Download Repolarization Phase at Various Sites of the Right Atrium

Repolarization Phase at Various Sites
of the Right Atrium
By Hiroshi Irisowa, M.D., Ishio Ninomiya, M.D., and
Issei Seyama, M.D.
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ABSTRACT
By means of a suction electrode method, the time course of depolarization
and repolarization was observed in the in situ exposed right atrium of dogs. Under normal conditions the end of repolarization at various sites on the atrium
occurred after the QRS spikes, and therefore, the To wave should be inscribed
after and not during the QRS spikes. The concentric spread of activation originating from the S-A node has been confirmed. The region of inital excitation
does not become the initial focus of repolarization. The initial focus of repolarization is different from animal to animal, and this focus cannot be associated with any special cardiac tissue. The process of repolarization occurs
concentrically from an initial focus that is not limited to any specific region of
the atrium.
ADDITIONAL KEY WORDS atrial action potential
monophasic potential
coaxial suction electrode
T a wave
atrial ECG
propagation of atrial excitation
time course of atrial repolarization
anesthetized dogs
• The process of repolarization of the atrial
musculature as represented by the T n wave
in the electrocardiogram (ECG) has rarely
been studied in terms of comparison with the
process of depolarization. This is mainly
because the T a wave is a small and slow
phenomenon. Most modern textbooks of electrocardiography adopt the view that the atrial
repolarization phase is obscured by the QRS
complex, which occurs normally during inscription of the T a wave.1^1 This assumption
originates from the finding that when complete A-V block occurs, the T a wave can be
seen at the earlier position of the QRS. By
using intracavity electrodes"- 10 and esophageal electrodes, 11 the presence of the T a wave
has been detected, but these methods do
not seem to determine accurately the sequence
of the repolarization phase. Furthermore, according to classical analysis, the atrial recovFrom the Department of Physiology, School of
Medicine, Hiroshima University, Hiroshima, Japan.
Supported by research grant from the Japanese
Ministry of Education, Grant HE-06968-04 from the
National Heart Institute, U. S. Department of the
Army through its Far East Research Office and
Abbott Laboratories, North Chicago.
Accepted for publication January 12, 1966.
96
ery process begins prior to the completion
of atrial excitation and a part of the atrial
complex represents the combined effect of
both processes.12 For these reasons we considered it desirable to determine the end of the
recovery phase more precisely by measuring
the monophasic potential and comparing it
with the conventional ECG.
The Ta wave is a deflection that has a
direction opposite to that of the P wave.
The current explanation of this is that the
wave of atrial repolarization normally follows
the same course as the wave of depolarization.
Since the electrical charges in repolarization
are oppositely arranged across the boundary
between the resting and active tissue, the
resultant potential has a polarity opposite that
seen during depolarization.18 Here again direct experimental evidence to support this
theory is lacking, although it has been suggested indirectly that the spatial atrial gradient14 is approximately zero. If the monophasic potential at various sites of the atrium
could be compared in the in situ atrium,
such finding should provide some experimental proof on the manner in which the recovery wave spreads in the atrium.
Qrcnttrion Research, VoL XTX, Julj 1966
97
ATRIAL REPOLARIZATION
This paper describes experiments
signed to study these two questions.
de-
Methods
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Eight mongrel dogs weighing from 6 to 10
kg were used in these experiments. After the
dogs were anesthetized with sodium pentobarbital (Nembutal, 25 mg/kg), they were intubated
and given artificial respiration by intermittent
positive pressure from a Harvard respiratory
pump. Additional doses of sodium pentobarbital,
5 mg/kg, were administered whenever the
standard ECG was obscured by the electromyogram. The thorax was opened by a trans-sternal
approach at the third intercostal space and the
heart was cradled in the pericardium to make
the right atrium accessible. Warm physiological
saline solution was applied to the epicardium
throughout the experiment.
