared with the same
shock delivered in ventricular fibrillation in normal
dog hearts as might be expected. Actual button
electrode locations would only need to be approximated intraoperatively, as is currently done for
online surgical mapping. This would allow a minimal
energy defibrillation shock to be applied synchronized with the QRS complex in sinus rhythm and the
fields mapped, avoiding the need for multiple
defibrillation tests in patients with extremely poor
left ventricular function or in whom the arterial
pressure returns to baseline only slowly after a fibrillation and subsequent defibrillation episode. The
patch placement could then be optimized for the
quantifiable parameter of field homogeneity before
performing defibrillation threshold determinations.
The extrapolation of the results presented in normal
dog hearts to patients requiring an implantable
defibrillator must be made with caution, however,
because fibrillatory rates differ and geometrical alter-
Witkowski et al Mechanisms of Cardiac Defibrillation
257
#10689, Episode 25, 320 V/10 msec
VOLTAGE GRADIENT MAP
RV
LV
Mean Global Voltage Gradient = 14.8 ± 7.6 V/cm
Minimum Voltage Gradient = 5.1 V/cm
Maximum Voltage Gradient = 35.0 V/cm
Ratio of Max/Min = 6.8
RV
.2
,
13.1
*25.6
0
20.2
21.9,1
13.5
0f
X
29
26.5
*,29.8
6.0
*15.2
*<1350
*
/
~~~~~~~~~~~~~~~22.1
Rg t..
_............postero
Right postero-laterali view
1st POST-SHOCK ACTIVATION MAP RV
}
(and accompanying SDS VALUES)
Downloaded from http://circ.ahajournals.org/ by guest on October 2, 2016
Total Epicardial Activation Time = 105.0 msec
Mean Global SDS Value = 9.2 ± 6.2
Minimum Button SDS value = 1
C
Left antero-lateral
view
Right postero-lateral
view
FIGURE 11. Representative voltage gradient and first postshock activation maps for a successful defibrillation trial (incomplete
ventricular fibrillation termination type) that initially had a site of residual fibrillating activity in dog 10689. (Format similar to
Figure 7.) Note the minimum button standard deviation separation (SDS) value of 1 similar to unsuccessful defibrillation as shown
in Figure 9 again located near the right ventricular outflow tract near the minimum voltage gradient produced by the defibrillation
shock. The site of earliest postshock activation is indicated by an asterisk (*) and six other selected sites are designated by curved
arrows and labeled A-F. (See Figure 12 for the electrograms recorded at these sites.)
ations engendered by fibrosis, aneurysms, and so on
significantly affect the voltage gradient distributions and the response of the fibrillating myocardial
tissue. In our study, the highest epicardial voltage
gradient minimum found for an unsuccessful defibrillation attempt was 8.5 V/cm. Therefore, if a shock
produced a minimal value of 8.6 V/cm, it was always
found on retrospective analysis of the data to have
been successful by one of the two mechanisms that
we have described. Obviously, this would also need to
be prospectively tested. Other defibrillation patch
configurations that do not as uniformly defibrillate
the interventricular septum may also require septal
recording sites. Whether such a demarcation point
also applies to hearts with chronic scars, dilated
cardiomyopathies, or aneurysms remains to be investigated.
A major finding of this study is that the progression
from significantly subthreshold defibrillation shocks
to shocks that completely terminate fibrillation with a
nearly 100% success rate is a continuous one. For
markedly subthreshold defibrillation shocks, multiple
areas are left fibrillating, and VF resumes initiated
from multiple sites. As one approaches the defibrillation threshold, greater volumes of fibrillating tissue
are terminated with resultant smaller areas left fibmay
rillating, and the locations of these residual areas lie
in regions in which the voltage gradient field produced by the shock is lowest. Near threshold, if a
single site is left fibrillating, it can either go on to
reinitiate global VF or not, depending on factors that
appear to be randomly distributed, and may be
related to the geometry of the prior activation loops,
fiber orientation, loading effects presented by the
adjacent nonfibrillating ventricular muscle, and
shock field direction. Of these four, the activation
loop and loading effects are variable. The result of
this heterogeneity of response at shock levels near
threshold is that for identical voltage and current
shocks in the same animal that produce identical
voltage gradient fields, we have observed each of the
three possible scenarios, namely, unsuccessful
defibrillation, successful defibrillation of the complete termination type, or successful defibrillation of
the partial VF termination type. The voltage gradient
range over which this overlap occurs is most probably
the basis for the well-documented "probability of
defibrillation curve" rather than a discreet demarcation between success and failure to defibrillate. For
clinical applications, techniques to ensure an operating point well within the total VF termination window would obviously be desirable.
