Download Electrophysiological Characteristics of Canine Atrial Plateau Fibers

Electrophysiological Characteristics of Canine
Atrial Plateau Fibers
By Perry M . Hogan and Larry D. Davis
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ABSTRACT
Right atria from dog hearts were immersed in Tyrode's solution with the
endocardial surface of the anterior wall exposed. Glass microelectrodes were
used to impale fibers in diSerent anatomical areas of this preparation. Electrical
characteristics of atrial plateau fibers located along the caval border of the
crista terminalis were compared with those of regular atrial fibers from other
sites. The former conducted at a rate (0.803 ±0.110 M/sec) two to three
times more rapidly than pathways composed of regular atrial fibers. A period of
supernormal excitability was demonstrated for plateau fibers but not for regular
fibers. Graded premature responses could be elicited in plateau fibers by both
electrical stimulation and propagated action potentials. Duration of the
effective refractory period of plateau fibers (196.1 ± 2.5 msec) was longer
than that of regular fibers (147.8 ± 5.4 msec). Plateau fibers required a lower
level of membrane potential (—62.1 ± 0.8 mv) to generate a propagated
action potential than did regular fibers (—65.5 ± 1.3 mv). Regular atrial fibers
could respond at faster rates to high frequency stimulation than plateau fibers.
KEY WORDS
conduction velocity
supernormal excitability
premature excitation
• Anatomical evidence for the existence of
extranodal specialized fibers in mammalian
atria was provided by the early work of
Wenckebach (1), Thorel (2, 3), and Bachmann (4, 5). More recently, James (6-9) and
others (10-14) have confirmed the presence of
specialized pathways in the atria of several
mammalian species. In each of these studies
fibers were found in the atria which had
certain histological characteristics similar to
those of ventricular Purkinje fibers.
Electrophysiological evidence for specialized atrial pathways was provided in the
studies of Eyster and Meek (15-19). They
From the Department of Physiology, Medical
School, University of Wisconsin, Madison, Wisconsin
53706.
This investigation was supported in part by U. S.
Public Health Service Grants 1-R01-HE-12780-07 and
1-R01-HE-13375-01 and grants from the Wisconsin
Heart Association and the Western New York Heart
Association.
Dr. Hogan's present address is Department of
Physiology, State University of New York at Buffalo,
Buffalo, New York 14214.
Received August 31, 1970. Accepted for publication
November 10, 1970.
62
effective refractory period
rapid frequency stimulation
showed that sinoventricular transmission
could be impaired to different degrees by
placing cuts along the borders of the sinoatrial
node. From this they postulated that specialized pathways exist which normally convey
the sinus impulse to the atrioventricular node.
Lewis and his co-workers (20, 21) argued
against this idea and in favor of the concept of
radial spread of the sinus impulse with
uniform velocity through homogeneous atrial
muscle. More recent findings provided by
studies in which cellular transmembrane
potentials were recorded have shown the
presence of extranodal specialized atrial fibers
in the hearts of several species (22-34).
Recent work from this laboratory has
presented evidence for a type of specialized
fiber in the right atrium of the dog (31, 34).
The contour of the action potential of these
fibers is remarkably similar to that of ventricular Purkinje fibers. Because of a prominent
plateau during repolarization (phase 2), the
fibers were called atrial plateau fibers. Such
fibers were found consistently along the venous border of the crista terminalis. This is the
Circulation Research, Vol. XXVIII,
January 1971
63
ATRIAL PLATEAU FIBERS
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approximate location of the posterior internodal tract described by James (6-9), and it
was suggested (34) that atrial plateau fibers
might compose this tract.
In the present study, certain electrophysiological characteristics of these atrial plateau
fibers were determined. Conduction velocity
was measured along the pathway composed of
platetau fibers and was compared with similar
measurements along several pathways of the
right and left atria composed predominantly
of regular muscle fibers.
Childers et al. (33), in their study of the
specialized fibers of Bachmann's bundle,
concluded that the presence of a phase of
supernormal excitability during repolarization
was the most "reliable and distinctive" feature
of these specialized fibers. In the present
study, atrial plateau fibers were shown to have
a period of supernormal excitability. Finally,
we studied the response of plateau fibers to
premature excitation and measured the duration of the effective refractory period of both
plateau and regular atrial muscle fibers.
