255
Canine Ventricular Arrhythmias in the Late
Myocardial Infarction Period
8. Epicardial Mapping of Reentrant Circuits
NABIL EL-SHERIF, RUTH ANN SMITH, AND KERRY EVANS
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SUMMARY We made simultaneous recordings from 48 bipolar electrodes to obtain epicardial isochronal maps during induced ventricular arrhythmias in dogs 3-5 days after ligation of the left anterior
descending artery. There was strong evidence of a reentrant circuit (RC) that was discernible largely
on the epicardial surface in 21% of ectopic beats that were analyzed. Epicardial recordings were of
limited value in analysing the arrhythmia in other beats. The reentrant circuit consisted of an arc of
conduction block around which the activation front advanced in a circular fashion at slow but uneven
speeds while the rest of the ventricle was activated by radial spread. The arc of conduction block
around which the RC was formed was usually functional in nature, since the same area of myocardium
was excitable at relatively long cardiac cycle lengths. Both the length of the arc of conduction block
which defines the length of the reentrant circuit and the degree of conduction delay were crucial factors
for the occurrence of reentry. A premature beat that initiated reentry resulted in a longer arc of
conduction block and slower conduction compared to one that failed to induce reentry. Circ Res 49:
255-265, 1981
IN 1925 Lewis wrote: "Though there may be little
reason any longer to doubt that circus movement
occurs in the ventricle, evidence on lines similar to
that obtained for the auricle is desired to complete
the proof." It was undoubtedly because of technical
difficulties due to the complex geometrical and electrophysiological characteristics of the ventricle that
detailed mapping studies of ventricular reentrant
circuits were not obtained. The feasibility of circus
movement in the ventricle was, however, demonstrated in studies by Schmitt and Erlanger (1928),
Sasyniuk and Mendez (1971), and Wit et al. (1972a,
1972b). More recently, El-Sherif et al. (1977a,
1977b) used a canine subacute myocardial infarction model to record electrical activity on the epicardial surface of the infarction during ventricular
arrhythmias. Here, reentrant circuits occurred partially or totally in ventricular myocardium deep to
the subepicardial layer and were not detected by
epicardial recordings. However, some reentrant circuits were almost totally limited to the immediate
subepicardial layer of muscle and hence accessible
to epicardial recordings. In the present study, we
used a multiplexer recording system similar to that
described by Wyatt and Lux (1974) to obtain mulFrom the Veterans' Administration and SUNY Downsute Medical
Centers, Brooklyn, New York, and Nora Eccles Hsmson CardiovascuUr
Research and Training Institute, University of Utah Medic»l Center, Salt
Lake City, Utah
Supported by the Veterans Administration ajid Program Project Grant
HL 13+80 and the Richard A. and Nora Eccles Harrison Fund for
Electrocflrdiographic Research.
Address for reprints: Nabil El-Sherif, M.D., Veterans' Administration
Medical Center, 800 Poly Place, Brooklyn, New York 11209.
Received July 28, 1980; accepted for publication January 14, 1981.
tiple simultaneous epicardial recordings in the canine model and to construct isochronal epicardial
maps during induced ventricular arrhythmias. The
study shows evidence of reentrant activation and
examines in detail the electrophysiological determinants of reentrant circuits in ischemic ventricular
myocardium.
Methods
We studied nine adult mongrel dogs 3-5 days
after ligation of the left anterior descending artery
just distal to the anterior septal branch. In all dogs
a transmural infarction was evident on gross postmortem examination. Details of the surgical procedure have been described elsewhere (El-Sherif,
1977a). Dogs were anesthetized with intravenous
sodium pentobarbital (30 mg/kg). A jugular vein
was cannulated for the administration of fluids, and
femoral arterial pressure was monitored through a
polyethylene catheter connected to a Statham
transducer. The sinus node area was crushed and
atrial or His bundle pacing was used to control
ventricular rate. Atrial pacing was achieved via two
bipolar hook electrodes placed on the right atrial
appendage. His bundle pacing was accomplished
through the electrodes on the catheter used to
record the His bundle electrogram. Both regular
pacing and premature stimulation were performed
using a programmed digital stimulator that delivered rectangular impulses of 1.5-msec duration at
approximately twice diastolic threshold. Reference
atrial and right ventricular electrograms were obtained from close bipolar hook electrodes.