Monophasic arrial action potentials were recorded with a coaxial suction electrode, made by
passing 0.1 mm silver wire through a polyethylene rube (Intramedic polyethylene tubing, PE
100, I. D. 0.034 and O. D. 0.060 inches). Varnish
(insl-X E-33, INSL-X Products Corp., Yonkers,
New York) was applied to insulate the silver
wire that was long enough to project 0.1 mm
beyond the end of the polyethylene tube (fig. 1A).
The polyethylene tube was approximately 15 cm
long to provide the desired flexibility. Constant
negative pressure applied to the interior of this
tube by a hydro-aspirator attached the tip of the
electrode firmly to the vigorously moving atrial
surface. For the indifferent electrode a silver
band was fitted external to the polyethylene
tube at its tip.
Potential from the coaxial suction electrode
was recorded through a differential d-c amplifier
and by means of a four-channel cathode ray
V.CI
Iron
FIGURE 1
Method of obtaining monophasic action potentials from the in situ heart. A: Diagram of the
coaxial suction electrode employed in the open chest experiment. Longitudinal and crosssectional views are illustrated. B: Coaxial suction electrode used in the closed chest experiment.
Outer polyethylene tube was led outside the body through the posterior thoracic waU. PE, polyethylene tube; SW, silver wire; V, varnish; SB, silver band; IPE, inner polyethylene tube;
OPE, outer polyethylene tube; F, flange for fixation; SUC, negative pressure. C: Top is lead
II ECG. A part of the QRS spike has been retouched. Et and Et are monophasic action
potentials taken simultaneously from two different sites of the right atrium shown in the
diagram. Lower dots represent time interval of 68 msec. For explanation see text.
GrcuUtion Rejearch, Vol. XIX, July 1966
IRISAWA, NINOMIYA, SEYAMA
98
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oscilloscope (Nihon Koden model VC 7). Shortly after injury, the monophasic potential was
established and after about two to five minutes
the action potential pattern assumed a steady
form. Using matched suction electrodes with almost the same dimensions and calibrations, depolarization and repolarization were both recorded continuously from two sites on the atrium
and then compared (fig. 1C, E t and E 2 ). Lead
II ECG was recorded simultaneously, so that its
QRS spikes could be used for time reference.
Duration of action potential was measured from
the onset of monophasic potential (fig. 1C, l 0
and 2,,) to the completion of repolarization phase
( l e and 2 e ). Because of the apparent difficulty involved in defining the time of completion of
monophasic action potential, the repolarization
slope was extrapolated arbitrarily to the base line
and the intercept was used as the time of completion. This is not considered an accurate way
of determining the actual duration of action po-
tential but does provide an index of the time at
which the repolarization phase is completed.
In one experiment action potentials were recorded in a closed chest dog. The outer polyethylene tube was surgically sutured on the epicardial surface of the right atrium. A silver band
which served as an indifferent electrode was fitted
at the tip of the outer tube (fig. IB). After the
animal recovered from anesthesia, the inner polyethylene tube containing an insulated silver wire
was inserted into the sutured outer tube and
suction was applied to the interior of the inner
tube. Then, series of action potentials were recorded beginning immediately after recovery
from the operation and up to 30 hours after the
operation.
Results
TIME COURSE OF REPOLARIZATION
Figure 2A illustrates an example of the data
obtained in a closed chest dog. The upper
FIGURE 2
Records from three experiments by the coaxial suction electrode method. A: Normal control
tracings in closed chest animal. Top is lead II ECG. B: Normal control tracings in open chest
animal. Lower two tracings are the monophasic action potentials. Rising phase of depolarization
was retouched. Note that the repolarization phase is not completed during the QRS complex.
C: Monophasic action potential obtained during vagal stimulation. Right vagus trunks were
stimulated at 20 cycles/sec for 5 msec at 20 v. Rising phase of depolarization was retouched.
Two potentials were obtained from both the right and left atrium. There was a remarkable
shortening of the repolarization phase of the right auricular action potential during vagal
stimulation. Repolarization was completed in the QRS complex only under this condition.
