Conduction of the Cardiac Impulse
I. DELAY, BLOCK, A N D ONE-WAY BLOCK I N DEPRESSED
PURKINJE FIBERS
By Paul F. Cranefield, Herman O. Klein, and Brian F. Hoffman
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ABSTRACT
Depressed excitability and responsiveness were created in excised bundles of
canine Purkinje fibers. A segment 8 mm long was depressed by being encased
in agar containing 47 mM K + , the ends of the bundle outside the agar
remaining normal. Either normal end could be excited through extracellular
electrodes. Action potentials were recorded by intracellular microelectrodes at
each end and within the depressed segment. Conduction velocity within the
depressed segment fell as low as 0.05 m/sec. Abnormalities of impulse
transmission through the depressed segment included delay, 2:1 block, higher
degrees of block, rate-dependent block, and block showing the Wenckebach
phenomenon. Asymmetries of conduction seen included one-way block. Action
potentials in the depressed segment were of low amplitude and showed slow
upstrokes. Variations in action potential duration occurred in the depressed
segment when conduction failed or was very slow and when impulses were
dropped. Delay in conduction too great to result simply from a slow upstroke is
attributed to summation of excitatory events across regions of block in a
syncytium of cells. The results prove that conduction delays great enough to
permit re-entry can occur in short segments of Purkinje fibers subjected to high
K+.
KEY WORDS
ventricular conducting system
Wedensky inhibition
ventricular extrasystole
parasystole
fibrillation
myocardial ischemia
The assumption that very slow conduction
•
and one-way block can occur in relatively
short stretches of cardiac fibers is relied on in
explanations of various forms of re-entrant
arrhythmias and of entry and exit block in
association with parasystolic foci (1-3). Such
slow conduction has been shown in the A-V
node by direct recording from single cells of
the node (4-7). Slow conduction has also
From Rockefeller University, New York, New York
10021, and the Department of Pharmacology of the
College of Physicians and Surgeons of Columbia
University, New York, New York 10032.
The research was supported by a Grant-in-Aid to P.
F. Cranefield from the New York Heart Association
and by a grant from the National Institutes of Health
(Grant HE 11994-02). Dr. Klein was a Special U. S.
P. H. S. Postdoctoral Fellow during the period in
which this research was conducted. Dr. Klein's present address is the Department of Medicine, Albert
Einstein College of Medicine, Bronx, New York
10461.
Received August 5, 1970. Accepted for publication
November 24, 1970.
Research, Vol. XXVIII,
February 1971
exit block
entry block
mechanism of arrhythmias
transmembrane potentials
been demonstrated by recording mechanical
activity in strips of turtle heart depressed with
high external K + (8, 9); Drury (10) showed
slow conduction in atrial muscle, depressed by
cold or by pressure, by recording electrograms
in normal and depressed tissue. Most studies
of conduction in depressed cardiac fibers using
single cell recording of transmembrane action
potentials (11-16) have been carried out on
tissue uniformly depressed throughout its
length.
It seemed to us that the best model for the
abnormal conduction which might arise during organic or functional depressions of
cardiac muscle of the sort seen in clinical
disorders of rhythm would be a bundle of
cardiac fibers with a segment of depressed
excitability intervening between two segments
of normal tissue. We have devised a technique
which permits the recording of electrograms
or single cell action potentials at each end of a
199
200
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depressed segment as well as within the
depressed segment. The effects found include
short delays, very long delays, one-way block,
rate-dependent block, variable block in which
conduction may fail in one direction and be
2:1 in the other, variable block in which
conduction may be 1:1 with delay in one
direction and show the Wenckebach phenomenon in the other direction, and complex
changes in the duration of the action potential
and refractory period that depend on the
presence or absence of block, on the presence
of slow transmission, and on the effect of rate
on duration which is manifest after a dropped
impulse.
Methods
Experiments were conducted on isolated preparations of canine cardiac Purkinje fibers obtained
from animals anesthetized with pentobarbital
sodium. Isolated false tendons (obtained from the
cavity of the right or left ventricle) and attached
bits of ventricular muscle were pinned to the wax
bottom of a tissue bath and perfused with a
modified Tyrode solution (16) gassed with 953!
O 2 and 5% CO 2 , maintained at 36 or 37C, and
flowing at 30 ml/min through a chamber whose
volume was 20 ml. Changes in the composition of
the Tyrode solution to depress the fiber in the
bath were made by adding appropriate amounts
of 1 M KC1 to the stock solution.
The tissue used had the configuration shown in
Figure 1. Stimuli were brief rectangular pulses
which were isolated from ground and delivered to
the preparation through fine Teflon-coated bipolar
silver wire electrodes (Fig. 1). Transmembrane
potentials were recorded through intracellular
microelectrodes filled with 3 M KC1 and having a
d-c resistance in Tyrode solution of 20 to 30
megohms. Symmetrical junctions of 3 M KC1AgCl-Ag coupled the microelectrodes to the
preamplifiers and the tissue bath to ground. The
preamplifiers* provided high input impedance
and input capacity neutralization. Signals were
displayed on Tektronix oscilloscopes (564 or
565)** and photographed. Records of transmembrane potentials were calibrated by injecting
known signals of 50 or 100 mv between the bath
and ground.
A dissecting microscope and ocular micrometer
were used to measure the tissues and interelectrode distances. For most experiments part of the
false tendon was encased between two layers of
•NF-1, Bioelectric Instruments.
"Model 564 or 565, Tektronix.
CRANEFIELD, KLEIN, HOFFMAN
FALSE TENDON
Diagram showing the arrangement of the tissue, stimulating and recording electrodes, and agar. M =
ventricular muscle. St, Ss = stimulating electrodes
at the proximal and distal ends of the preparation. P, M, and D = intracellular recording electrodes at the proximal end of the preparation, in
the middle of the agar, and at the distal end of the
preparation. The stippled area represents the agar
which is shown in oblique view in the insert. The
dimensions of the slabs of agar were as follows: L, =
8 to 12 mm, W = 4 to 5 mm, and H = 2 to 3 mm.
A groove was made in one side of each slab to accommodate the size and shape of false tendon employed.
agar made up in either normal or high-potassium
Tyrode solution. The agar was prepared as
follows: To 100 ml of Tyrode solution, 4 g of
agart were added. The agar was dissolved by
bringing the mixture to the boiling point and was
then poured into a Petri dish to cool. From the
solidified layer slices about 3 mm thick were cut
to be applied to the fibers in the manner
described. To make high K + agar, K + was added
in the form of 1 M KC1, and water was added to
bring the solution back to isotonicity. The high
K + agar therefore differed in over-all ionic
composition from normal Tyrode solution. The
high K + agar was made as follows: To 100 ml of
normal Tyrode solution were added 4 g of agar, 6
ml of 1 M KC1, and 34 ml of distilled water.
Thus, apart from the agar, there were 140 ml of
solution with an approximate ionic composition as
tBacto-Agar, Difco Laboratories, Detroit, Michigan.
Circulation Research, Vol. XXVIII,
February 1971
201
DELAY, BLOCK, AND ONE-WAY BLOCK
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follows: N a + 108 mil, K + 47 HIM, C h 150 mM,
HCO S - 8.6 mM, H 2 PO 4 - 1.3 mM, Ca++ 1.9 HIM,
Mg++ 0.36 mM, dextrose 4 mM. The level of
C a + + and HCO3~ is questionable since much of
each is lost from solution when the solution is
boiled to dissolve the agar. Apart from high K + ,
therefore, the agar used to induce depression
contain elevated Ch, a somewhat lowered Na + ,
and less than normal Ca + + and HCO3~.