CIRCULATION RESEARCH
266
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A grid of 48 close bipolar electrodes was constructed in six rows and eight columns by sewing
individual electrode wires onto a nylon stocking
designed to fit over the heart. The electrodes were
made of quadruple-insulated silver wire (0.005-inch
total diameter). The bipolar electrodes had an interpolar distance of 0.4 to 0.8 mm and the distance
between the centers of adjacent bipolar electrodes
was 6 mm. The diameter of the electrode grid was
approximately 3.6 x 4.8 cm. The grid was placed
over the infarction and boundary zones. As viewed
from the apex of the heart the top row of electrodes
was adjacent and parallel to the anterior descending
artery (Fig. 1). Positioning of the grid was guided
by an initial recording using a composite electrode
of approximately the same size as the grid but not
having the same arrangement of bipolar contact
points. The epicardial site from which a composite
electrode preferentially recorded continuous asynchronous spikes bridging the diastolic interval during certain repetitive patterns of ectopic ventricular
rhythm was identified and the grid was placed on
approximately the same site. In some experiments,
the grid could partially overlap the interventricular
septum, cardiac apex, and/or the lower obtuse margin of the left ventricle.
The multiplexed data-recording system sampled
the potentials from the 48-grid electrodes, a body
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VOL. 49, No. 1, JULY
1981
FIGURE 2 Display of selected close bipolar electrograms. Note the multiphasic and/or broad deflections
recorded at sites of conduction delay (F to I). The points
for computer measurement of activation times are shown
as vertical lines.
surface electrocardiogram (lead II), and atrial and
ventricular reference electrodes. The multiplexer
sampling interval of 250 fisec allowed a maximum
frequency response of the system of 2000 Hz. The
frequency response for the differential amplifier was
0.2-300 Hz. The multiplexed signals were recorded
on an IRIG group II, 7-channel magnetic tape recorder for later signal processing by a PDP 15
computer. The computer was programmed to carry
out bandpass filtering with a low frequency cut-off
of 12 Hz and a high frequency cut off of 250 Hz.
Each unfiltered electrogram was amplified and displayed along with its first derivative for the operator
to choose the points for computer measurement of
activation time using a vertical cursor line. Filtered
electrograms were used for illustrations. In electrograms showing a sharp intrinsic deflection, the maximum slope was taken as the moment of activation,
whereas in slow multiphasic M- or W-shaped deflections, the maximum peak of the signal was chosen (see Fig. 2). The sections of the recordings to be
analyzed were selected by reviewing the body surface electrocardiogram (ECG). Individual electrogram data were plotted for 500-msec intervals to
allow a continuous display of two to four R-R cycles
on the computer printout. Epicardial isochronal
maps were constructed at 10- or 20-msec intervals.
Some isochrone lines were interpolated in the absence of actual recordings of activation at 10- or 20msec intervals. These will be referred to in the text.
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FIGURE 1 Diagrammatic illustration of the 48 electrodes grid (numbered 5 to 52 on the computer printout).
The grid is placed over the infarction and boundary
zone adjacent and parallel to the left anterior descending artery (LAD). The double bars illustrate the usual
site of ligation of the LAD.
Figure 3 is a computer printout of the body
surface ECG in one experiment. In panel A the His
bundle was paced at a cycle length of 380 msec, and
a His bundle premature beat at a coupling interval
of 250 msec failed to initiate an ectopic rhythm. A
coupling interval of 230 msec (panel B) induced
ventricular tachycardia. Panel C shows the spontaneous termination of the tachycardia.
EPICARD1AL MAPPING OF REENTRANT CIRCUITS/El-Sherif and Smith
257
right border of the grid and collides with the first
activation wave. Conduction velocity of the first
activation wave front is approximately 0.72 m/sec,
although it varies slightly in different directions.