Methods
Hearts were excised from dogs anesthetized
with sodium pentobarbital (30 mg/kg, i.v.). A
right atrial tissue preparation as described in an
earlier report (34) was dissected from the heart
and pinned under slight tension to a paraffin
block in the tissue bath. Fibers located along the
caval border of the crista terminalis were studied
in the experiments described below. Based on the
contour of the action potential they have been
designated as atrial plateau fibers (34). In many
preparations, a free-running strand of tissue
similar to the false tendons of the ventricle
connected the caval border of the crista terminalis
with the upper pectinate muscles of the anterior
free wall of the right atrium. The fibers
comprising the free-running strand were found to
be plateau fibers and were included in this study.
The electrical characteristics of plateau fibers
were compared with those of regular atrial muscle
fibers located in the crista terminalis, pectinate
muscles, or epicardial surface of the left atrial
appendage.
Tyrode's solution equilibrated in a reservoir
with 95% oxygen and 5% carbon dioxide flowed
continuously through the tissue bath at a rate of
25 ml/min. The composition of the solution in
millimoles per liter was: NaCl 137, dextrose 5.5,
KC1 2.7, Cad 2 2.7, MgCl2 0.5, NaH2PO4 1.8,
Circulation Research, Vol. XXVIII,
January 1971
NaHCOg 25. Temperature in the tissue bath was
maintained at 35° to 37°C but remained
constant during each experiment. The pH of the
solution was 7.3 to 7.4. Transmembrane potentials of atrial fibers on the endocardial surface of
the preparation were recorded using glass
microelectrodes filled with 3M KC1. Details of the
recording system used have been described
previously (34).
Conduction velocities along linear pathways in
five anatomically distinct areas of the atria were
determined by the method described by Paes de
Carvalho et al. (22). Briefly, drive stimuli, 5 msec
in duration and at a rate of 95/min, were applied
to one end of the pathway under study through a
unipolar stimulating electrode. One microelectrode was inserted into a cell close to the
stimulating electrode. The onset of the action
potential at this site served as a fixed reference
point from which to time the arrival of the
impulse at distal sites. In an alternative procedure, this reference electrode remained extracellular and the stimulus artifact was used as the
reference point. A second microelectrode was
used as an exploring electrode to impalefibersof
the same type at increasing distances away from
the reference electrode. The type of fibers,
composing each pathway studied was based on
inspection of the action potential recorded at each
impalement site. The distance which separated
the two microelectrodes was read to 0.1 mm from
a vernier scale attached to the micromanipulator
used to position the exploring microelectrode. The
upstrokes of the action potentials from both
proximal and distal sites were displayed at a fast
oscilloscope sweep speed and photographed. For
analysis these records were projected on the
screen of a Benson-Lehner X-Y film reader. The
distance between the upstrokes of the two action
potentials was determined and converted to the
time in milliseconds required for excitation to pass
between the two recording sites. These data were
plotted against the distance which had separated
the two microelectrodes, and the slope of the
resulting curve, computed using the least-square
equation for linear regression, was taken as the
conduction velocity along the pathway. Analysis
of variance was used to test for the presence of
significant differences between the groups of
conduction velocities which were based on
anatomical location. Duncan's multiple range test
(35) was used to compare the mean of each
group with the mean of every other group and
thereby locate the site of significant difference
between groups.
To test for supernormal excitability in atrial
plateau fibers, the method of Childers et al. (33)
was used. A special stimulating and recording
64
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circuit was employed1 which made it possible to
stimulate and record through the same intracellular microelectrode. Microelectrodes with relatively
low tip impedance (5 megohms) were used to
facilitate passage of stimulating current. For these
experiments, the tissue was driven at a constant
rate (95/min) by administering drive stimuli
(SI) through a unipolar surface electrode. A test
stimulus (S2) could be applied through the
intracellular microelectrode at any preselected
time after a given drive stimulus. Initially, S2 was
delivered midway in the period of electrical
diastole, well after the maximum diastolic
potential was attained. The amplitude of S2 was
increased until it succeeded in producing a
premature response with each application. Then
its amplitude was lowered just enough so that it
repeatedly failed to cause a response. The interval
between SI and S2 then was reduced by
increments until S2 successfully produced a
response. With further reduction of the interval
between SI and S2, a point was reached when
the latter stimulus again failed to produce a
premature action potential. Subsequently, S2 was
abruptly repositioned to mid-diastole, where it
again failed to elicit responses.