Time calibration, 100 msec; voltage calibration, 10 mv.
Circulation Retesrch. VoL XIX. Jnly 1966
ATRIAL REPOLARIZATION
99
TABLE 1
Average Duration of Action Potentials* and other Results* Obtained in Eight Dogs
Dog
no.
no.
P-R
interval
msec
25
40
45
50
65
45
50
60
118
113
105
104
136
132
123
92
Measurements
1
2
3
4
5
6
7
8
*M e a n
±4
±3
±8
±2
±2
±7
±2
±15
Duration of atrial monophasic
action potential
Pacemaker
Other
regions
region
msec
241 ±19
194 ± 10
161 ± 10
153 ± 6
194 ±12
225 ±23
194 ± 9
222 ±21
msec
228 ± 12
169 ± 15
185 ±13
150 ± 1
183 ±12
221 ±27
199 ±27
187 ± 7
Heart
rate
beats/min
149 ± 3
182 ± 7
182 ± 5
183 ± 3
148 ± 10
114 ± 7
133 ± 2
123 ±17
Intra-atrial
conduction
velocity
cm/sec
104 ±29
89 ±39
89 ±22
135 ±47
74 ±15
91 ±17
117 ± 36
—
•+• SD.
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tracing gives lead n ECG. The lower monophasic records were obtained from the right
atrial surface. The suction electrode method provides characteristically a stable base
line even in a closed chest dog. Therefore,
not only the onset of depolarization but also
the end of repolarization of the atrium can
be measured clearly.
In figure 2B theTnoridphasic potentials were
obtained from the open chest dog from
both the vicinity and the distal parts of the
pacemaker. The duration of the P-R interval,
duration of the atrial monophasic potential
and heart rate in the open chest experiments
are shown in table 1. The duration of the
monophasic action potential ranged from 153
to 228 msec in 16 determinations. The P-R
interval varied between 92 ± 15 msec and
136 ± 2 msec in 8 instances. It can be seen
that the P-R interval was much shorter than
the duration of the atrial action potential
and that the end of repolarization did not
coincide with the QRS spike. In the closed
chest animal, the remarkable reduction in
half duration of action potential could be
seen, but the completion of repolarization was
always found after the QRS spike.
In figure 2C, action potentials of both the
right and left atrium during right vagal stimulation are shown. A remarkable shortening
of the action potential duration of the right
atrium was observed with no concomitant
change in duration of that in the left atrium.
Such nonuniform distribution of vagal effects
Grculation Reje»rcfa, VoL XIX, July 1966
has been suggested previously,16 but our findings will be reported separately.
DEPOLARIZATION AND REPOLARIZATION AT
VARIOUS SITES OF THE ATRIUM
Many workers have explored the spread
of activation throughout the atrial tissue under
normal conditions by various methods, such
as the surface bipolar method18' 10~18 and the
intfacellulaf microelectrodeTnethodr19'20 The
former method is often unstable due to movement artifact and the application of the latter
is limited to isolated strips of atrial tissue.
However, as mentioned previously, the present method is very stable and can be used
to detect the time of onset of depolarization
and end of repolarization of a specific portion
of atrial musculature under the electrode.
An example of propagation of depolarization in one dog is illustrated in figure 3.
One electrode was fixed in the vicinity of
the pacemaker (A) and the other electrode
was moved to 14 different sites of the right
atrium. The observed time differences from
A to 10 sites are indicated by numerals in
figure 3. The isochronous lines show the wave
front of excitation at 5-msec intervals measured from point A. Owing to the vigorous
movement of the atrial tissue, precise measurement of the electrode distance during systole
was not expected, but the measurement was
found to be correct within an error of ± 1 mm
during diastole by using a double scale caliper. From these results the conduction velocity of excitation on the right atrial surface
was calculated. It ranged from 74 to 135
100
IRISAWA, NINOMIYA, SEYAMA
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polarization at site A, but repolarization at C
was 14 msec earlier than repolarization at A.