Figure 5A shows the epicardial map of the His
bundle premature beat with a coupling interval of
250 msec which failed to initiate the ectopic rhythm
(Fig. 3, panel A) and figure 5B shows the map for
the premature beat with a shorter coupling interval
of 230 msec which initiated the ventricular tachycardia in Figure 3, panel B. The map in A shows a
slightly irregular activation wave front that invades
the upper border of the grid 10-30 msec after the
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FIGURE 3 A computer printout of the surface electrocardiogram (lead II) in one of the experiments. The
figure illustrates initiation and termination of ventricular tachycardia during His bundle stimulation. See
text for detads. R-R intervals are measured in milliseconds.
Figure 4 illustrates the epicardial isochronal map
of the His bundle paced beat at a cycle length of
380 msec in Figure 3. Activation times are calculated from the stimulus artifact which precedes the
QRS complex in surface ECG by 30 msec. Electrode
site 5 is thus activated 10 msec after the onset of
QRS complex whereas most of the upper border of
the grid is activated 20 msec after the onset of QRS.
One activation wave spreads from the upper to the
lower border of the grid reaching the mid-lower
border 70 msec after the onset of the QRS complex.
Since QRS duration is 50 msec, this site is activated
20 msec after the end of the QRS in the surface
ECG. There is a second wave that invades the lower
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4 Epicardial isochronal map of the basic His
bundle paced beat at cycle length of 380 msec (the first
beats in Figure 3, panels A and B). See text for details.
In this and subsequent figures, isochronal maps are
constructed at 10-msec intervals.
FIGURE
FIGURE 5 A- Epicardial isochronal map of the His
bundle premature beat with a coupling interval of 250
msec that failed to initiate reentry (Fig. 3, panel A). B:
Epicardial isochronal map of the premature beat with
a shorter coupling interval of 230 msec that initiated
ventricular tachycardia (Fig. 3, panel B). Activation
times are measured from the stimulus artifact. Straight
lines with double bars represent areas of unidirectional
conduction block, x represents sites of tachycardia-dependent conduction block. The asterisk shows the site of
reexcitation. See text for details.
258
CIRCULATION RESEARCH
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onset of the QRS. The upper right border of this
activation front is blocked (straight lines with double bars) and the rest of the activation front spreads
slowly (isochrone lines are crowded) from the left
upper corner of the grid toward the right lower
border. There it is met by a separate activation
front that invades the right lower border of the grid.
This separate front shows slow conduction and
block at its upper border (electrode site 36 marked
by x's).
The epicardial map of the premature beat that
initiated the tachycardia (Fig. 5B) differs from the
one in panel A as follows: The major activation
wave front that invades the upper border of the
grid now shows a much longer continuous arc of
conduction block that extends across the upper and
left side of the grid. This arc probably has a slight
bulge at electrode site 10 where the block was
occurring beyond the upper border of the grid (the
straight line with double bars marked ?). The activation wave spreads slowly around the arc of conduction block across the grid from left to right
borders, then reactivates site 12 at the right upper
border of the grid (marked by an asterisk). This site
is reexcited 20 msec before the onset of the QRS
complex in surface ECG. The left upper border of
the grid is activated 10 msec after the onset of the
stimulated His bundle premature QRS complex,
and the slow spread of activation from left to right
along the lower border of the arc of conduction
block takes 200 msec. Thus the complete reentrant
cycle conduction time is 230 msec. This time corresponds to the coupling interval of the first beat of
ventricular tachycardia to the premature His bundle beat as shown in Figure 3, panel B. Since the
reentrant circuit is oblong rather than circular, the
epicardial circumference of the circuit is only
slightly longer than double the length of the arc of
conduction block around which the reentrant wave
front circulates. This gives a value of approximately
7.2 cm for the epicardial circumference of the reentrant circuit in panel B and 3.6 cm for the length of
the arc of conduction block that was used in the
circuit. It should be stressed that the part of the arc
of conduction block that is used in the circuit probably is smaller than the total arc of block created
by the His bundle premature beat. This is understandable because the slow activation front moving
along the lower border of the arc of conduction
block will break through and reactivate the myocardium on the other side of the block once the
refractory period of the myocardium at this site
expires. This probably occurs at electrode site 12
where the refractory period of the myocardium is
200 msec. The average conduction velocity along
the epicardial circumference of the reentrant circuit
is 0.35 m/sec. However, the circulating wave front
conducts unevenly around the arc of conduction
block. Thus conduction velocity along the upper
border of the arc of block is approximately 0.85 m/
sec, whereas along the lower border it is 0.22 m/sec.