258
Circulation Vol 82, No 1, July 1990
1 2 3 4 5
100 mV
*
AI1
6 78
9 1011 12
2.0 msec
100 mV
Al
B
*
2
C
*
3
1
D
2 3 4
5 6
7 8 9 1011
12
mV
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E
F
40msec
DEFiB -0
FIGURE 12. Electrograms recorded during an episode ofsuccessful defibrillation (incomplete ventricular fibrillation termination
type) that demonstrated a site of residual but transient fibrillating activity. Sites labeled as earliest (*) and A-F refer to locations
indicated in Figure 11. (Fortnat identical to Figure 10.) In this case, residual fibrillating activity extinguished after a single
propagated wavefront was initiated.
200
Our conclusions are based on a direct analysis
approach to the question of whether the first postshock activation is a continuation of the preshock
fibrillating activity. In all unsuccessful defibrillation
attempts examined in the present study using continuous DC-coupled recording techniques, at least one
site was clearly found that was judged to be a
continuation of the previous fibrillating activity at
that site. Similarly, in no case did we find VF to be
uniformly terminated and then fibrillation to be
regenerated de novo. We have made every effort to
verify that our algorithms for choosing activations
during VF are statistically valid and that our mapping
tools are free from unknown artifacts. Our conclusion that for unsuccessful shocks near threshold the
earliest site represents a continuation of preceding
VF is just the opposite of the conclusion drawn by
Ideker's group (Chen et a18 and Shibata et al10). They
used an indirect analysis technique examining the
time from the shock to the first postshock activation
and concluded that unsuccessful shocks near threshold halt all activation fronts, after which VF regenerates. Their findings are based on the finding of an
"isoelectric window" of variable duration after such
an unsuccessful defibrillation attempt.810 They did
not incorporate the inherent variability that is present in activation sequences from any given site and
me
from one VF episode to the next, nor the timing of
the first postshock activation from the last preshock
activation into their analysis. This previous study
concluded that such unsuccessful shocks near threshold halt all activation fronts after which fibrillation is
regenerated anew, but that for lower energy unsuccessful shocks the underlying fibrillation was not
affected and simply continued in regions of lowest
shock voltage gradient. Indeed, their first postshock
activation for a subthreshold unsuccessful defibrillation attempt (Figure 4C, approximately channel 19)8
conveys the same information as our Figure 10.
There are several differences between their study
and our study, including the use of polarizable electrodes, blanking intervals of approximately 15-20
msec longer than ours, use of bipolar recording
electrodes that are wavefront direction dependent,
the use of AC-coupled rather than DC-coupled electrogram recording techniques, and switched rather
than continuously connected amplifier arrays. However, none of these differences are sufficient to
explain the different conclusions. The different conclusions are based on the definition used to classify
what is a continuation of VF.