Responses to premature excitation and duration
of the effective refractorv period of both plateau
and regular atrial muscle fibers were measured
by administering cathodal drive and test stimuli
directly to the tissue under study. The fiber
studied was always within 1 mm of the unipolar
stimulating electrode. A test stimulus, 5 msec in
duration and two times the diastolic threshold,
could be applied at any time during a driven
action potential. Initially, the test stimulus was
given during the plateau or early phase 3 of the
action potential and elicited no premature
response. On subsequent trials the test pulse was
moved by small increments progressively later in
the cycle. Six to eight drive stimuli were allowed
in succession before application of a single test
pulse. Two methods were used to determine if the
test response was propagated. When the earliest
test response was of relatively large magnitude
and depolarized to or beyond the line of zero
potential difference, it was assumed to be
propagated (36). The second method required
the use of a second microelectrode inserted into a
fiber located several millimeters from the stimulus
site. The end of the effective refractory period
was taken as the point at which an action
potential elicited by the test stimulus propagated
to the distal recording site (37). This method was
HOGAN, DAVIS
used in studies in which early test stimuli elicited
graded responses.
The ability of the fibers to respond to rapid
rates of stimulation was determined by applying
stimuli at progressively shorter cycle lengths.
Cycle lengths of 630, 500, 430, 320, 250, 200,
160, and 100 msec were used. Starting with the
longest cycle length, stimuli were applied for 5second intervals at progressively shorter cycle
lengths. Records were taken continuously during
the entire determination by moving the film past a
vertically deflecting oscilloscope beam.
Results
CONDUCTION VELOCITY
Conduction velocity was measured along
linear pathways in five areas of the right and
left atria. Four pathways located on the
endocardial surface of the right atrium were
(1) along the free-running strand, (2) along
the caval border of the crista terminalis,
(3) along the middle or auricular border of
the crista terminalis, and (4) along the long
axis of a pectinate muscle. The former two
pathways were composed predominantly of
atrial plateau fibers while the latter two
pathways were composed of regular atrial
fibers. A fifth conduction pathway along the
epicardial surface of the left atrial appendage
was composed of regular atrial fibers.
Conduction velocities, as indicated from the
calculated slope of sequential activation time
versus linear distance plots, were determined
for 36 such pathways in 12 atrial preparations.
It was assumed that if the exploring electrode
was moved along a linear path in the same
direction as the wave of excitation that the
TABLE 1
Conduction Velocity Analysis (Duncan's MultipleRange Test)
M/sec
1. Epicardial left auricle
2. Pectinate muscle
3. Middle and auricular
crista terminalis
4. Free-running strand
5. Caval crista terminalis
N
.344
.431
.604
(5)
(5)
(10)
.786
.803
(4)
(6)
1
Designed and constructed by Mr. Joseph French,
Department of Rehabilitation Medicine, University of
Wisconsin, Medical School, Madison, Wisconsin
53706.
There is no significant difference at the 5% level
between the mean values for 1 and 2, or 2 and 3, or
4 and 5.
Circulation Research, Vol. KXVlll,
January
1971
ATRIAL PLATEAU FIBERS
65
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ACTIVATION
TIME (IT
Graphs of linear distance versus activation time measured for five anatomically distinct areas
of the canine atria: open stars = caval crista terminalis; triangles = free-running strand;
circles = middle and auricular crista terminalis; solid stars = pectinate muscle; half circles =
epicardial left appendage. The slope of each line indicates the conduction velocity for that
pathway. The data points for pathways composed predominantly of atrial plateau fibers are
fitted by solid straight lines. Those composed of regular atrial fibers are fitted by broken lines.
Demonstration of supernormal excitability in an atrial
plateau fiber. A: Test stimulus (S2) of subthreshold
strength placed midway in electrical diastole (the
stimulus artifact [arrow] seen during phase 4 indicates
the time of stimulation). B: S2 stimulus elicited a response during supernormal period. C: S2 stimulus was
ineffective when delivered earlier during repolarization.
In this and subsequent figures, time and voltage calibrations are indicated by the horizontal parallel black
lines. The vertical distance separating the lines equals
100 mv in all figures. In this figure the spikes on the
top line are at 200-msec intervals.