As shown in Figure 1, the agar encased the
central segment of an unbranched false tendon
(Fig. 1). Stimuli were delivered to normal tissue
5 mm or more distal to the ends of the agar.
Microelectrodes were inserted into single fibers at
various points within the agar and also at selected
distances from its ends. For most experiments
three intracellular electrodes were used simultaneously.
In many of our records, the effects produced by
conduction in one direction through the depressed
segment differed from the effects produced by
conduction in the other direction. Some of the
asymmetries were "artifacts" which derived from
the method. If one of the electrodes used to
record from outside the depressed segment was
very near the agar, the cells from which it
recorded were exposed to a slightly elevated
potassium by their proximity to the high K + agar.
In addition, the end of the bundle near the point
at which fluid exited from the bath was exposed
to slightly higher K + since the fluid which had
flowed over the agar had slightly more K + than
the fluid entering the bath.
TERMINOLOGY
We use the terms "upstream" and "downstream" with reference to the direction of
conduction of the impulse. Downstream refers to
the fiber beyond the recording electrode in the
direction in which the impulse is traveling;
upstream refers to that part of the fiber from
which the action potential has traveled to reach
the recording electrode. The words distal and
proximal are used to identify the two ends of the
preparation and refer to the normal direction of
spread of the impulse in the heart. The distal end
of the segment is therefore that part originally
nearer the ventricle. We occasionally refer to
"transmission of the impulse" to avoid the
implications of all-or-nothing propagated depolarization associated with the terms conduction and
action potential.
Results
Figure 2 shows the results of an experiment
in which one electrode was placed in each end
of the fiber outside the ends of the agar while
a third electrode was inserted into a fiber
Circulation Research, Vol. XXVlll,
February 1971
A
The effect of high K+ agar on conduction in a bundle
of Purkinje fibers. The agar-encased segment was
8 mm long, and the K+ concentration in the Tyrode
solution was 7.0 mM. The upper trace (d) was obtained from an electrode beyond the distal edge of
the agar; the middle trace (m) was obtained at the
center of the depressed segment; the lower trace (p)
was obtained outside the proximal edge of the agar.
In A the fiber was driven from the proximal end; in B
it was driven from the distal end. In each instance
conduction through the depressed segment is slow,
and the action potential within the depressed segment shows a slow upstroke. Calibration: time 200
msec, voltage 100 mv.
within the agar. In the absence of the
depressed segment, conduction velocity in the
bundle would be about 2 m/sec. In Figure 2A
the over-all apparent conduction velocity is
0.12 m/sec. When the impulse traverses the
agar in the opposite direction (Fig. 2B), the
apparent over-all conduction velocity is 0.18
m/sec. An obvious correlate of the slow
transmission is seen in the transmembrane
action potentials recorded from the center of
the high K + agar, which are diminished in
amplitude and duration and show a slowed
rate of depolarization. In this experiment
neither of the electrodes placed outside the
agar was particularly close to the agar. The
somewhat slowed upstroke seen at the distal
site in Figure 2A is presumably the result of
the fact that the cell from which we recorded
had been excited by an action potential that
had been depressed by passage through the
agar. It will be seen that the entering action
potentials are normal in all traces. Possible
causes for inequality of conduction velocities
in the two directions are considered in the
discussion.
To verify the assumption that the effect
described is chiefly caused by high K + , we
studied fibers encased in agar containing a
202
CRANEFIELD, KLEIN, HOFFMAN
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normal concentration of K + . Action potentials
obtained immediately after the agar was
applied were approximately normal in amplitude and configuration. Two hours after
application of the agar, no deterioration was
seen, apart from a very slight acceleration of
repolarization. In fact, we saw a slight
increase in resting potential, upstroke velocity,
amplitude, and overshoot, i.e., an improvement in the condition of the fiber that
probably resulted from the fact that the
bundle had recovered from whatever slight
damage it suffered during the manipulation
needed to place the agar layers in position.
The slight acceleration of repolarization may
have resulted from a minor inadequacy of
oxygenation or a minor accumulation of K+
that had leaked from the fiber.
In Figure 3 the fiber is encased in an agar
containing a normal concentration of K + . The
upper trace is recorded from a fiber within the
agar; the lower trace is recorded from a fiber
outside the agar which is directly exposed to
the bathing solution. In Figure 3A the bathing
solution was normal. In Figure 3B and C, the
K + in the bathing solution has been raised to
10 mM and in Figure 3D to 12 mM. The effect
of elevated K + in the bathing solution is
manifested more markedly in the fiber in the
solution than in the fiber in the agar. The fiber
within the agar is thus subject to the effects of
changes in the ionic composition of the bath,
but it responds to such changes to a lesser
degree and with a lapse of time when
compared with the fiber in the bathing
solution. This observation shows that diffusion
across the agar does occur and suggests that
the agar acts as a thick unstirred layer and is a
B
A
N
N
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1
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- —
—1
D
c
N
Effect of the concentration of K+ in the bathing solution on a fiber encased in agar containing a normal concentration of K+ (4 mM). The upper trace was recorded from a fiber within
the agar and the lower trace from a fiber exposed to the flowing Tyrode solution. Zero
reference potentials for both electrodes are shown in B. For A the preparation was perfused with Tyrode solution containing 4.0 mM K+,• the records in B and C were obtained
immediately and five minutes after increasing the K + concentration in the Tyrode solution
to 10.0 mM and those in D immediately after increasing K + to 12.0 mM. Calibration grid:
50 msec and 40 mv.
Circulation Research, Vol. XXVIII,
February 1971
203
DELAY, BLOCK, AND ONE-WAY BLOCK
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"reservoir" of ions at the concentration originally present in the agar. Thus, the agar does
not by itself impair excitability of the fibers
encased within it. The agar is fairly freely
permeable to ions, and the original ionic
composition of the agar itself dominates but
does not entirely determine the ionic composition at the bundle within the agar. It seems
reasonable to conclude that the high K+ agar
sandwich acts on fibers encased within it
chiefly by exposing them to an environment
high in K + .
The effect of the high K+ agar on the
upstroke of the action potential is seen at a
A
B
1
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FIGURE 4
Transmembrane action potentials showing upstroke
velocity and conduction time before (A and B) and
after (C and D) encasing a segment of an isolated
false tendon in a high K+ agar. K+ concentration
in the Tyrode solution was 6 mM. The depressed segment was 10 mm long. The proximal trace (p) was
obtained 0.5 mm from one end of the agar and the
distal trace electrode (d) 2.0 mm from the other end.
The middle trace (m) was obtained 4 mm from the
distal margin of the agar. Under control conditions,
before application of the agar, when the distal end
of the fiber was stimulated, the conduction velocity
was 1.8 m/sec (A); when the proximal end was stimulated, the conduction velocity was 2.1 m/sec (B).
After depression effected by the agar, when the distal
end was stimulated, conduction (C) velocity was
0.66 m/sec, and the upstroke of the action potential
within the depressed segment was markedly slowed;
when the proximal end was stimulated (D), the conduction velocity was 0.7 m/sec, and the upstroke in
the depressed segment was slowed. The stimulus
duration is different in D, as is the sweep speed.
