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Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Transmembrane potential change
(
Vm) during
shocks was recorded by a double-barrel microelectrode in 12 isolated
guinea pig papillary muscles. After 10 S1 stimuli, square-wave S2
shocks of both polarities were given consisting of 10-ms monophasic and 10/10-ms and 5/5-ms biphasic waveforms that created potential gradients
from 1.1 ± 0.3 to 11.9 ± 0.4 V/cm. S2 shocks were applied with
30, 60- to 70-, and 90- to 130-ms S1-S2 coupling intervals so that they
occurred during the plateau, late portion of the plateau, and
phase 3 of the action potential,
respectively. Some shocks were given across as well as along the fiber
orientation. The shocks caused hyperpolarization with one polarity and
depolarization with the opposite polarity. The ratio of the magnitude
of hyperpolarization to that of depolarization at the three S1-S2
coupling intervals was 1.5 ± 0.3, 1.1 ± 0.2, and 0.5 ± 0.2, respectively.
Vm during the
shock was significantly greater for the monophasic than for the two
biphasic shocks. The prolongation of total repolarizing time (TRT) was
significantly greater for monophasic (119.8 ± 19.1%) and 10/10-ms
biphasic (120.5 ± 18.2%) than for 5/5-ms biphasic (113.0 ± 12.9%) waveforms. The dispersion of the normalized TRT between
instances of hyperpolarization and depolarization caused by the two
shock polarities was 7.4 ± 7.1% for monophasic, 3.0 ± 4.1%
for 10/10-ms biphasic, and 2.8 ± 3.1% for 5/5-ms biphasic shocks
(P < 0.05 for monophasic vs.
biphasic). Shock fields along fibers produced a larger
Vm and
prolongation of TRT than those across fibers. We conclude that
1) a change in shock polarity causes
an asymmetrical change in membrane polarization depending on shock
timing; 2) the 5/5-ms biphasic
waveform causes the smallest Vm, prolongs
repolarization the least, and causes the smallest polarity-dependent
dispersion; and 3) the changes in
transmembrane potential and repolarization are influenced by fiber orientation.
depolarization; hyperpolarization ; action potential duration; defibrillation
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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THE RESPONSE of myocardial
cells to an electrical shock occurs in several steps. The initial step
is a change in the transmembrane potential
(Vm) caused
by the shock. This change includes depolarization and/or
hyperpolarization depending on local shock strength, shock polarity,
and fiber orientation (2, 4, 14, 29). Because many ionic channels in
the cell membrane are voltage dependent, the
Vm caused by
the shock affects the activation state of voltage-dependent channels.
These channels in turn affect excitability, action potential duration,
and the refractory period following the shock. Many studies of
defibrillation mechanisms have investigated the changes in action
potential duration, refractory period, and excitability of myocardium
after a shock (2, 19-22, 32),
Recently, studies have reported the
Vm caused by a
shock (4, 7, 13, 14, 29, 31). Optical recording techniques have been
used to study
Vm during a
shock in single isolated myocardial cells (13), in a layer of
myocardial cells (7), and in isolated perfused rabbit hearts (1, 2, 4,
14, 29). Because
Vm during the
shock recorded in isolated hearts by optical techniques represents the
averaged potential changes from many cells (2, 29), a double-barrel
microelectrode that can record from a single cell and can minimize the
shock artifact has also been used to record the transmembrane potential
during a shock (31). Both optical and microelectrode recording
techniques have found that hyperpolarization is greater than
depolarization when a shock is delivered during the action potential
plateau (4, 7, 13, 29, 31). A recent report shows that the magnitude of
hyperpolarization and depolarization is not significantly different
when the shock is given during the later portion of the plateau (7). It
still is not clear how the transmembrane potential changes when the
shock is delivered during phase 3, a
portion of the action potential thought to be crucial for
defibrillation and for the electrical induction of fibrillation.
Another approach to study the
Vm caused by a
shock is the use of mathematical models to predict the relation between
the shock strength and the response of the transmembrane potential, but
some of the results of these models are conflicting (17, 23). Recently,
computer models have also been used to explain the reasons for
unsuccessful defibrillation (10, 11, 16) and to predict better
monophasic and biphasic waveforms for defibrillation (25). More
experimental data are required to test the predictions of the
mathematical models and to establish the values of certain parameters
used in these models.