Circulation Research, Vol. XXVlll,
January 1971
coordinate points would show little scatter
and be fitted by a straight line (22). Six plots
were rejected for their excessive scatter and
nonlinearity. Table 1 summarizes the results of
the remaining 30 experiments. Analysis of
variance for the five conduction velocity
groups indicated a significant difference between groups. To locate the site of this
difference, Duncan's multiple-range test (35)
was employed at the 5% level. Table 1 shows
the ranked order of mean velocities and
further indicates where there was a significant
difference between groups. Conduction velocities along the free-running strand and caval
border of the crista terminalis composed of
plateau fibers were not significantly different
and were the fastest of all pathways measured. Regular muscle fibers composed the
other three pathways and conducted the impulse at a significantly slower rate (P < 0.005)
when compared with the specialized cells.
Figure 1 shows typical conduction velocity
plots for the five anatomical areas investigated.
66
HOGAN, DAVIS
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Premature responses observed during measurement of the effective refractory period in atrial
plateau fibers. The upper action potential of each record is from a plateau fiber close to the
stimulating electrode. The lower action potential of each record is from a plateau fiber several millimeters distal to the stimulating electrode. Application of the test stimulus is indicated
by the appearance of the stimulus artifact on the repolarization phase of the action potential.
A-E show graded responses in the proximal fiber as the test stimulus was given progressively
later during repolarization. The premature response at the stimulus site was eventually propagated to the distal fiber as shown in F. Discussion in text. Time spikes at 100-msec intervals.
SUPERNORMAL EXCITABILITY
It has been suggested that a period of
supernormal excitability is a characteristic of
specialized cardiac fibers (33). In the present
study, atrial fibers in the free-running strand
and along the crista terminalis were tested for
a period of supernormal excitability. The
presence of such a period during the terminal
phase of repolarization was demonstrated, as
shown in Figure 2. An intracellular stimulus
which failed to excite in mid-diastole (A)
always was successful when applied shortly
before complete repolarization (B), then
again failed when applied earlier during phase
3 (C). Similar results were obtained in 17
fibers from five hearts studied. It was not
possible to test for supernormal excitability in
regular atrial fibers because the amount of
current which could be passed through the
microelectrode was inadequate to produce
excitation of these fibers at any point in the
cycle.
RESPONSES TO PREMATURE STIMULATION
In these experiments, cathodal stimuli were
applied at various intervals during phase 3 of
the action potential. Figure 3 shows the
typical response of plateau fibers to this
procedure. The earliest detectable response
usually occurred midway during phase 3
repolarization and consisted of a depolariza-
tion of small magnitude with slow rising
velocity and short duration (A and B). When
the test stimuli were given progressively later
in the cycle, at higher levels of membrane
potential, the test responses had proportionately larger magnitudes, rising velocities and
durations (C-E). Such responses are called
graded responses and conduct with decrement
(38). Figure 3 (A-E) shows that the graded
responses failed to propagate throughout the
preparation, as indicated by the lack of a test
response in the distal fiber. Eventually, a point
was reached during the cycle at which a
premature response elicited in the proximal
fiber propagated to the distal recording site
(F). This signaled the end of the effective
refractory period in the proximal fiber as
described below. Action potentials with normal contour were obtained only after full
recovery of the membrane potential to the
maximum diastolic level.
In some experiments graded responses were
not observed and the earliest test response
obtained was of relatively large magnitude
(Fig. 4). Experiments of this type were
utilized in studies of the effective refractory
period presented below. In other experiments,
as shown in Figure 5, early test stimulation
resulted in a response which occurred only
after a long latent period (Fig. 5A). This
Circulation Research, Vol. XXVlll,
January 1971
ATRIAL PLATEAU FIBERS
67
D
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FIGURE 4
Determination of the effective refractory period of atrial plateau fibers. A: Trial of test stimulation given while the fiber was still refractory. B: When the test stimulus was positioned a
few milliseconds later in the cycle a large magnitude response was obtained, signaling the
end of the effective refractory period. C and D: Same phenomenon in a plateau fiber in
another preparation. Graded responses were not observed in the fibers shown in this figure.
Time spikes at 100-msec intervals.