Calibration grid: for A, B, and C 5 msec and 40 mv,
for D 10 msec and 40 mo.
Circulation Research, Vol. XXVIII,
February 1971
fast sweep speed in Figure 4. The records in
Figures 4A and 4B were obtained before
application of the agar; the preparation was
stimulated at the distal end for A and the
proximal end for B. The action potentials
recorded at the proximal and distal sites show
reasonably rapid upstrokes and normal amplitudes (116 and 124 mv). Conduction time
between the electrodes was 7 msec (A) and 6
msec (B). After the preparation had been
encased in the agar, conduction time increased
to 19 msec when the distal end was stimulated
(Fig. 4C) and to 33 msec when the proximal
end was stimulated (Fig. 4D). The action
potential recorded from the distal end of the
preparation in Figure 4C shows little change
from the control, while action potentials
recorded from within the agar and at the
proximal end show a marked decrease in rate
of rise and in amplitude. When the distal end
was stimulated (Fig. 4C), conduction velocity
had decreased from the control value of 1.8
m/sec to approximately 0.66 m/sec; when the
proximal end was stimulated (Fig. 4D), the
conduction velocity had fallen from the
control value of 2.1 to 0.38 m/sec.
If a sufficient length of the false tendon is
encased in agar of sufficiently high K+
content, an action potential which propagates
from a normal segment of the false tendon
into a depressed segment will deteriorate
progressively until propagation fails (Fig. 5).
The deterioration is progressive in part
because loss of K+ to the flowing Tyrode
solution makes the concentration of K+ lower
at the edges than at the center of the agar.
Resting potential thus decreases progressively
with increasing distance from the edge of the
agar. As shown in Figure 5, the resting
potential recorded from a fiber outside the
agar and 4 mm from its edge is 85 mv, that
recorded 0.5 mm outside the agar is 76 mv,
that recorded inside the agar and 1.5 mm from
the edge is 60 mv, and that recorded 4 mm
within the sandwich is 40 mv. From a resting
potential of 60 mv, the fiber generates a small,
slowly rising action potential of short duration; at a resting potential of 40 mv, there is
only a small response.
204
CRANEFIELD, KLEIN, HOFFMAN
A
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)
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y
f
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FIGURE 5
Complete failure of conduction in a segment of false tendon depressed by high K+ agar.
The preparation was driven from the proximal end, and records were obtained from fibers
located 4.0 mm proximal to the agar (A), at the edge of the agar (B), l.S mm inside the agar
(C), and 4.0 mm inside the agar. Each record shows a zero reference potential. Calibration
grid: 20 mv and 100 msec.
A sufficient degree of asymmetry to give rise
to one-way block is shown in Figure 6. The
action potential in the upper trace shows some
depression prior to entering the agar; that
depression results in part from proximity to
the agar and in part from the fact that K + was
elevated in the bathing solution to a level of
lOmM. The entering action potential shows a
slow initial step. The response recorded from
within the agar is much more depressed. It
shows a long slow step followed by a more
rapid (but still very slow) upstroke. Were
there no record from further downstream one
could not say whether this action potential
propagated further or not, but the record
obtained in the lower trace shows that
excitation was indeed transmitted through the
depressed region. This action potential also
shows a slow initial step followed by a more
rapid but still abnormally slow upstroke. The
speed of the upstroke and the amplitude of
this action potential leave little doubt that it is
capable of further propagation. In Figure 6B,
however, we see that when the impulse
invaded the depressed region from the other
direction, it failed to emerge from the
depressed area to excite fibers at the other
end. The entering action potential has a faster
upstroke and approximately the same amplitude as the action potential shown in the
upper trace of Figure 6A, although it is much
shorter. A small and slowly rising depolarization is seen within the agar, and only a very
small and slowly rising electrotonic response is
seen beyond the agar. A response of such slow
rise time and low amplitude is sometimes
associated with propagation in a depressed
fiber; in a fiber bathed in normal Tyrode
solution, such a response indicates failure of
forward conduction. In this situation, therefore, conduction in one direction is 1:1 with
delay, while there is total block of conduction
in the other direction.
Figures 7A and 7B show bidirectional total
Circulation Research, Vol. XXV'III, February 1971
205
DELAY, BLOCK, AND ONE-WAY BLOCK
A
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A
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p
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d
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B
m
Slow conduction through a depressed segment in one
direction and failure of conduction in the other direction. The segment encased in agar was 8 mm long,
and the K+ concentration in the Tyrode solution was
10.0 mM. The upper trace (p) was obtained from a
site 1 mm outside the agar; the middle trace (m) was
obtained at the center of the depressed segments;
the lower trace (d) was obtained 4.5 mm beyond the
distal edge of the agar. When the proximal end was
stimulated (A), marked delay of transmission occurred,
but an action potential of good amplitude emerged
from the far end of the depressed segment. When the
distal end was stimulated (B), the action potential
emerging from the depressed segment was of very
low amplitude, very slow rise time, and very short
duration and was almost certainly incapable of propagation (see text). Calibration grid: 50 mv and 200
msec.
block. There is asymmetry since the response
in the middle trace is much larger for the
direction of conduction shown in Figure 7B
than it is for the direction of conduction
shown in Figure 7A. In addition, a visible
deflection is seen at the site beyond the
depressed area in Figure 7B while none is
Circulation Research, Vol. XXVIII,
February
1971
seen at the other end when the impulse travels
in the opposite direction (Fig. 7A). About one
minute later, at essentially the same driving
rate, transmission in one direction is 1:1 with
marked delay (Fig. 7C), while in the other
direction transmission is 2:1 (Fig, 7D). The
middle trace of Figure 7C shows an interesting phenomenon. A long slow step precedes
the more rapid deflection in each instance, but
until the last two records on the strip, the
rapid upstroke in the middle trace occurs after
the rapid upstroke seen in the fiber beyond
the depressed area. In the last two records,
however, the rapid upstroke seen in the
depressed fiber definitely precedes the rapid
upstroke seen beyond the depressed area. This
shift in the relative timing of the upstrokes is
associated with an increase in the total delay
within the depressed area.
When conduction is in the other direction
(Fig. 7D), there is not only 2:1 block, but the
greatest delay occurs between the site within
the. depressed area and the fiber beyond the
block. This finding suggests that the major
slowing occurs before the site within the agar
while in the other direction it occurs after the
site in the agar. In Figure 7D one sees that the
2:1 block is associated with a slow deflection
preceding the rapid upstroke when there is
transmission; when there is no transmission,
only the slow deflection appears.
In the experiment shown in Figure 8, both
electrodes are outside the agar. The action
potentials shown in the upper trace of Figure
8A are essentially normal when they are
excited by conduction through fibers outside
the agar; when they are excited by transmission of the impulse through the agar (Fig. 8B,
upper trace), the upstroke is notably slowed,
and the plateau assumes an abnormal shape.
Similarly, the action potential recorded at the
other end of the agar is reasonably normal
when excited by conduction through fibers
outside the agar (Fig. 8B, lower trace)
although the upstroke is slow, probably
because of proximity to the high K + agar.