Since early basic research by Jones et al. (8, 9) showed beneficial
effects of biphasic waveforms for defibrillation, some biphasic
waveforms have been demonstrated to be more efficient than monophasic
waveforms for successful defibrillation (5, 6, 18). Hypotheses for the
higher efficacy of defibrillation of biphasic shocks usually involve
differences in excitation threshold and prolongation of action
potential duration and refractoriness for monophasic and biphasic
waveforms (9, 19, 21, 22, 32). For example, extensive experimental
studies and computer models from Jones et al. (9, 11, 19, 22) have
demonstrated that a biphasic waveform produces greater prolongation of
action potential duration and smaller dispersion of action potential prolongation than a monophasic waveform at low shock intensities, which
they postulated is crucial for a successful defibrillation. Although
the Vm caused
by the shock has been recorded during monophasic shocks (1, 7, 13,
29-31), no experimental data have been reported to show
Vm recordings
during biphasic shocks. Investigation of
Vm caused by
shocks should furnish more experimental data for computer models (10,
11, 16, 25) and help elucidate the basic mechanisms of defibrillation.
The main purpose of this study was to determine the
Vm caused by
monophasic and biphasic field stimulation during different phases of
the action potential by using double-barrel microelectrode recordings
in guinea pig papillary muscles. Because a minimum shock potential
gradient of 4-6 V/cm is thought to be necessary for defibrillation
(28), potential gradients lower than, equal to, and greater than this
were examined, with an emphasis on the lower potential gradients.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Tissue preparation.
Twelve guinea pig papillary muscles were used. Guinea pigs weighing
~300 g were injected with Nembutal (75 mg in 1.5 ml saline) via the
abdomen. The hearts were rapidly excised through a median sternotomy
and immersed in cold Tyrode solution. The Tyrode solution had the
following formula (mM): 129 NaCl, 1.8 CaCl2, 1.1 MgCl2, 4.5 KCl, 1 Na2HPO4,
20 NaHCO3, and 11 glucose. The
left ventricular anterior papillary muscle, ~4-mm long, was removed
and pinned on silicon rubber in the center of a 2 × 2-cm tissue
bath. The tissue was then continuously superfused with Tyrode solution
bubbled with a 95% O2-5%
CO2 mixture, giving a pH range of
7.35-7.40. Solution temperature was maintained in the range of
35-36°C. The cardiac tissue was paced at one end via two
extracellular 0.1-mm-diameter electrodes with a stimulator controlled
by a Macintosh II computer. In seven guinea pig papillary muscles, two
mesh platinum shock electrodes (16 × 10 mm) were placed on
opposite sides of the tissue bath and immersed in the Tyrode solution
to generate an electric field through the tissue bath that was along
the longitudinal direction of the tissue. In this way, the fiber
orientation of the papillary muscle was parallel to the electrical
field vector. In another five guinea pig papillary muscles, a mesh
platinum shock electrode (10 × 6 mm) was placed on each of the
four sides of the tissue bath so that the electrical field vector could
be generated either parallel or perpendicular to the longitudinal direction of the tissue, depending on which electrode pair was used. In
this way, the influence of the fiber orientation on the Vm during a
shock could be studied.
Signal recordings.
The technique of recording the signals has been published previously
(31). To make a double-barrel microelectrode, two single glass
capillaries (Glass 1BBL W/FIL 1.0 mm, WPI, Sarasota, FL) were glued
together except in the region where the tips were to be formed and were
pulled by a horizontal micropipette puller (Industrial Science
Associates, Ridgewood, NY). The capillary tubes were pulled to have an
impedance of ~10 M
for each tip when filled with 3 M KCl. The
distance between the microelectrode tips measured under the light
microscope varied from several micrometers to several tens of
micrometers. Only those double-barrel microelectrodes with a 15- to
50-µm distance between the two tips were used. Each double-barrel
microelectrode was mounted on a motorized micromanipulator (DC3001,
WPI). Each barrel of the double-barrel microelectrode was connected to
the input of a differential preamplifier (Duo 773 Dual Microprobe
System, WPI) with an Ag-AgCl wire. Capacitor compensation within the
preamplifier was used to eliminate capacitive coupling between the two
tips. The signals were recorded differentially as a voltage between the
two double-barrel microelectrode tips. After preamplification, the
signal was recorded with direct-current coupling using a data
acquisition system. Signals were recorded digitally with 12-bit
accuracy at a rate of 8,000 samples/s. The data were stored on optical
disks for later computer analysis.