FIGURE 5
Premature responses elicited in an atrial plateau fiber. A: Effect of a test stimulus given during
early phase 3. After a long latent period a nearly normal response occurred. As the test stimulus was applied progressively later during repolarization (B-E), the test responses occurred
after shorter latent periods and initially were graded in nature. Time spikes at 100-msec
intervals. See text for discussion.
response occurred at a high level of membrane
potential and had an almost normal contour.
When test stimuli were applied later in the
cycle (B-E), graded responses as described
above were obtained after short latent periods. This result appears identical to the
"paradoxical event" described by Kao and
Hoffman (38) in their studies of graded
activity in Purkinje fibers.
Graded responses also could be obtained in
plateau fibers being stimulated by propagated
action potentials. In the experiment shown in
Circulation Research, Vol. XXVlll,
January 1971
Figure 6, both drive and test stimuli were
administered to regular atrial tissue. One
microelectrode was located in a regular fiber
close to the stimulating electrode (lower
trace). A second microelectrode was located
in a plateau fiber at a distance (upper trace).
Early test stimulation produced a largemagnitude action potential in the regular
fiber, but no response occurred in the plateau
fiber. During subsequent trials, the test
stimulus was given later in the cycle and
elicited small-amplitude depolarizations and
68
HOGAN, DAVIS
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FIGURE «
dHTanlL7T%
eZh record X T
T ye
1 t™,
aPPhed
\°
rf m
fibBT
CmSed
thB TegUhT
PWduCed
by
«**
a
^opagated action potential The
Shown in th
° Attorn trace of
fiber
2 1 7u u
^
' "^
^-magnitude
action potential in the
regular fiber but no response in the plateau fiber (top trace). As the test stimulus u>al alied
progre^vely later in the cycle (B-E), the propagated potential of the regular Zr eTcHed
p
Ziz:zorwith
progressivdy Urm mamitude in the
ature
test
**•» ^- T>™SPt:t
vuhe elicited the series of rapid re-
* "
finally action potentials with more normal
features in the plateau fiber. It is evident that
graded responses in plateau fibers can be
elicited by propagated action potentials and
thus are not a phenomenon produced only by
electrical stimulation.
One final observation made during these
studies is of interest. In several preparations, a
single premature stimulus resulted in more
than one extra response. Examples of this
effect are shown in Figure 7. Similar observations have been made in studies of ventricular
muscle and Purkinje fibers (39).
DURATION OF THE EFFECTIVE
REFRACTORY PERIOD
The effective refractory period (ERP) is
defined as the shortest interval between two
propagated action potentials (40). The ERP
Circulation Research, Vol. XXVlll,
January 1971
ATRIAL PLATEAU FIBERS
69
±5
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Determination of the effective refractory period of regular atrial fibers. The upper action
potential is from a regular atrial fiber close to the stimulating electrode. The lower action
potential is from a regular fiber at a distance. The application of the test stimulus is indicated
by the stimulus artifact seen during repoUtrization. A-E show graded premature responses in
the proximal fiber as the test stimulus was moved progressively later in the cycle. The end
of the effective refractory period for the proximal fiber was signaled by the appearance of
the propagated response in the distal fiber. (F). Time marks at 100-msec intervals.
160 I
200
100
I
160
FIGURE 9
Determination of the ability of regular atrial fibers (A) and plateau fibers (B) to respond at
rapid frequency. The numbers indicate the stimulus cycle length in milliseconds. The vertical
black bars indicate a change in cycle length. Time spikes at 100-msec intervals.
of both plateau and regular atrial fibers was
measured in the present experiments. Forty
experiments were performed on plateau fibers.
Records from typical experiments are shown
in Figures 3 and 4. The ERP of plateau fibers
persisted until the membrane repolarized to —
62.1 ±0.8 (mean±SE) mv. The duration of
the ERP in these experiments was 196.1 ± 2.5
msec. The ERP of regular atrial muscle fibers
was determined in 14 experiments. The level
of membrane potential needed in these fibers
to obtain propagated action potentials was —
65.5 ±1.3 mv. Duration of the ERP for
regular fibers was 146.8 ±5.4 msec. Records
from an experiment with regular atrial fibers
are shown in Figure 8.
Statistical comparison of duration of effective refractory periods for the two fiber types
showed a significant difference (P<0.005).