When excitation reaches this site by transmission through the agar, the upstroke is further
slowed, and the plateau is shortened (Fig. 8A,
206
CRANEFIELD, KLEIN, HOFFMAN
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FIGURE 7
Bidirectional complete block (A and B) changing to 1:1 conduction with delay in one direction (C) and 2:1 block in the other direction (D). The segment encased in high K+ agar was
10.0 mm long, and the K+ concentration in the Tyrode solution was 10.0 mM. The upper
trace (d) was recorded 4 mm beyond the distal edge of the agar; the middle trace (m) was
recorded within the depressed segment 4 mm from its proximal end; the lower trace (p)
was recorded 2 mm before the proximal edge of the agar. When the preparation was driven
from the proximal end (A) and the distal end (B), there was complete block between the
driven end and the end beyond the depressed segment. One minute later, when the preparation was driven from the proximal end (C), conduction with great delay occurred on a
1:1 basis; when it was driven from the distal end (D), 2:1 block was seen. Calibrations:
time 400 msec, voltage 100 mv.
lower trace). Figure 8C shows transmission of
excitation in the same direction as shown in
Figure 8A, but the driving rate has been
increased. As a result of the increased rate,
block has appeared. In the record shown, one
transmitted impulse is followed by three
which are not transmitted and then by
another which is. Figures 8A and 8C thus
show an excellent example of rate-dependent
block. Figure 8C also shows a striking
variation in duration of the entering action
potential, which is short when it advances into
a depressed area and is blocked and which is
long when transmission in the forward direction occurs. This effect is discussed in greater
detail below (Fig. 9). The results shown in
Figure 8D provide a further striking example
of asymmetry since at an even higher driving
rate than that shown in Figure 8C, but with
conduction in the opposite direction, transmission is 1:1. The records resemble those seen
with transmission in the same direction at a
much slower driving rate shown in Figure
8B.
The experiment shown in Figure 9 was
obtained from the preparation used in Figure
8. Each of the first eight pairs of action
potentials depicted in Figure 9A shows
marked delay; this delay increases for the last
two transmitted action potentials, which show
a change in both upstroke and duration. The
delay in the last transmitted impulse corresponds to essentially the full duration of an
action potential and to an apparent conduction velocity of 0.05 m/sec; the next impulse is
blocked. Similar long delays are seen in
Figures 9B and C.
Figure 9 shows remarkable delays and also
Circulation Research, Vol. XXVIII,
February 1971
DELAY, BLOCK, AND ONE-WAY BLOCK
A
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Bidirectional 1:1 conduction with delay changing to
4:1 block in one direction and 1:1 conduction in the
other direction. The depressed segment was 8.0 mm
long; the K+ concentration in the Tyrode solution
was 7.0 mM. The upper trace (p) and the lower trace
(d) were obtained from recording sites outside and at
opposite ends of the depressed segment. The recording
electrodes were symmetrical with respect to the agar
and were 13.3 mm apart. In A and B conduction is 1:1
when the proximal end (A) and the distal end (B)
are stimulated. In C stimulation of the proximal end
results in conduction to the distal end with 4:1 block.
In D stimulation of the distal end results in 1:1 conduction to the proximal end. The changes in action
potential duration resemble those seen in Figure 9.
Calibration: time 400 msec, voltage 100 mv.
shows the effect of the presence or absence of
forward transmission on duration. In Figure
9A the shortest entering action potential is
that corresponding to a dropped beat (the last
action potential in the upper trace of Figure
9A). Whenever the impulse is transmitted
through the depressed area, the entering
action potential shows a more marked plateau
than when the impulse is blocked. The
amount of delay increases gradually from the
first through the eighth pair of impulses, and
there is a corresponding variation in the
prolongation of the plateau of the entering
impulse. In this particular series of action
potentials, the prolongation of the plateau is
greatest when the delay is least (the first
action potential in the upper trace of Figure
9A). More marked changes in duration are
seen in Figure 9B. In the first action potential
Circulation Research, Vol. XXVIII,
February 1971
207
of the upper trace of Figure 9B, a marked
prolongation is seen, accompanied by transmission through the depressed area. The
prolongation is so great that the next action
potential is markedly shortened, not only by
failure of forward transmission, but also by
simple prematurity. In the third and fourth
action potentials one sees, presumably, the
effect of absence of forward transmission,
unaffected by prematurity. Similar change in
duration, probably unaffected by prematurity,
can be seen in the action potentials of Figure
9C. When the impulse is transmitted during
this period of 2:1 block, the duration is much
greater than when the impulse is not transmitted. Similar effects of block or slow transmission on action potential duration can be seen
in Figure 6A (upper trace) and Figure 7C
(lower trace), as well as in Figure 8.
In Figure 10A, 1:1 transmission is seen, and
the maximum depression of upstroke velocity
is not seen within the depressed area but in
the normal solution beyond. Most of the delay
also is seen between the site within the agar
and the emerging action potential. A very
small increase in the driving rate results in 2:1
block (Fig. 10B). This very slight increase in
rate still produces reasonably normal activity
within the agar, but beyond the agar normal
action potentials alternate with low-amplitude, slow deflections which correspond to the
electrotonic spread from a blocked site. A
further slight increase in rate, as shown in
Figure IOC, reveals that when 2:1 block is
established, the upstroke of the action potential in the lower trace (beyond the agar) is
much more rapid than when transmission was
1:1 as in Figure 10A. This improvement in the
action potential results from the fact that the
effective rate of excitation is lower because of
the 2:1 block. The same fact explains the
prolongation of the plateau. These changes
may be seen in Figure 10B but are more
marked in Figure IOC
In the experiment shown in Figure 11, when
the distal end of the fiber was stimulated,
there was complete failure of transmission
(Fig. 11A). A small electrotonic potential is
seen within the agar, a very small irregular
CRANEFIELD, KLEIN, HOFFMAN
208
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FIGURE 9
Conduction with long delay and variable block showing marked changes in action potential
duration. The experimental conditions were identical with those described in Figure 8 except that all records shown were obtained during drive of the proximal end. Conduction
delay in A increases from one pair of action potentials to the next until block results in the
final action potential in the upper trace, evoking no action potential beyond the depressed
segment. The relatively slow upstroke makes precise measurement of conduction time difficult, but the delays in the first eight pairs of proximal and distal action potentials in A are
approximately 185 msec, 190 msec, 195 msec, 200 msec, 205 msec, 215 msec, 235 msec, and
245 msec. The change in action potential duration seen with changes in conduction delay
in A and with block in B and C is discussed in the text. Calibrations: time 400 msec, voltage
100 mv.
deflection is recorded downstream from the
agar, but there is no sign of transmission.
When the other end was stimulated at the
same rate, transmission occurred with 2:1
block (Fig. 11B). The action potential of the
fiber near the stimulus shows a rapid upstroke,
some alternation in duration, and an irregular
humplike prolongation of the plateau which is
more marked when the impulse is transmitted
than when it is not. The response within the
agar shows a marked step followed by a
delayed upstroke whether or not impulse
transmission occurs. This observation suggests
that the site of block was downstream from
the recording site. The response corresponding
to the blocked impulse does, however, show a
Production of 2:1 block in a depressed segment. A
segment 8.0 mm long was encased in high K+ agar;
the K+ concentration in the Tyrode solution was
4.0 mM. The upper trace (p) was obtained from a
site 2 mm proximal to the edge of the agar; the
middle trace (m) was obtained at the center of the
depressed segment; the lower trace (d) was obtained
from a site 2 mm beyond the distal edge of the agar.