Experimental protocols. The double-barrel microelectrode was slowly lowered into the Tyrode solution just above the tissue with a motorized micromanipulator. It was then rotated until the potential difference was almost undetectable on the monitoring oscilloscope during shocks that created a shock field of ~10 V/cm. The double-barrel microelectrode was then lowered into the tissue until an action potential was seen in the differential recording between the two barrels shown on a monitoring oscilloscope. The location of the recording site was ~1 mm away from one end of the papillary muscle. After 10 S1 stimuli at twice diastolic threshold were given through the pacing wires with a 300-ms S1-S1 interval, an S2 shock was given through the shock electrodes to produce different levels of potential gradient in the papillary muscle at the double-barrel microelectrode. Each S2 shock was a symmetrical square wave consisting of a 10-ms monophasic, 10/10-ms biphasic, or 5/5-ms biphasic waveform. The shape of the shock waveform was programmed by a Macintosh II computer. The computer program sent the waveform information to a current-source arbitrary waveform generator that was connected to the shock electrodes and created the required waveform across the tissue bath.
In seven papillary muscles, three shock strengths created potential gradients of ~3, 6, and 12 V/cm. Each shock level with the same S1-S2 coupling interval was given twice, the second time with the electrode polarity reversed. The S2 shock was given with three S1-S2 coupling intervals, i.e., 30, 60-70, and 90-110 ms, so that the S2 shocks were delivered during the plateau, the late portion of the plateau, and phase 3 of the 10th S1-induced action potential, respectively. When the S2 shock was delivered during the action potential plateau with a 30-ms S1-S2 coupling interval, all three levels of shock potential gradients were given. When the S2 shock was delivered with longer S1-S2 coupling intervals, i.e., 60-70 and 90-110 ms, only a medium level of shock potential gradient (~6 V/cm) was used. The order of S2 testing of each waveform, polarity, and S1-S2 coupling interval was determined randomly. All recordings were made from the same impalement for each papillary muscle. In another five papillary muscles, shocks creating five levels of potential gradients ranging from 1.1 ± 0.3 to 4.3 ± 0.5 V/cm were given during phase 3 of the action potential with a 90- to 130-ms S1-S2 coupling interval. Each shock level was given twice, the second time with the reversed shock polarity. After the shocks for one electrode pair were given, shocks with the same strength, polarity, and S1-S2 coupling interval were given from the other electrode pair during the same impalement. The order in which shocks were given along or across fibers was randomly chosen. At the end of the study, the double-barrel microelectrode was withdrawn into Tyrode solution to recheck whether there was a shock artifact and to obtain an extracellular potential.Data analysis.
The control transmembrane action potential was defined as the ninth
S1-induced transmembrane action potential during which no shock was
delivered (Fig. 1). The test transmembrane
action potential was defined as the 10th S1-induced action potential during which an S2 shock was delivered (Fig. 1). Depolarization of the
membrane potential during a shock was defined as a more positive
membrane potential during the shock than just before the shock (solid
tracings in Fig. 1), whereas hyperpolarization was defined as a more
negative membrane potential during the shock than just before the shock
(dotted tracings in Fig. 1). This definition was true when a monophasic
shock waveform was used (top tracing in Fig. 1). A biphasic shock
caused a biphasic change in the
Vm (lower 2 tracings in Fig. 1). The polarity of a biphasic waveform was
arbitrarily considered to be the polarity of its first phase so that
both monophasic and the first phase of biphasic waveforms would cause
the same direction of
Vm, as shown
in Fig. 1. The shock causing depolarization (solid tracings in Fig. 1)
at the microelectrode recording site was called a depolarizing shock, and the shock causing hyperpolarization (dotted tracings in Fig. 1) was
called a hyperpolarizing shock.