In figure 3-3, where the second electrode
had been moved to D, repolarization occurred
simultaneously. Finally in figure 3-4, where
the electrode had been shifted to E, both
depolarization and repolarization of site E
lagged behind those in A. Thus in this atrium
the repolarization at C was found to be the
fastest, and repolarization at A, B and D
occurred almost simultaneously. Then repolarization was completed at site E. These
results indicate that the pattern of spread of
depolarization is not identical to that of repolarization.
SPJtEAD OF REPOLARIZATION THROUGHOUT THE
RIGHT ATRIUM IN RELATION TO SPREAD OF
ACTIVATION
Depolarization and repolarization at various parts of
the atrium in one experiment. On the left is the diagram of the right atrium and the vena cava. S.V.C.,
superior vena cava; I.V.C., inferior vena cava. A, B,
C, D and E are the sites where the suction electrode
was placed. Monophasic tracings from these fwe
regions are given on the right. Time calibration, 100
msec. Isochronous lines indicate 5-msec intervals of
the wave front of depolarization. Numerals in the
diagram indicate the arrival time of excitation. For
further explanation see text.
cm/sec (mean 99.8 ± 18.9 SD cm/sec). The
mean conduction velocity in the right atrium
of each dog is shown in table 1, but the
conduction velocity was different according
to direction in the atrium. For example, in
figure 3 the velocity in the A to E direction
was the highest.
The process of repolarization differed from
site to site in the right atrium. In figure 3-1,
action potentials were recorded simultaneously from two sites (A and B), and though
the lag in depolarization at site B was 23
msec greater than A, repolarization was completed at approximately the same time. In
figure 3-2 where the second electrode had
been moved to C from B, depolarization at
C occurred 13 msec after the onset of de-
The pathways of atrial repolarization waves
were measured by the foregoing method and
are shown in the expanded diagram of the
right atrium (fig. 4). Depolarization and repolarization of eight different examples are
illustrated in figure 4A and B, respectively.
The isochronous lines indicate the approximate
location of the wave front at 10-msec intervals. In each figure about ten sites on the
right atrial surface were selected for sampling. It can be noted that the spread of
depolarization occurred in a similar manner
in all eight instances illustrated. It was confirmed that the wave of excitation started at
the S-A node and spread almost concentrically through the right atrial surface. Depolarization spread in the right atrial surface within about 20 to 40 msec. However, the pattern
of repolarization varied in each experiment.
For example, in dogs 1, 2, 3, 6, 7 and 8
repolarization did not start from the S-A
node region, indicating that the area of initial depolarization is not identical with the
area of the initial recovery. In dogs 4 and 5,
repolarization had patterns that were similar,
with respect to time course, to that of depolarization. These pictures indicate that
repolarization spreads in the right atrial surface within about 20 to 50 msec. This, of
course, varied with the size of the atrium,
but repolarization required a time slightly
longer than that of the depolarization process.
Circulation Roearch. Vol. XIX, JUIT 1966
ATRIAL REPOLARIZATION
B
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B
FIGURE 4
Diagram showing spread of depolarization (A) and
repolarization (B) in eight experiments. Isochronous
lines indicate 10-msec intervals. The center of depolarization is indicated by solid circles, and that of
repolarization is given by circles with cross. For explanation see text.
In one instance out of eight different experiments there were two regions where repolarization was completed relatively faster than in
any other region.