The preparation was driven only at the proximal end.
Conduction is 1:1 with delay in A; a slight increase in
driving rate induces 2:1 block in B, but the "blocked"
response emerging from the depressed area is significantly larger than that seen in C after a further slight
increase in the driving rate. The improvement in the
transmitted action potential in C as compared with
that in A is discussed in the text. Calibration: time
400 msec, voltage 100 mv.
Circulation Research, Vol. XXVIII,
February 1971
DELAY, BLOCK, AND ONE-WAY BLOCK
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Variable and asymmetrical block in a depressed segment. A segment 10 mm long was encased in a high
K+ agar; the concentration of K+ in the Tyrode solution was 6.0 m,it. The upper trace (p) was obtained
1 mm proximal to the edge of the agar; the middle
trace (m) was obtained at the center of the depressed
segment; the lower trace (d) was obtained 2 mm
beyond the distal edge of the agar. The bundle was
driven from its distal end in A, and no conduction
occurred to the far end of the depressed segment. In
B the preparation was driven from its proximal end,
and conduction with 2:1 block is seen. The complex
and variable block and delay seen during stimulation
of the distal end in C and D are discussed in the
text. Calibration: time 400 msec, voltage 100 mv.
less steep upstroke than that corresponding to
a conducted impulse; in addition, the response
corresponding to a conducted impulse shows
marked prolongation of its plateau when
compared with the response recorded when
the impulse does not propagate through the
depressed region. A barely detectable deflection is seen beyond the depressed region at
the time of the dropped impulse, whereas an
essentially normal action potential corresponds to the conducted impulse. The delay in
transmission is almost entirely accounted for
by the duration of the long slow step in the
response recorded within the depressed area.
In Figure 11C speeding up the drive rate
unexpectedly resulted in transmission in the
direction that showed complete block at a
Circulaticm Research, Vol. XXVlll,
February
1971
209
slower rate (Fig. 11A). The drive rate was
altered in an irregular manner during this
experiment, and the irregularity in the rhythm
results from that, not from spontaneous
activity. Figure 11C shows five entering
impulses, two of which are transmitted and
three of which are not. As in Figure 11B, the
delay can largely be attributed to the long
slow step seen within the depressed area;
when there is no transmission, only the step is
seen within the depressed area. The transmitted impulses in Figure 11D have some
interesting features. The total delay increases
from the first to the third impulse, and much
of the delay and much of the increase in the
delay are caused by the duration of the slow
step seen in the depressed area since the rapid
deflection in the depressed area and the rapid
deflection beyond the depressed area are
nearly simultaneous for the first two transmitted impulses. In fact, careful inspection
reveals that the upstroke of the action
potential beyond the depressed area precedes
the rapid upstroke seen in the depressed area
(as it did in Figure 7C and does less obviously
in Figures 11B and 11C). This might suggest
that excitation, or electrotonic spread, in
another fiber evoked the rapid upstroke
beyond the agar. An alternative interpretation
is considered in the discussion.
A complex example of asymmetrical block is
shown in Figure 12. When the bundle is
driven from one end, conduction is obtained
with 2:1 block (Fig. 12A). A slight alternation
in amplitude is seen in the responses within
the depressed area, but all are large enough
and show a sufficiently rapid upstroke velocity
to suggest that the point of actual block occurs
between the central and the downstream sites.
This interpretation is strengthened by the fact
that the blocked impulse shows a rather large
electrotonic spread beyond the block. When
the other end of the bundle is stimulated, 3:2
block alternates with 2:1 block (Fig. 12B).
The net block is thus 5:3, a lesser degree of
block than that seen in the other direction.
The 3:2 phase of the block in Figure 12B
shows the Wenckebach phenomenon of delay,
greater delay, and a dropped impulse. In the
210
CRANEFIELD, KLEIN, HOFFMAN
A
KAAAAAAAAAA
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OVJMXA^NJVAAJVAJ
Asymmetrical block in a depressed segment. A segment 10 mm long was encased in high
K+ agar; the K+ concentration in the Tyrode solution was 7.0 mM. The upper trace (d)
was obtained 3 mm distal to the agar; the middle trace (m) was obtained at the center of the
depressed segment; the lower trace (p) was obtained 2 mm proximal to the agar. When the
distal end was stimulated (A), conduction through the depressed segment was 2:1; when
the proximal end was stimulated (B), conduction was 3:2 and showed the Wenckebach phenomenon. Calibration: time 400 msec, voltage 100 me.
middle trace, recorded from the depressed
area, the response corresponding to the first
conducted impulse has a moderately slow
upstroke, the next one has a markedly slow
and somewhat notched upstroke, and that corresponding to the "dropped impulse" is of very
low amplitude. The total delay of the first impulse is 65 msec; that of the second is 150
msec. In the second impulse most of the delay
is between the central point and the downstream site. Thus, as in Figure 12A, most of
the delay occurs beyond the central electrode
no matter which way the impulse is traveling.
The second transmitted impulse of the
Wenckebach cycle arises from a slow depolarization, which in turn results from the very
slow rise time of the upstream impulse. If one
did not have records from other sites, one
would designate that action potential as
showing spontaneous depolarization and thus
as the action potential of an automatic fiber. A
similar action potential can be seen in Figure
13B below. Finally, the action potential
immediately after the dropped impulse is
longer than either of the impulses transmitted
during the Wenckebach cycle and has a more
marked plateau as well as a more rapid
upstroke.
Figure 13A also shows a 3:2 Wenckebach
cycle followed by a 2:1 cycle. Figure 13B
shows several such cycles recorded at a lower
speed to show the regular repetition of the
alternation between a 3:2 Wenckebach cycle
and 2:1 block. Attention is called to the
prolongation of the action potential within the
depressed segment immediately after the
dropped impulse. This prolongation is seen in
Figure 12, but it is seen more clearly in
Figures 13A and 13B. The action potential
following the dropped impulse is longer than
the action potential of either of the impulses
transmitted during the Wenckebach cycle and
has a more marked plateau as well as a more
rapid upstroke. The prolongation of this
CirculaUon Research, Vol. XXVIII,
February 1971
211
DELAY, BLOCK, AND ONE-WAY BLOCK
A
B
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Conduction showing the Wenckebach phenomenon in both directions. The agar-encased segment was 8 mm long, and the K+ concentration in the Tyrode solution was 7.0 mM. The
upper trace (d) was obtained from an electrode 4.5 mm beyond the distal edge of the agar;
the middle trace (m) was obtained at the center of the depressed segment; the lower trace (p)
was obtained 1 mm before the proximal edge of the agar. The proximal end was driven in A,
and conduction shows a 3:2 Wenckebach cycle followed by a 2:1 cycle. The distal end was
driven in B, and a 3:2 Wenckebach cycle regularly alternates with a 2:1 cycle. The same
time calibration indicates 200 msec for A and 400 msec for B. Voltage calibrations are each
100 mv.
plateau leads to the next beat being dropped,
giving rise to a cycle of 2:1 block. The
mechanism of block during the 2:1 cycle is
therefore different from that during the
Wenckebach cycle.