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Vm is the
absolute value of the maximum voltage difference between the membrane
potential just before the shock and that just before the end of the
shock, i.e., the potential difference between arrows
1 and 2 in the top
tracing in Fig. 1. Because a biphasic shock caused biphasic changes in the transmembrane potential,
Vm was
determined both at the end of the first phase (voltage difference
between arrows 1 and
2 in the bottom 2 tracings in Fig. 1)
and at the end of the second phase, which was called the net
Vm (voltage
difference between arrows 1 and
3 in the bottom 2 tracings in Fig. 1).
The difference between the
Vm at the end
of the first phase and the
Vm at the end
of the second phase was also determined and was called the reversal
Vm (voltage
difference between arrows 2 and
3 in the bottom 2 tracings in Fig. 1).
The net Vm and
the reversal
Vm for
biphasic shocks were said to indicate depolarization when the potential
at arrow 3 was greater than at
arrow 2 (dashed tracings in Fig. 1)
and were said to indicate hyperpolarization when the potential at
arrow 3 was less than at
arrow 2 (solid tracings in Fig. 1).
Shock membrane potential was determined as the membrane potential
immediately before the S2 shock, as indicated by arrow 1 in Fig. 1. Spontaneous repolarization was determined
as the amount of repolarization of the 9th control action potential
during the interval (horizontal bars in 9th S1 action potentials in
Fig. 1) when the shock was given during the 10th test action potential. This was assumed to indicate the amount the membrane potential would
have changed during the shock if the shock had not been given.
APA, TRT (or APD90),
Vm, reversal
Vm, net
Vm, and
spontaneous repolarization were measured using a computer program
written with PV-WAVE (Visual Numerics, Boulder, CO). Inputs to the
program were the S2 with respect to the beginning of the file, the
S1-S1 interval, the S1-S2 interval, the shock waveform morphology and duration, and whether the shock was hyperpolarizing or depolarizing. For APA, the maximum amplitude of the upstroke between the S1 and the
S2 was measured with respect to a 10-ms average of the points beginning
15 ms before the last S1. The measurement points in Fig. 1 were
1) the S2 time,
2) the S2 time plus the duration of
a monophasic shock or the first phase of a biphasic shock, and
3) point
2 plus the second phase of a biphasic shock. As stated above, Vm was
the amplitude at point 2 minus the
amplitude at point 1; net
Vm was the
amplitude at point 3 minus the
amplitude at point 1; and reversal
Vm was the
difference between the amplitude at point
2 and the amplitude at point
3. When the shock field was across the
longitudinal axis of the papillary muscle, the shock artifact (a fast
direct-current offset as shown in Fig. 5) was subtracted from the
measured Vm.
TRT was the time interval between
Vmax of the
upstroke depolarization and the point at which the action potential was
repolarized to 90% of its amplitude. To measure spontaneous
repolarization, the amplitude of the ninth S1 response at the time of
the ninth S1 stimulus plus the S1-S2 coupling interval was measured as
was the amplitude at that time plus the duration of the S2 shock.
Spontaneous repolarization was the difference between the second
amplitude and the first. This is the change in amplitude during the
ninth S1 action potential during the equivalent time that the shock was
delivered during the 10th S1.
The shock membrane potential and RP were measured using an interactive
computer program that allowed amplitudes to be measured by moving a
cursor (ACE/gr: Graphics for Exploratory Data Analysis, 1992). The
shock membrane potential was the difference between the amplitude of
the 10th S1 action potential just before the S2 shock and the amplitude
just before the S1 stimulus. To measure RP, the tracing of the signal
with the tip withdrawn was superimposed on the transmembrane potential.
RP was the difference between the amplitude just prior to an S1
stimulus and the superimposed extracellular potential (Fig. 1).
The paired t-test and analysis of
variance (Student-Newman-Keuls test) were used for statistical analysis
of the data. A P value < 0.05 was
considered significant. Values are given as the means ± SD.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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For the control ninth action potential, APA was 130 ± 9 mV,
APD90 was 127 ± 20 ms, and RP
was 
87 ± 5 mV. The spontaneous repolarization
of the ninth S1-induced control action potential during the time
corresponding to the S2 shock interval was 4.8 ± 2.1, 9.1 ± 2.6, and 19.5 ± 6.6 mV at S1-S2 coupling intervals of 30, 60-70, and 90-130 ms, respectively, for 10-ms monophasic and
5/5-ms biphasic shocks and was 10.1 ± 5.1, 19.9 ± 5.5, and 38.1 ± 12.7 mV, respectively, at the above three S1-S2 coupling intervals for 10/10-ms biphasic shocks.