Circulation Research, Vol. XXVlll,
January 1971
There also was a small but significant
difference (P<0.025) in the level of membrane potential required to give a propagated
response in each type of fiber. Other observations indicate that the refractory period of
atrial plateau fibers is longer than that of
regular muscle fibers. In most hearts it was
possible to obtain full-sized action potentials
in regular atrial fibers. (Figs. 6A, 7D, and 7E)
before any response was observed in plateau
fibers. Also, when the ability of both types of
fibers to respond to rapid frequencies of
stimulation was determined, it was found that
regular atrial fibers could respond at faster
rates than plateau fibers. In 7 of 11 preparations, regular atrial muscle fibers responded to
every stimulus given at 600/min. In six of
eight similar experiments on plateau fibers, the
fiber ceased to respond to every stimulus when
HOGAN, DAVIS
70
the rate was less than 600/min. Records from
representative experiments are shown in Figure 9.
Discussion
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Atrial plateau fibers possess several characteristics exhibited by specialized conducting
and impulse-generating fibers. For example, in
an earlier study (34) it was demonstrated that
atrial plateau fibers have electrical features
similar to ventricular Purkinje fibers. In
particular, they exhibit a long plateau phase
during repolarization and inherent slow diastolic depolarization. The maximum rate of
depolarization during the upstroke of the
action potential of plateau fibers is greater
than in other fibers. Further, plateau fibers are
relatively resistant to inactivation by elevated
extracellular potassium. Additional evidence
of the specialized nature of atrial plateau
fibers is indicated by the results of the present
study. Measurements of conduction velocity,
supernormal excitability and refractoriness of
plateau fibers favor this concept.
It was suggested earlier that atrial plateau
fibers, by virtue of their rapid upstroke
velocity, might be capable of rapid impulse
conduction between S-A and A-V nodes.
Actual measurements of conduction velocity,
as presently done, support this suggestion.
The most rapid linear conducting pathway
measured was along the caval border of the
crista terminalis and was composed of plateau
fibers. This finding further demonstrates that
in addition to regular atrial muscle fibers the
crista terminalis contains specialized conducting fibers. Their anatomical location corresponds to the bundle first described by Thorel
(2, 3) and later by James (6-9) as the
posterior intemodal tract. Rapid conduction
along atrial plateau fibers correlates with the
findings of several investivators (22, 24, 27, 29,
41, 42) that excitation passes more rapidly
along the crista terminalis than through
adjacent atrial muscle. Regarding the absolute
values for conduction velocities reported in
this study, it was shown that atrial plateau
fibers conduct the impulse two to three times
more rapidly than regular atrial fibers. This
agrees with the recent findings of Holsinger et
al. (43) who showed, using cardiac electrograms, the same relative difference between
areas containing the intemodal tracts and
areas composed predominantly of regular
atrial fibers. It should be noted that although
plateau fibers conduct at relatively fast rates
they do not compare with the very fast rates
reported for ventricular Purkinje fibers (44).
The intemodal pathways in the atrium are
shorter than the Purkinje network of the
ventricles and may not require the rapid
conduction velocity of the latter fibers to
synchronize atrial contraction and to provide
preferential activation of the atrioventricular
node.
Another electrical feature of atrial plateau
fibers is a period of supernormal excitability.
In the present study, it was shown that
supernormal excitability exists in the plateau
fibers of the free-running strand and crista
terminalis. This phenomenon has also been
observed in the specialized fibers of Bachmann's bundle (33) and in ventricular Purkinje fibers (45) and thus provides additional
evidence for the presence of specialized
Purkinje-like fibers in the canine right atrium.
The effective refractory period of atrial
plateau fibers was consistently longer than
that of other fibers. This difference is due
primarily to delayed repolarization caused by
the plateau phase. It is not due to the
difference in level of membrane potential
required to obtain propagated responses
because plateau fibers regained excitability at
a lower level of membrane potential than
regular fibers. This difference tends to reduce
the disparity in length of refractory periods
between the two fiber types. The measured
limits of the refractory period are dependent
upon the characteristics of the stimulus used
to produce premature excitation (46). In this
study, to ensure valid comparisons, stimuli
with identical characteristics of duration and
intensity were used for determinations on both
types of fibers. Two additional observations
substantiate the directly measured difference
in refractoriness between the two fiber types.