VOL.49, No. 1, JULY 1981
Conduction velocity is as slow as 0.12 m/sec at
some points along the lower border of the reentrant
circuit. The map in panel B shows that the separate
wavefront that invades the lower right border of
the grid conducts at a slower speed compared to the
same front in panel A. This wavefront shows conduction block along its upper border (marked x)
and collides with the major activation front at its
left border. Some of the crowded isochrone lines at
the upper border were interpolated and illustrate
the marked slowness of conduction prior to block.
Figures 6 and 7 illustrate simultaneous electrograms from critical sites on the epicarcial maps in
Figure 5 and help to demonstrate the nature of both
slow conduction and conduction block necessary for
successful reentry. Figure 6 shows electrograms
from the basic paced His bundle beat at a cycle
length of 380 msec and the premature His bundle
beat that failed to initiate a circus movement at a
coupling interval of 250 msec. The insert portion of
Figures 6 and 7 represents the activation map of
the premature beat and the positions at which the
electrograms were recorded. The figure demonstrates conduction block between contiguous sites
11 and 19 and 12 and 20. Analysis of the electrogram
at site 19 during the basic paced His bundle beat
shows that it is a multiphasic deflection composed
of an initial small rs deflection that is simultaneous
with the most rapid deflection of the electrogram
at site 11. This is followed by a sharp r'S' deflection,
the maximum slope of which is approximately 10
msec later than that of electrogram 11. During the
premature beat only the initial deflection is recorded and the sharp terminal deflection fails to be
inscribed. This represents conduction block between sites 11 and 19. The initial small deflection
of electrogram 19 probably reflects distant activation at site 11, whereas the sharp late deflection
represents the moment the activation wave front
crosses the electrode site. During the premature
beat, site 19 is activated 110 msec later from the
slow activation front spreading from the opposite
direction. It records a sharp Rs deflection with a
polarity opposite to the sharp r'S' deflection of the
electrogram during the basic paced His bundle beat.
Figure 7 illustrates simultaneous electrograms
from the basic paced His bundle beat, the premature beat at a cycle length of 230 msec and the first
reentrant beat. Compared to Figure 6, in addition
to conduction block between sites 12 and 20 and
sites 11 and 19, there is also block between sites 11
and 10, 8 and 16, and 15 and 16. In Figure 6,
electrograms at sites 10 and 16 show only some
widening and fractionation during the premature
beat that did not result in reentry. This is consistent
with slowing of conduction. In Figure 7, these electrograms show evidence of conduction block and
reactivation from a delayed wave front as was described for site 19. Site 20, which initially shows
conduction block relative to site 12, is activated 180
msec later from the slow activation front moving
EPICARDIAL MAPPING OF REENTRANT CIRCUITS/El-Sherif and Smith
VI
259
FIGURE 6 Selected simultaneous electrograms from contiguous sites on the epicardial map
of the premature beat that failed
to initiate reentry (in Fig. 3,
panel A). The sites of recording
are indicated on the map.
Straight lines with double bars
indicate conduction block. See
text for details.
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from left to right along the lower border of the arc
of conduction block. Site 20 then reactivates site 12,
thus completing the reentrant circuit. Electrograms
31 to 35 illustrate sequential conduction delay along
the slow wavefront moving across the grid from left
to right. Conduction delay betwen sites 31 and 35 is
120 msec compared to 80 msec during the premature beat that failed to induce reentry in Figure 6.