Vm
caused by shocks during action potential plateau.
The three levels of potential gradient generated by the shock at the
tissue were 3.1 ± 0.2, 6.1 ± 0.2, and 11.9 ± 0.3 V/cm, and
all three potential gradients were applied during the action potential
plateau. Figure 2 shows examples of the
Vm caused by shocks all from the same impalement. One shock polarity induced depolarization (Fig. 2, left),
whereas the opposite polarity induced hyperpolarization (Fig. 2,
right). An asymmetrical response,
i.e., hyperpolarization greater than depolarization, existed for the monophasic waveforms and the first phase of the biphasic waveforms at
each of the three levels of potential gradient. As the potential gradient increased,
Vm during the
shock increased monotonically but not linearly. Increasing the
potential gradient from 5.9 to 12.2 V/cm did not double the magnitude
of Vm. For the
same shock strength,
Vm caused by
the monophasic waveform was almost the same as that caused by the first
phase of the 10/10-ms biphasic waveform but greater than that caused by
the first phase of the 5/5-ms biphasic waveform, especially for the
hyperpolarization response. At the reversal of the two phases of a
biphasic shock, hyperpolarization (Fig. 2,
left) and depolarization (Fig. 2,
right) were greater than the
corresponding changes caused by the first phase of the biphasic shock.
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Vm caused by
shocks during the action potential plateau was asymmetrical.
Figure 3 shows
Vm caused by
monophasic and biphasic shocks. The net
Vm was larger
for the monophasic than for the biphasic shocks (Fig.
3A). The reversal
Vm caused by a
10/10-ms biphasic shock with either polarity was greater than the
Vm caused by the monophasic shock or the reversal
Vm of the
5/5-ms biphasic shock at the same potential gradient (Fig.
3B). The depolarization of the
reversal Vm
caused by the 5/5-ms shock was significantly greater than the
depolarization caused by the corresponding monophasic shocks (Fig.
3B). There was no difference in the
magnitude of hyperpolarization of the reversal
Vm caused by
5/5-ms biphasic shocks and the
Vm caused by
10-ms monophasic shocks. Thus, although the reversal
Vm was greater
for biphasic than for monophasic shocks, the net
Vm at the end
of the shock was smaller for biphasic than for monophasic shocks.
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Vm
caused by shocks during different phases of action potential.
The membrane potential just before the shocks of 6.1 ± 0.2 V/cm
strength was +30.0 ± 8.5, +12.3 ± 8.9, and 25.7 ± 9.5 mV for the S1-S2 coupling intervals of 30, 60-70, and
90-110 ms, respectively. For the monophasic and the first phase of
the biphasic waveforms, shocks causing depolarization caused a larger
response as the S1-S2 interval lengthened (solid tracings in Fig.
4). Conversely, for shocks causing
hyperpolarization,
Vm became
smaller as the shock was given later during the action potential
(dotted tracings in Fig. 4). The responses immediately after the shock
were also different for shocks given during different phases of the
action potential. Immediately after shocks given early during the
action potential plateau, repolarization appeared to continue (30-ms S1-S2 in Fig. 4). For shocks given later during the plateau of the
action potential, a local response appeared to occur (70-ms S1-S2 in
Fig. 4) because the membrane potential immediately after the shock was
more positive than that just before the shock, suggesting the
initiation of active processes by the shock even though it was given
during the refractory period. When shocks were given during
phase 3 of the action potential, the
response resembled a premature action potential (110-ms S1-S2 in Fig.
4). This can be seen most clearly for the hyperpolarizing monophasic
shock and the depolarizing biphasic shocks in which the membrane was first partially depolarized at the end of the shock and then initiated a new action potential (110-ms S1-S2 in Fig. 4).
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Vm responses,
but their response changed as the phase of the action potential
changed.