At near defibrillation threshold shock levels, the
vast majority of the ventricular myocardium has been
effectively defibrillated, and indeed all fibrillating
Witkowski et al Mechanisms of Cardiac Defibrillation
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activity in those areas so affected ceases. This is true
whether the defibrillation is successful or unsuccessful, and the coordinated appearance of the first
postshock activation in Figures 9 and 11 attest to this
fact. The remainder of the heart in these cases
appears to behave as a simple excitable syncytium,
but its loading effect may play an important role in
whether a single residual fibrillating site goes on to
rekindle global fibrillation or whether it selfextinguishes. Recent studies have emphasized the
importance of the interactions between the kinetics
of depolarizing currents (presumably sodium current) and the passive anisotropic properties in regulating the safety factor of propagating impulses.20
The kinetics of the ionic channels are markedly
influenced from site to site by electrical load differences dictated by the downstream membrane capacitance to be discharged due to anisotropic structural
complexities.21 These previous elegant studies used
paced in vitro preparations, but presumably similar
arguments may apply to the conditions required to
sustain initially localized VF in situ.
The finding of the type of defibrillation where all
fibrillating activity ceases is not a new finding. It was
clearly described in 1974 by Mower et a122 and
termed pattern 1; it was subsequently renamed type
A recovery by Chen et al.8 Similarly, the type B
successful defibrillation recovery that has been previously described8 corresponds to successful defibrillation with incomplete termination of all fibrillating
activity. Our findings have described similar phenomena but provide a different insight into the underlying
mechanisms responsible for these findings. The exact
mechanism of ventricular fibrillation is unknown;
however, the majority of evidence points to a reentrant etiology for this disturbance. If there are multiple reentrant loops or vortexes that are continuously migrating in the myocardium during fibrillation,
then a possible explanation for defibrillation is the
temporary electrical snipping of segments of these
loops by either activation of partially refractory tissue
and subsequent loop termination or by prolongation
of the repolarization phase of tissue found to be in
phase 2 or 3. Such action potential prolongation by
defibrillation level shocks has been observed in vitro
by intracellular recordings,23 in myocardial cell
aggregates by extrastimulus techniques,24 and in isolated rabbit hearts by voltage-sensitive dye
techniques,25 with all of these studies performed
during a paced regular rhythm. Similar recordings
have not yet been reported, to our knowledge, in vivo
during a defibrillation attempt. It is interesting to
speculate that the organized low-level biphasic waveform observed in Figure 8 immediately after the
shock in the three earliest sites is the extracellular
manifestation of repolarization homogenization
resultant from the successful defibrillation shock.
Confirmation of the etiology of this biphasic waveform awaits simultaneous extracellular and intracellular recordings in vivo. If this is indeed a primary
mechanism of defibrillation, it is purely speculative at
259
this point as to which of the several known membrane
currents involved in the regulation of the action
potential plateau would be involved, including the
L-type Ca2' current,26 the Na+ "window" or slowly
inactivating current,27 and the K' currents.28 Insight
gained into the responsible ionic mechanism may
translate into more efficient means of achieving the
desired goal.
In summary, a technique was devised for measuring the epicardial voltage gradient field produced by
a defibrillation shock that could be used for a similar
application in a clinical setting. With this technique,
the critical mass hypothesis for defibrillation was
verified to be applicable to one type of successful
defibrillation with the required amount of myocardium affected definitely less than 100%. For the
second distinct form of effective defibrillation, the
total extinction hypothesis appears correct. Finally,
unsuccessful defibrillation is adequately explained by
the failure to defibrillate at least one region of
myocardium, and no additional vulnerability arguments need to be invoked to explain unsuccessful
defibrillation.
Acknowledgments
The authors wish to thank Medtronic for their
contribution of defibrillation patch electrodes and
the 2394 External Cardioverter/Defibrillator, Ms.
Shelly Schilbe for preparation of the manuscript, and
Ms. Katherine Jones for her technical assistance with
the experiments and the data analysis.
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KEY WoRDs * unipolar electrograms * cardiac electrophysiology
* automatic implantable cardioverter-defibrillator * ventricular
fibrillation
Mechanism of cardiac defibrillation in open-chest dogs with unipolar DC-coupled
simultaneous activation and shock potential recordings.
F X Witkowski, P A Penkoske and R Plonsey
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Circulation. 1990;82:244-260
doi: 10.1161/01.CIR.82.1.244
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