The duration of the action potential recorded on the upper trace of Figure 13B varies
according to whether or not the impulse is
transmitted through the depressed area, as
described above for Figure 9. The occurrence
of block and dropped beats thus affects the
duration of action potentials both proximal
and distal to the point of block in a way that
might give rise to very complex patterns of
change in excitability and responsiveness.
In the experiment shown in Figure 14, when
one end of the fiber was driven at a fairly
rapid rate, transmission with regular 2:1 block
was seen (Fig. 14A). A slight shortening of
the entering action potential associated with
downstream block is seen in the lower trace.
The transmitted action potential seen in the
upper trace is unremarkable apart from a
Circulation Research, Vol. XXVIII,
February 1971
Conduction with 2:1 block in one direction and more
complex and variable block in the other direction. The
preparation is that described in Figure 13. When the
proximal end is driven, excitation is transmitted
through the depressed segment with delay and 2:1
block. When the distal end is driven (B), the average
block is 5:3, and virtually every delay or block arises
by a different mechanism, as discussed in the text.
Calibrations: time 400 msec, voltage 100 mv.
212
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well-marked foot or slow early phase. In the
middle trace, during failure of transmission,
the response is of low amplitude, while during
transmission the response shows a markedly
slow but smooth upstroke uninterrupted by
striking notching or steps.
When the other end of the fiber is excited at
the same rate, transmission with variable
block is seen. In the strip shown in Figure
14B, block varies between 2:1 and 3:1. Of the
ten entering impulses shown, the first, third,
sixth, and eighth are transmitted. A slight
variation in amplitude and duration is seen in
the entering impulse according to whether or
not the impulse is transmitted through the
depressed area. The behavior of the area
within the agar is complex. A deflection, large
or small, can be seen associated with each
entering impulse, and the deflections are
described in the order in which they occur.
The first impulse shows a moderately slow
step followed by a somewhat faster upstroke.
The next impulse, which is not transmitted, is
a slow, low-amplitude deflection. The third
shows a much longer delay, a prolonged early
slow step, and a somewhat faster delayed
upstroke. The net delay of transmission in this
instance is longer than the duration of the
entering impulse. The fourth deflection in the
middle trace is of fairly high amplitude and
shows a steep enough upstroke to suggest that
it might be transmitted through the depressed
area. The electrical response produced by it
beyond the depressed area falls, however, in
the relative refractory period of the fiber
beyond the depressed area, producing a late
deflection in its action potential. This failure
of transmission may therefore reflect the
timing which allowed the impulse to arrive in
the refractory period. The fifth deflection is of
very low amplitude. Perhaps because of that
and because of the relatively long period of
little electrical activity, the sixth deflection
shows the highest amplitude and most rapid
upstroke of any seen in this tracing and is
transmitted with the least delay (although still
very great). Also, perhaps because of the
comparatively quiescent period preceding it,
this action potential shows a long plateau. The
CRANEFIELD, KLEIN, HOFFMAN
next deflection falls in that plateau, which
may explain why it is not transmitted,
although if it had progressed further downstream, it probably would have reached the
distal fiber during its relative refractory
period. The eighth deflection is much like the
first, and the ninth and tenth contain no
features not previously described for earlier
deflections. The action potentials recorded
beyond the depressed region show rather long
plateaus when compared to the action potentials recorded at the same site in Figure 14A,
presumably because partial block reduces the
effective rate. They also show small deflections
in their plateaus or in diastole corresponding
to electrotonic transmission from the depressed segment. This record thus shows delay
associated with a foot and a slow upstroke,
delay associated with a smooth slow upstroke,
block associated with a very small deflection
in the depressed region, block associated with
the entering impulse arriving during the
relative refractory period of the fiber in the
depressed region, and block associated with
the arrival of the impulse beyond the depressed region during the relative refractory
period of the action potential beyond the
depressed region.
The records shown in Figure 15 were
obtained from the same preparation shown in
Figure 10, driven at a rate slow enough to
permit 1:1 transmission of all driven impulses
in either direction to permit study of the
transmission of premature impulses. Premature stimuli were applied after each driven
response. The preparation was asymmetrical
with respect to its ability to transmit premature excitation. In Figure 15A a premature
stimulus applied to one end of the preparation
400 msec after the driving stimulus elicited a
slowly rising action potential (shown on the
upper trace) which gave rise to a similar
response in the depressed segment; it failed to
excite the next segment, causing only the
small, slowly rising response shown on the
bottom trace. When the stimuli were applied
to the other end of the bundle only 320 msec
after the driving stimulus, the premature
response (lower trace in Fig. 15B) spread
Circulation Research, Vol. XXVUI,
February 1971
213
DELAY, BLOCK, AND ONE-WAY BLOCK
A
B
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Asymmetry in the transmission of a premature impulse through a depressed segment. The
preparation is that described in the legend to Figure 13. A relatively late premature excitation of the distal end in A is transmitted more poorly than a relatively early premature
excitation of the proximal end in B. Calibration: time 400 msec, voltage 100 mv.
through the depressed segment and appears to
have successfully excited the next segment
(top trace in Fig. 15B). Repolarization is
more rapid in the records shown on the top
trace than in the records on the bottom trace,
and so differences in action potential duration
do not explain the unidirectional block and
asymmetry. The premature response shown on
the bottom trace in Figure 15B is more nearly
normal than that shown on the top trace in
Figure 15A; however, it elicits delayed, slowly
rising responses which arise from slow steps at
the other two recording sites. The unidirectional block of the premature response thus
cannot be attributed solely to differences in
the voltage-time course of the input signal.
The cause of the asymmetry and the general
problem of propagation of premature responses in depressed tissue will be considered
in detail in a subsequent paper.
Discussion
CHARACTERISTICS OF THE DEPRESSED SEGMENT
+
The high K agar does not uniformly
depress the fibers within the agar. The
concentration of K + varies with time since K +
diffuses out of the agar, and it varies spatially
since K+ diffuses out more rapidly at the ends
than in the center. The method does not,
therefore, provide a precise quantitative determination of the effects of a given level of
K+ uniformly applied to a segment of Purldnje
fibers. Nor does the method permit a precise
quantitative analysis of the effects of elevated
K+ on a single excitable fiber since a bundle of
Circulation Research, Vol. XXV111, February 1071
Purkinje fibers about 1 mm in diameter
contains from 5 to 15 fibers which are
intricately interconnected by tight junctions
and branches (17, 18). It might be difficult to
obtain conduction intermediate between normal conduction and complete block by
applying a wholly uniform depression along a
segment of fibers. In fact, the spatial and
temporal variability of the depression reveals
the peculiarities of conduction in a bundle
whose fibers are on the border between
conduction and block and thus resemble fibers
in the heart that are damaged and are neither
normal nor wholly unexcitable.
ASYMMETRY OF CONDUCTION
Nearly all of our records reveal some
difference between conduction in one direction through a depressed segment and conduction in the other direction. A single unbranched fiber, uniform in diameter and
uniform with respect to all other characteristics which determine excitability, might show
identical conduction velocity in each direction
(19-21). Neither the location and frequency
of branches and tight junctions nor the
diameter of the fibers in a bundle of Purkinje
fibers are symmetrical with respect to the
midpoint of any segment. Indeed, our control
experiments show small differences of conduction velocity according to the direction of
conduction. In addition, it is unlikely that our
method produces symmetrical depression, and
any asymmetry in the depression produced by
the high K+ agar would exaggerate pre-
214
existing asymmetries and create new ones.