First, in several experiments, non-plateau
Circulation Research, Vol. XXVIII,
January 1971
71
ATRIAL PLATEAU FIBERS
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fibers showed full-sized action potentials
before any response was observed in plateau
fibers. Second, in experiments in which the
ability to respond to rapid frequencies of
stimulation was determined, plateau fibers
usually ceased to respond at lower stimulation
rates than did other fibers.
The latter type of experiment is very similar
to that introduced by Dawes (47) to measure
duration of the refractory period. We have
shown by direct measurement that the canine
right atrium contains two types of fibers with
markedly different electrophysiological characteristics—in particular, with respect to duration
of refractoriness. This raises the question of
which type of fiber is being evaluated. If the
stimulus was applied only to plateau fibers,
the observed maximal rate of response would
be slower and the duration of the refractory
period longer than if it was applied to other
fibers. For this reason, it seems reasonable to
propose that the site of atrial stimulation
should be the same in control and experimental determinations of refractoriness when this
technique is used.
The difference in refractoriness between
plateau and regular fibers is similar qualitatively to that known to exist between Purkinje
fibers and ventricular muscle fibers (37, 38).
In tissue preparations containing both types of
fibers, it usually is possible to obtain largemagnitude premature action potentials in
ventricular fibers before similar responses can
be obtained in Purkinje fibers (37-39). In
addition, when excitation of a Purkinje fiber is
produced by action potentials propagated
from ventricular muscle, local responses are
frequently produced in the Purkinje fiber. In
the present study we observed similar behavior with plateau and regular atrial fibers. Such
responses may be of significance in the genesis
of atrial arrhythmias.
Several observations made in this and
previous studies may aid in understanding the
origin of atrial arrhythmias. As noted above,
atrial plateau fibers have several electrophysiological characteristics in common with Purkinje fibers. Some investigators believe that
the origin of ventricular arrhythmias can be
Circulation Research, Vol. XXVIII,
January 1971
explained best in terms of changes in excitability and conductivity of the latter fibers.
Detailed discussion of the evidence for this
idea can be found in the reviews of others
(48-50). We have shown previously (34) that
plateau fibers have inherent slow diastolic
depolarization which can be enhanced by
catecholamines to the point of spontaneous
discharge of action potentials. Therefore it is
possible that in intact animals atrial plateau
fibers are responsible for development of atrial
ectopic foci. In the present study, it was
shown that premature excitation of plateau
fibers, whether caused by electrical stimuli or
propagated action potentials, produced graded responses. Such responses propagate slowly
and decrementally (37, 38), and it is believed
that the resulting delay or block of conduction
is favorable for circus movement and reentry
of excitation (48-50).
A final point regarding the possible role of
plateau fibers in atrial arrhythmias is based on
the assumption that these fibers compose the
posterior internodal tract. Sherf and James
(51) considered the function of the three
internodal tracts in transmission of excitation
to the A-V node. They postulated that
excitation would reach the A-V node first over
the anterior or middle tracts or both rather
than over the posterior tract. This is logical in
view of the relative length of the different
tracts and the likelihood that conduction
velocity along each tract is similar (43). They
postulated that in the normal situation excitation might pass retrograde for a distance along
the posterior tract. One could speculate that in
normal hearts the long refractory period of
atrial plateau fibers would insure that excitation does not ascend any great distance over
the posterior tract. If the situation should arise
that conduction velocity over the posterior
tract increased concomitantly with a reduction
of duration of refractoriness, the entire
pathway might become responsive to retrograde excitation. James (6) has called attention to the fact that the internodal tracts form
a circuitous pathway around the orifices of the
venae cavae. Movement of the impulse around
such a circuit long has been proposed to
72
HOGAN, DAVIS
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explain the atrial arrhythmias of flutter and
fibrillation (46). One condition which may
produce the changes in conduction velocity
and refractoriness stated above is vagal
stimulation or application of acetylcholine.
This agent hyperpolarizes the membrane,
increases the overshoot, and markedly shortens duration of the action potential of plateau
fibers (34). The tendency of atrial arrhythmias to occur during parasympathetic activity
or application of acetylcholine is well known
(46). We recognize that these proposals are
tentative but believe them to be consistent
with the current state of knowledge concerning structure and function of the internodal
tracts.
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Electrophysiological Characteristics of Canine Atrial Plateau Fibers
PERRY M. HOGAN and LARRY D. DAVIS
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Circ Res. 1971;28:62-73
doi: 10.1161/01.RES.28.1.62
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