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Action potential prolongation by shock. Action potential prolongation was characterized by the extension of TRT after the shock. For shocks of 6.1 ± 0.2 V/cm, the normalized TRT was not significantly prolonged (P > 0.05) in comparison with the control value (100% for 9th action potential) for any of the three waveforms with a 30-ms S1-S2 coupling interval, e.g., 103 ± 6% for 10 ms monophasic, 103 ± 8% for 10/10-ms biphasic and 102 ± 2% for 5/5-ms biphasic waveform. For S1-S2 coupling intervals of 60-70 ms, the normalized TRT was significantly prolonged (P < 0.05) for all waveforms, e.g., 114 ± 7% for 10-ms monophasic, 117 ± 9% for 10/10-ms biphasic, and 109 ± 5% for 5/5-ms biphasic waveforms. The normalized TRT for 10-ms monophasic and 10/10-ms biphasic waveforms was not significantly different, but both were significantly greater than that for the 5/5-ms biphasic waveform (P < 0.05). The normalized TRT was significantly prolonged for shocks with 90- to 110-ms S1-S2 coupling intervals, e.g., 142 ± 12% for 10-ms monophasic, 141 ± 11% for 10/10-ms biphasic, and 128 ± 9% for 5/5-ms biphasic waveforms. The 5/5-ms biphasic shocks produced less prolongation of TRT than 10-ms monophasic and 10/10-ms biphasic waveforms (P < 0.05). Neither shock polarity significantly prolonged the repolarization time of the action potential more than the other (P = NS), even though a hyperpolarizing shock usually, but not always, caused a longer prolongation than a depolarizing shock.
We determined the difference between the normalized TRT caused by a depolarizing shock and that caused by a hyperpolarizing shock of the same strength but opposite polarity. This difference, called the polarity-dependent dispersion in the TRT, was significantly larger (P < 0.05) for the 10-ms monophasic waveform (7.4 ± 7.1%) than for either the 10/10-ms biphasic waveform (3.0 ± 4.1%) or the 5/5-ms biphasic waveform (2.8 ± 3.1%) for all coupling intervals together. An example of the dependence of repolarization prolongation on the polarity is also shown in Fig. 4. Thus the two shock polarities for biphasic waveforms caused less dispersion of the action potential prolongation than did the monophasic waveform.Effects of low shock strengths and field direction on
Vm.
The membrane potential just before the shocks was 23 ± 9 mV.
The five levels of shock potential gradients were 1.1 ± 0.3, 1.7 ± 0.3, 2.4 ± 0.3, 3.4 ± 0.5, and 4.3 ± 0.5 V/cm for the
shock fields along the fiber orientation and 1.1 ± 0.3, 1.7 ± 0.3, 2.3 ± 0.2, 3.2 ± 0.3, and 4.2 ± 0.4 V/cm for the shock
fields across the fiber orientation. Figure
5 shows the transmembrane potentials during
shocks that were given along and across the longitudinal axis of one
papillary muscle during early phase 3 of the action potential. All recordings were made from the same
impalement with the line of the two microelectrode tips perpendicular
to the longitudinal axis of the papillary muscle. Only recordings for
the lowest, middle, and highest potential gradients are shown in Fig.
5. The response of the transmembrane potential to the shock becomes
larger with the increase in the shock potential gradients, which were either along or across the fiber orientation. However, at
the same level of shock potential gradient the
Vm for shock
fields along the fiber orientation were obviously larger than that for shock fields across the fiber orientation. Because the line of two
double-barrel microelectrode tips was parallel to the shock potential
gradient vector, which was across the fiber orientation, each recording
shows a shock artifact with a fast, clear direct-current offset. The
Vm between the
fast onset and offset of the shock artifact was smaller than the
Vm for shock
fields along the fiber orientation. Figure
6 shows the mean values of the
Vm caused by
the 10-ms monophasic and the first phase of the biphasic shocks with
different strengths along and across the fiber orientation. For all
three waveforms, the
Vm caused by
shocks along the fiber orientation was significantly greater than that
caused by shocks across the fiber orientation. This phenomenon occurred
at all five levels of shock strengths with either depolarizing or
hyperpolarizing shocks.