Discussion
Inasmuch as these experiments provided
data that are important for electrocardiography, discussion of the assumptions involved
in the present experimental technique is pertinent. Recent advances in electrophysiological
studies of myocardial cells have shown that
the duration of action potential of the single
heart muscle cell is affected by various factors,
such as difference in extracellular ionic
composition, heart rate, asphyxia, temperature,
and chemical substances.21-22
Gradation Roarch, Vol. XTX, July 1966
101
The effect of temperature appears to be a
predominant factor in the experiments reported here. Pipberger et al.28 observed continuous changes in polarity and configuration of
T waves when the heart was exposed to
room temperature. In our experiments the
temperature of the laboratory was maintained
at 25°C. The temperature of the heart surface
was measured and found to be about 32°C,
indicating that the heart was cooled by the
room air, and possibly by evaporation as well.
The temperature of the epicardium was monitored continuously by a small thermistor
sutured on the surface of the atrium in one
experiment and the change in surface temperature was found to be rather small during
the experiment (less than ± 0.1°C).
It has been known that Qio of the duration
of action potential has a value of 2 to 3 in
cardiac muscles.21 Therefore, the change in
conduction time of depolarization due to a
difference of 0.1°C falls within the range of
technical error in the present experiment.
However, a difference of 0.1°C should cause
a difference of 3 to 6 msec in duration of
the action potential. This difference must be
recognized as one of the factors responsible
for the variation in time required to complete
repolarization at various sites of the atrial
surface.
In the microelectrode technique the potential is obtained from a single uninjured
cell, but in the suction electrode method the
potential is recorded from an area about 0.59
mm2, and thus a large number of cardiac cells
must be involved. Through comparative
study of intracellular potential and injury potential, it is assumed in the present experiment that the rising phase of the monophasic
action potential is an indicator of arrival time
of depolarization and that the falling phase is
the time when the small area is repolarized.24'25
Owing to the small number of sampling
sites in each animal, a minor error is probably
introduced in the drawing of isochronous
lines on the right atrium. On the other hand,
increase in sampling sites will greatly damage
the myocardium, and this might induce
IRISAWA, NINOMIYA, SEYAMA
102
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changes in the action potential. Thus, in
this experiment the isochronous lines for both
the depolarization phase and the repolarization phase were drawn from the data obtained in about 10 selected sites on the right
atrium.
In table 1 the average duration of monophasic action potentials in the S-A node region
differs from that in other sites of the right
atrium. A statistical test of difference between
average durations for two sites (S-A node
and elsewhere) was made for each experiment
by analysis of variance. The test criterion is
the variance ratio F (5%) shown in table 2.
In four experiments the calculated F ratio
exceeded the critical value, and therefore the
suction method evidently separated the sitedependent variations in duration of action
potential (S-A node region and other sites of
the right atrium) from the sampling error
variation in the right atrium. However, in the
four other experiments the duration of action
potential in the pacemaker region did not
differ significantly from that in other regions
of the right atrium. This is considered to be
due to the large variation in standard deviation in the experiments reported here.
Despite these limitations, our experiments
TABLE 2
Variance Ratio Test of the Difference of Average
Duration*
Dog
1
2
3
4
5
6
7
8
Degrees of
freedom
1. 8
1, 14
1, 16
1, 18
1, 24
1, 16
1, 18
1, 26
show that the T. wave does not occur during
the QRS complex in the normal cardiac cycle
and that the area of initial depolarization
does not always become the area of initial
repolarization. This finding does not agree
with the current interpretation with regard to
the repolarization pattern. Further, the process of repolarization was found to occur
concentrically from an initial focus that is not
limited to any specific region of the atrium.
Although the process of repolarization does
not propagate, these results suggest that the
exploring electrode when placed on the body
surface would record the wave of repolarization as if it were spreading concentrically.
Since the process of repolarization was different from experiment to experiment, apparently
the process of repolarization is subject to
considerable spontaneous variation in individual cardiac cells.
Acknowledgment
The authors thank Mr. K. Joji and Miss S. Fukui
for editorial assistance.
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Repolarization Phase at Various Sites of the Right Atrium
HIROSHI IRISAWA, ISHIO NINOMIYA and ISSEI SEYAMA
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Circ Res. 1966;19:96-103
doi: 10.1161/01.RES.19.1.96
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