The presence of conduction velocities or
degrees of block which differ according to the
direction of impulse transmission is thus not
surprising (13, 19).
DEPRESSANT EFFECTS OF HIGH K+
+
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A modest increase in K increases conduction velocity in Purkinje fibers (22, 23), but a
larger increase results in an increased threshold and in depression of the upstroke
velocity. Depolarization, elevation of threshold, and slowing of upstroke velocity, all
contribute to a reduction of conduction
velocity. Elevation of external K + increases
membrane permeability and reduces the space
constant (11, 23), diminishing the electrotonic
spread of the action potential which in turn
further depresses conduction velocity. These
effects explain much of the simple slowing of
transmission of the impulse.
The interposition, between two normal
segments, of a short segment of fibers severely
depressed by high K+ cannot be directly
compared with the uniform exposure of a long
bundle of fibers to high K + . A lesser elevation
of external K+ may suffice to create complete
block when an entire bundle is exposed to
high K+ because at no point in such a bundle
is the action potential normal. In the experiments in which a segment of the bundle is
encased in high K + agar, the impulse invading
that segment is essentially normal in amplitude and rate of depolarization since it arises
in fibers exposed to an essentially normal ionic
environment outside the agar.
EXCITATION WITH GREAT DELAY
Moderate slowing of transmission of excitation may reasonably be attributed to wellknown effects of high K + ; complete block is
readily explained in the same fashion. It is less
easy to explain transmission so slow that a
delay of as much as 200 msec occurs over a
segment only 8 mm long. Before considering
possible mechanisms one comment must be
made. The methods we have used enable us to
ascertain with certainty the presence or
absence of conduction through the bundle and
to determine with accuracy the delay in such
CRANEFIELD, KLEIN, HOFFMAN
transmission, while the action potential recorded from one cell within the depressed
area reveals the details of the delay or block in
that particular cell. We cannot assert with
certainty that the impaled cell reveals all of
the characteristics that determine delay or
block in the entire bundle. It is the family of
abnormal impulses recorded from within the
depressed area that reveals the various sorts of
abnormal activity which, alone or cooperatively, give rise to such effects as delay, variable
block, and one-way conduction in the entire
bundle. These sorts of abnormal activity are
discussed in the following paragraphs.
Conduction in the heart may be decremental (7, 14) so that the action potential
becomes progressively less effective as a
stimulus as it moves along the fiber, blocking
at a point where the fiber is still excitable but
the action potential is unable to excite it. Some
of the results in Figures 12 and 14 suggest the
presence of decremental conduction since
block occurs near the point of emergence and
remote from the point of entry into the
depressed area, no matter from which end the
impulse enters.
In Figure 9, however, the delay is very
great, and the upstroke is not only slow but
shows two or three steps of varying steepness.
In another type of record, responses are seen
in which a long, slow step levels off and is
then interrupted by a very delayed slow
upstroke (Figs. 6A, 7D, and 11D). Explanations for these responses depend on the fact
that the bundle contains several or many cells
syncytially interconnected by branches and
tight junctions. We did not study our preparations histologically. Such studies would be
useful, as would electron-microscopic studies.
In addition to these anatomical considerations,
any particular fiber or part of a fiber may well
be slightly more or slightly less depressed than
another fiber or part. At a given moment and
at a given level of external K + , one may see
propagation into a group of fibers, in some of
which block occurs, in others of which very
slow conduction occurs, and in others of
which decremental conduction occurs. An
action potential which reaches an area of total
Circulation Research, Vol. XXVIII,
February 1971
215
DELAY, BLOCK, AND ONE-WAY BLOCK
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block may, for example, contribute, by electrotonic spread to a downstream site, a step of
the kind seen in Figure 11D, while another
fiber conducting very slowly may contribute
the greatly delayed upstroke seen in the same
figure. This is consistent with the fact that in
2:1 block, as seen in Figure 14A, the step
alone is seen during block while the step plus
the delayed upstroke are seen when the
impulse is transmitted through the depressed
area.
The coalescence of two or three action
potentials in fibers which are severely depressed but which are still able to conduct
may explain records in which slow upstrokes
with more than one rate of rise are seen (as in
Fig. 9A). It is even possible that conduction in
all fibers may be blocked and yet the impulse
may be transmitted throughout the bundle as
a whole. That could arise if the electrotonic
spread across the region of total block in each
of two or three fibers were great enough to
bring to threshold one or more fibers downstream from the point of total block (20).
Although electrotonic effects. occur essentially
instantaneously, summation of the depolarization induced by them occurs throughout the
duration of the entire action potential. Moreover, electrotonic spread beyond a block
would occur only subsequent to the time spent
in slow conduction up to the point of block. In
this connection one may note that the
duration of the small deflections is shorter
than that of a normal action potential and
more nearly corresponds to that of an action
potential shortened by failure of forward
transmission.
The action potential of cardiac fibers may be
made up of two components, one of which has
a fast rise time and a short duration, the other
of which has a slow rise time and a long
duration (24-26). If this notion is correct
and if the slow component can propagate for
a short distance in the absence of the fast
component, certain of our observations could
be explained. The paradoxical aspect of
Figures 7C and 11D is that when the upstroke
seen within the depressed segment appears
later than the upstroke beyond the depressed
Circulation Research, Vol. XXVIII,
February 1971
segment, the over-all latency increases. This
might mean that excitation was transmitted in
a fiber other than that from which we were
recording and that excitation then returned
from beyond the depressed segment to evoke
the rapid upstroke in the impaled fiber. Yet
the slow component might be able to propagate for a short distance at a very low
conduction velocity and trigger a normal
action potential in the more excitable fiber
beyond the depressed segment. Were this so,
the appearance of the rapid upstroke within
the depressed segment would still result from
the retrograde depolarization of the depressed
segment by cells beyond it. Yet the actual
path of propagation would have been through
the fiber from which we recorded.
Finally, small-diameter branches which
connect one fiber to another might play a role.
Such branches might have a low conduction
velocity in the normal heart, and yet their
presence would never be revealed since they
would be excited at one end by the larger
fiber from which they emerge and soon
thereafter excited at the other end by the
larger fiber with which they merge; the action
potential in the fine branch travels slowly
from each end and dies by extinction in the
center of the branch. If such branches are able
to conduct in a high K + environment, slow
conduction in them might enable an impulse
to bypass a site of block in the larger fibers
and do so with a very low velocity.
DURATION OF THE ACTION POTENTIAL
We have found striking changes in action
potential duration as the result of changes in
rhythm and as the result of block or of very
slow transmission. Since the duration of the
refractory period depends on the duration of
the action potential, these changes are of
obvious importance. The effect of the absence
of forward propagation on duration is not
unexpected. If the action potential is studied
in situations in which block occurs or in which
propagation cannot travel for a long distance
because the fibers are very short, the action
potential is very short and may show no
plateau (19, 27, 28). Mendez (29) has shown
that block induced by a sucrose gap causes
216
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marked shortening of the action potential only
if a low resistance path bridges the gap. Such
a path is present in our experiments; it allows
current to flow extracellularly from the
unexcited segment of the fiber into the excited
segment. This flow assists in repolarization
since an unexcited segment acts toward an
excited segment exactly as does an external
anode (30), facilitating repolarization. The
passive spread of current from the plateau
upstream and downstream from the recording
site thus plays a role in determining the shape
of the plateau at the recording site. Both the
intracellular and the extracellular resistance
must be low to permit the above effects to
occur. If either is high, the length constant
will be small, and interaction between depolarized and repolarized segments will be
greatly reduced. Any flow of current which
tends passively to sustain depolarization will
also have an active effect since such a flow of
current will maintain a level of potential that
favors the ionic permeabilities characteristic of
the plateau (31).