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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This study confirms previous reports that shocks cause significant
changes in the transmembrane action potentials, including depolarization and hyperpolarization, and cause prolongation but not
shortening of action potential duration (4, 7, 13, 14, 29, 31). This
study also demonstrates that 1)
there is a dynamic and asymmetrical change in the
Vm caused by
shocks delivered during different phases of the action potential,
2) the
Vm and the
prolongation of the repolarization time are greater for shock fields
along than across the fiber orientation, and 3) biphasic shocks cause fewer
alterations in
Vm at the end
of the shock, shorter action potential prolongation, and smaller polarity-dependent dispersion of the prolongation than monophasic shocks of the same or twice the same total shock duration.
Consistent with previous reports (4, 7, 29, 31), this study
demonstrates that the response of the
Vm to an
electrical shock is asymmetrical depending on the shock timing, with an
asymmetrical response of larger hyperpolarization than depolarization
for the same shock strength when the shock is given during the plateau of the action potential. This asymmetrical response disappears when the
shock is given during the late portion of the plateau of the action
potential. The asymmetrical response appears again when the shock is
given during phase 3 of the action
potential but is reversed with depolarization larger than
hyperpolarization. Thus the response of the membrane potential to a
shock is not constant but undergoes a dynamic and asymmetrical change
as the coupling interval of the shock is changed.
The mechanism for the asymmetrical response of the membrane potential to a shock is not understood, but the phenomenon implies that there may be ionic channel activity during the shock, with a higher impedance to current flow in one direction than the other across the cell membrane, and that the membrane impedance to the current flow changes during different phases of the action potential (12, 26). The major reason for the larger depolarization versus hyperpolarization during phase 3 is probably partial opening of inward-current channels that augment depolarization and hence reduce hyperpolarization. This assumption is supported by the fact that the response of the transmembrane potential after a shock resembles either a new action potential or a graded response (Fig. 4) and both responses involve active membrane processes during the shock. It is not known which channel activity contributes to this response and why active processes can occur at a membrane potential at which inward-current channels are thought to be inactivated.
This study first experimentally demonstrates the larger
Vm caused by a
shock field oriented along the fibers than across the fibers at the
same shock strength. The larger
Vm caused by a
shock field along the fiber orientation has at least two effects. First, a larger depolarization during a shock can cause excitation. This supports the observation of a lower excitation threshold with the
fiber orientation parallel to the shock field than perpendicular to the
shock field (15, 24). Second, a larger hyperpolarization during a shock
can cause more sodium channels to recover as proposed by Jones et al.
(10, 11) so that the cell can more easily be excited after the shock.
However, the role of the fiber orientation in the mechanism of the
electrical defibrillation needs more investigation.
This study experimentally demonstrates that the
Vm caused by
biphasic shocks is quite different from that caused by monophasic shocks. The differences in
Vm include
1) a smaller net
Vm for biphasic than for monophasic shocks, indicating that the membrane potential at the end of the shock was closer to the membrane potential just before the shock for biphasic than for monophasic shocks; and
2) a large reversal
Vm for
biphasic shocks. The results of the smaller
Vm for
biphasic waveforms are consistent with the predictions of the theory
and the mathematical models (11, 16, 25). Those models attribute more
efficacious defibrillation for the biphasic waveform to the mechanism
of removing the excess charge by the second phase of a biphasic shock
(11, 16) or of bringing the membrane potential closer to the preshock
membrane potential (25). Because the alteration in the membrane
potential after a biphasic shock is less in comparison with a
monophasic shock, postshock arrhythmias may be less likely to occur,
resulting in a higher defibrillation efficacy for certain biphasic
waveforms as proposed by Jones and Jones (8). A large
Vm at the
reversal of the two phases of a biphasic waveform may help to excite
the myocardial cells and hence to defibrillate (27). This hypothesis is
confirmed in some studies (27) but not in others (5). Thus, on the one
hand, a biphasic shock can cause excitation, whereas on the other hand
it can cause fewer alterations in the membrane potential leading to a
decreased occurrence of postshock arrhythmias.