Thus successful reentry is related both to the pres-
ence of a longer arc of conduction block and hence
a longer reentrant pathway, and to slower conduction along the pathway. Site 36 shows repetitive
conduction block (tachycardia-dependent) during
the reentrant ventricular tachycardia starting with
the premature beat. Site 35 also shows repetitive
block during the tachycardia starting with the first
reentrant beat.
Figure 8, panel A, illustrates the epicardial map
FIGURE 7 Selected simultaneous electrograms from contiguous sites on the epicardial map
of the premature beat that initiated a reentrant ventricular
tachycardia (in Fig. 3, panel B).
The sites of recording are indicated on the map. Conduction
block in indicated by straight
lines with double bars. The asterisk represents the site of early
reexcitation. Note sequential
conduction delay between sites
31 to 35 recorded across the
pathway of the slow activation
front. See text for more details.
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FIGURE 8 /I: Epicardial isochronal map of the second
reentrant beat in Figure 3, panel B. Activation times are
measured from the stimulus artifact of the His bundle
premature beat that initiated the tachycardia. B: Epicardial isochronal map of the last beat in Figure 3,
panel C. Activation times are measured in reference to
site 12 at the right upper corner of the grid. See text for
details.
of the second reentrant beat in Figure 3B and panel
B shows the epicardial map of the last reentrant
beat in Figure 3C. In panel A, the map shows a gap
in activation between 240 msec at the right upper
border of the grid and 290 msec. Although it is
likely that activation was taking place beyond the
upper border of the grid, there is no direct proof
that the second reentrant beat is a direct continuation of the first beat. However, the epicardial
activation pattern of the second reentrant beat is
similar to that of the first reentrant beat shown in
Figure 5, panel B, with the following differences
noted: (1) The length of the arc of conduction block
used for this and subsequent reentrant circuits is
VOL. 49, No. 1, JULY
1981
shorter (2.2 to 2.6 cm) compared to the one used
for the first reentrant circuit (3.6 cm). (2) The main
activation wavefront advancing from the left upper
corner of the grid spreads relatively rapidly to the
middle lower border of the grid where it blocks
before it collides with the also relatively fast spread
of the separate wave front moving from the lower
right corner of the grid. (3) The area of block
marked "x" extends to involve sites 35 and 36. (4)
The middle right border of the grid is now activated
10 msec after reactivation of site 12. By contrast,
during the first reentrant beat this site was activated before reexcitation of site 12. Analysis of
subsequent reentrant beats showed that the reentrant circuit during regular ventricular tachycardia
consisted of a continuous arc of conduction block
along the right upper border of the grid around
which the activation wave front circulated slowly
along its inferior border and much more rapidly
along its superior border. The rest of the epicardial
surface was activated by radial spread from the
circulating wave front except at the lower part of
the grid where conduction block confined the reentrant circuit.
Figure 8, panel B, illustrates the spontaneous
termination of the reentrant tachycardia. Figure 3,
panel C, shows that the last cycle of the tachycardia
is 10 msec shorter than preceding cycles. Activation
times are measured in reference to site 12 at the
right upper comer of the grid. The epicardial map
shows the occurrence of conduction block along
that part of the reentrant circuit showing the slowest conduction. The occurrence of conduction block
at this relatively narrow isthmus that during the
reentrant tachycardia was sandwiched between the
constant upper and lower arcs of conduction block
results in one large continuous arc of conduction
block across the grid. There is an attempt by the
separate wavefront from the lower right border to
spread upward past the area of conduction block
marked "x," but this little bulge of the activation
front also shows conduction block at the upper right
border of the grid.
By changing the coupling interval of the premature His bundle beat, ventricular tachycardia and/
or ectopic ventricular beats with different QRS
morphologies could be induced in all experiments.