While failure of forward propagation may
shorten the action potential, greatly slowed
forward propagation lengthens it. Some of the
records in Figure 9 show action potentials far
longer than those seen in the same fiber under
normal conditions; the extent of the prolongation varies with the delay. We assume that the
slow forward movement of the action potential enables its plateau to spread back
electrotonically to the recording site, thus
prolonging the plateau there by passive and
active mechanisms similar to those just described. The marked prolongation seen with
slowed forward transmission seems especially
likely to be a cause of block of subsequent
impulses. We have not determined the refractory period under these conditions. While it is
almost certain that refractoriness lasts as long
as the action potential, it is possible that under
abnormal conditions full repolarization may
not signal full recovery of excitability.
The marked prolongation of the first entering action potential in Figure 9B suggests a
remarkable mechanism for another kind of
block. The downstream block ordinarily keeps
CRANEFIELD, KLEIN, HOFFMAN
the duration of the entering action potential
short enough to permit a given drive rate.
Relief of the downstream block, permitting
transmission of the action potential, may
lengthen the upstream duration enough to
cause upstream block of the next impulse.
Such upstream block might, oddly enough,
then permit more premature re-excitation of
the fiber from upstream than would be
possible otherwise. Interaction of downstream
block, upstream duration, block of upstream
excitation via prolongation, and subsequent
possibly very premature re-excitation from
upstream could obviously play a complex role
in the behavior of a parasystolic focus with
variable entry and exit block.
If to the effects of a dropped impulse on the
refractory period of the next impulse we add
the effects of shortening and prolongation of
the action potential which result from block or
slowing of forward transmission (Fig. 9), the
prolongation which is seen with very slow
forward transmission and the shortening seen
with prematurity, as well as the possible
interactions of rhythm, block, and potential
unblocking, become complex enough to begin
to shed some light on what may occur in the
incessant re-entry associated with fibrillation.
Significance for Intact Heart
Our results show changes in the spread of
the impulse which provide reasonable mechanisms for certain disturbances of rhythm and
conduction associated with the effects of
disease, drugs, or both on the human heart.
PARASYSTOLIC RHYTHMS
To explain the existence and behavior of
parasystolic foci, it has been necessary to
postulate entry block and exit block. For the
typical parasystolic focus, entry block usually
is assumed to be complete while exit block
varies so that some, but not all, of the
impulses generated in the parasystolic focus
spread through the boundary and excite the
heart. Several of the records which we have
shown demonstrate just such properties:
complete block in one direction and partial
block in the other. Additional factors may be
needed for the existence of a typical parasysCircuUtion Research, Vol. XXVIII, February 1971
217
DELAY, BLOCK, AND ONE-WAY BLOCK
tolic focus, but we have demonstrated that the
conditions of exit or entry block can develop
in depressed Purkinje fibers.
WENCKEBACH PHENOMENON
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Partial and complete atrioventricular block
may occur in the common bundle (32). The
results shown in Figures 12, 13, and 14 suggest
that the Wenckebach phenomenon might also
occur in the common bundle. The Wenckebach phenomenon could thus result from the
properties of depressed Purkinje fibers rather
than from the properties of depressed fibers of
the atrioventricular node.
The observation that the dropped impulse
of the Wenckebach cycle is followed by a
lengthened action potential is easily understood in terms of well-known effects of rate
and rhythm on the duration of the action potential. The appearance of the Wenckebach
phenomenon in man is very commonly accompanied by a Wenckebach cycle alternating
with a 2:1 cycle. It is reasonable to assume that
the regular appearance of a 2:1 cycle following
the dropped beat of a Wenckebach cycle in
man has the same basis as that seen in Figures
12, 13, and 14.
The initial impulse of the Wenckebach
cycle is also preceded by a pause, the pause
created by the dropped impulse of the 2:1
cycle. Yet the initial action potential of the
Wenckebach cycle is not lengthened as much
as is the transmitted impulse of the 2:1 cycle
(see especially Fig. 13B). In a certain specific
sense there was less electrical activity preceding the first action potential of the Wenckebach cycle than preceding the first action
potential of the 2:1 cycle. The first action
potential of the 2:1 cycle is preceded by a
dropped impulse which in turn is preceded by
a transmitted action potential of slow upstroke, low amplitude, and reduced duration.
The first action potential of the Wenckebach
cycle is preceded by a dropped impulse,
which, however, is preceded by an action
potential of large amplitude, long plateau, and
relatively fast upstroke. This difference in the
total amount of depolarization of the fiber
during the two preceding beats may well
explain why the first action potential of the
Circulation Research, Vol. XXVIII,
February 1971
2:1 cycle is longer than the first action
potential of the Wenckebach cycle, even
though each is immediately preceded by a
dropped impulse.
BLOCK
Disturbances in conduction through the
common bundle, the bundle branches, and the
peripheral Purkinje fibers result in complex
changes in the electrocardiogram. Sometimes
conduction is impaired more after a long
diastolic interval than after a short one; a
mechanism has been described which might
account for this phenomenon (14). More
commonly, conduction is more severely impaired as the duration of diastole shortens. If
an impulse is very premature or if the rate is
very rapid, the impaired conduction can be
ascribed to incomplete repolarization. However, severe impairment of conduction, or
complete block, can occur at rates which
permit complete repolarization of the HisPurkinje system between each impulse. The
rate-dependent changes in conduction which
we have demonstrated in depressed segments
may provide an explanation for this type of
abnormality since in depressed segments inability to develop a propagated response often
lasts long after completion of repolarization
in the normal segment.
RE-ENTRANT RHYTHMS
In 1928 Schmitt and Erlange-r (9) were led,
by experiments in which they recorded the
mechanical activity of strips of turtle ventricle
depressed by K+ , to propose an ingenious
mechanism for re-entry (see Figure 9 of their
article). They did not, however, record the
electrical activity of their preparations. The
mechanism proposed by them requires two
conditions: great delay in the spread of the
impulse over a short distance and the presence
of unidirectional block. We have demonstrated that such conditions can be obtained in
depressed segments of Purkinje fibers, and we
assume that re-entry can be obtained in the
way postulated by Schmitt and Erlanger. We
believe, however, that re-entry more often
results from a mechanism that depends on
phenomena described in the following article
(33).
218
CRANEFIELD, KLEIN, HOFFMAN
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DELAY, BLOCK, AND ONE-WAY BLOCK
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Circulation Research, Vol. XXVIU,
February 1971
Conduction of the Cardiac Impulse: I. Delay, Block, and One-Way Block in Depressed
Purkinje Fibers
PAUL F. CRANEFIELD, HERMAN O. KLEIN and BRIAN F. HOFFMAN
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Circ Res. 1971;28:199-219
doi: 10.1161/01.RES.28.2.199
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