Sweeney et al. (20) demonstrated that the prolongation of the refractoriness by an electrical shock is related to defibrillation success. Swartz et al. (19) showed prolongation of the action potential by biphasic as well as monophasic shocks. Prolongation has been proposed as one of the mechanisms for ventricular defibrillation. The prolongation of the action potential duration and hence the prolongation of the refractory period are thought to stop the fibrillating wavefronts when these wavefronts meet refractory tissue, leading to successful defibrillation (2, 19, 20, 32). The results of the present study are consistent with previous reports demonstrating that both monophasic and biphasic shocks can prolong TRT. The extent of the prolongation of TRT depends on 1) shock waveform, 2) timing of the shock, 3) shock polarity, and 4) fiber orientation. Consistent with a previous report (32), the prolongation of TRT was less for the biphasic than for the monophasic waveforms at the same shock strength and coupling interval, especially when the total shock duration was the same, such as 10-ms monophasic vs. 5/5-ms biphasic shocks. This finding is not consistent with results reported by Jones et al. (10, 11, 19), who found a larger prolongation of action potential by a biphasic than by a monophasic shock at low shock strength. This inconsistency may be caused by the use of different tissues, different shock durations, and different S1-S2 coupling intervals of the first phase of the biphasic waveform.
This study also shows that the repolarizing time is influenced by shock polarity, causing a polarity-dependent dispersion in action potential prolongation. This polarity-dependent dispersion is larger for monophasic than for biphasic shocks. A hyperpolarizing shock usually causes a larger postshock response than does a depolarizing shock (Fig. 4), especially during the later portion of the action potential. It is not known from the present study why biphasic shocks cause less action potential prolongation and smaller polarity-dependent dispersion in the prolongation. To answer this question may require investigation of the ionic channel activities during a shock.
Consistent with a previous report (15), a shock field along the fiber
orientation causes longer prolongation of the action potential than a
shock field across the fiber orientation. Because the
Vm caused by a
shock is larger for the field along than for the field across the fiber
orientation, it is quite possible that the
Vm is related
to the action potential prolongation after a shock.
The tissue study shows that the 5/5-ms biphasic waveform causes the
smallest Vm at
the end of the shock and prolongs TRT the least compared with the
10/10-ms biphasic and 10-ms monophasic waveforms. If the smaller
Vm and action
potential prolongation were directly related to the higher
defibrillation efficacy of biphasic waveforms, reduction in monophasic
shock strength below its defibrillation threshold could also cause a
smaller Vm and smaller prolongation of action potential duration. Thus the magnitude of the Vm and
the action potential prolongation may not be the only shock-induced
changes related to defibrillation. Another factor related to successful
defibrillation is synchronization of dispersion of repolarization over
the ventricles after a shock (2, 3, 21). Results of this study also
demonstrate that dispersion in the repolarization time between
depolarizing and hyperpolarizing shocks is smaller for biphasic than
for monophasic shocks, indicating that a biphasic shock may cause more
uniform action potential prolongation than a monophasic shock
regardless of polarization.
In conclusion, the dynamic and asymmetrical changes in the
Vm caused by
shocks of different coupling intervals and polarities represent the
intrinsic nature of the membrane response, implying that the myocardial
response during ventricular defibrillation is complex. A shock field
along fibers produces a larger
Vm and prolongation of repolarization than does a shock field across fibers.
The smaller
Vm, the
smaller action potential prolongation, and the smaller
polarity-dependent dispersion in the action potential prolongation
caused by a biphasic shock compared with a monophasic shock may be
related to the higher success rate of ventricular defibrillation for
certain biphasic shocks than for monophasic shocks. More studies are
still required to elucidate the active membrane processes during a
shock pulse to better understand the mechanisms of ventricular
defibrillation and the higher defibrillation efficacy for biphasic
shocks than for monophasic shocks.
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ACKNOWLEDGEMENTS |
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This work was supported in part by National Heart, Lung, and Blood Institute Grant HL-42760.
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FOOTNOTES |
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Address for reprint requests: X. Zhou, B140 Volker Hall, Box 201, Univ. of Alabama at Birmingham, Birmingham, AL 35294-0019.
Received 15 July 1997; accepted in final form 29 July 1998.
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REFERENCES |
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Top
Abstract
Introduction
Methods
Results
Discussion
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