Thirty-one different epicardial maps of either induced single ventricular beats or the first induced
beat in a run of pleomorphic ventricular rhythm
were analyzed. In addition, epicardial maps during
seven different runs of monomorphic ventricular
tachycardia (defined as six or more consecutive
beats) also were analyzed. In the first group, 7 out
of 31 maps (23%) obtained from six dogs revealed a
reentrant pathway that was mainly discernible on
the epicardial surface using the 3.6 x 4.6 cm electrode grid. In each map, the major part of the arc
of conduction block as well as the site of unidirectional block that showed early reexcitation could be
defined. On the other hand, in only one out of seven
EPICARDIAL MAPPING OF REENTRANT CIRCUITS/El-Sherif and Smith
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different runs of ventricular tachycardia (14%) was
the reentrant circuit displayed in the main on the
epicardial surface (see Fig. 8A). The length of the
epicardial reentrant pathway ranged from 3.6 to 9.6
cm. The time required to complete the circus movement was on the order of 160 to 260 msec. This
value was taken to reflect the refractory period of
the site of unidirectional block that showed early
reexcitation (Alessie et al., 1976; De Bakker et al.,
1979).
In 19 epicardial maps, a variable part of the arc
of conduction block and the circulating wavefront
around it could be mapped on the epicardial surface.
In these beats it could only be argued that a possible
reentrant circuit extended either on the epicardial
surface beyond the reach of the electrode grid or
deep to the immediate subepicardial layer of muscle. This is illustrated in Figure 9 which shows the
epicardial maps of the first two beats of a ventricular tachycardia (panels A and B, respectively)
initiated by premature His bundle stimulation. The
map under A shows two arcs of conduction block
and a wavefront moving from the lower to the upper
border of the grid and along the right border of the
longer arc of conduction block. A delayed wavefront
is seen moving in a downward and leftward direction along the left border of the arc of conduction
block. The map suggests the completion of a reentrant circuit in the sense that areas that showed
conduction block in response to the His bundle
261
premature beat were reactivated from what seems
to be a circulating wavefront. Electrograms 21 to 28
recorded across the epicardial grid from left to right
at the level of the horizontal arrows help to illustrate this point. Electrograms 21-23 show no discernible electrical activity (i.e., conduction block)
following the premature beat but are reactivated
during the first and subsequent beats of the tachycardia. However, the total circulating wavefront is
not discernible on the epicardial map. The time gap
between the two activation fronts moving in opposite directions may represent activation either on
the epicardial surface beyond the reach of the electrode grid or deep in the myocardium. On the other
hand, one cannot exclude an ectopic focus or a
reentrant circuit located in the subendocardium or
intramyocardial layers with an epicardial spread
showing areas of conduction block and multiple
slow wavefronts. The epicardial map of the second
beat of the tachycardia (panel B) shows a much
larger time gap between the circulating wavefront
along the right border of the arc of conduction block
and the area of reactivation at left upper corner of
the grid. In this beat, a reentrant mechanism is
even less certain. With the exception of the ventricular tachycardia shown in Figure 3, analysis of
epicardial maps in six other runs of regular ventricular tachycardia showed that the first beat of the
tachycardia had a larger part of a possible reentrant
circuit displayed on the epicardial surface. HOW-
FIGURE 9 Epicardial isochronal maps of the first two
beats of ventricular tachycardia induced by premature His
bundle stimulation (panels A
and B, respectively). The upper recording illustrates the
surface ECG (#1) and eight
simultaneous
electrograms
recorded across the epicardial grid from left to right
borders at the level of the horizontal arrows (electrograms
21 to 28, respectively). The
points for computer measurement of activation times are
shown as vertical lines. Activation times are measured
from the onset of the QRS of
the His bundle premature
beat (marked by a vertical arrow on the top tracing). The
maps are constructed at 20msec intervals. Note failure of
epicardial maps to depict a
complete reentrant circuit.
See text for details.
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ever, the second and subsequent beats seem to have
a larger intramyocardial and/or subendocardial extension (compare panels A and B in Figure 9).
In the 11 remaining epicardial maps that were
analyzed, areas of conduction block and/or slow
activation fronts could be identified. However, there
was no evidence that these areas constituted part
of a possible reentrant circuit. This was sometimes
seen even though the epicardial site for placement
of the grid was chosen because the composite electrogram from the same site displayed continuous
spikes throughout the diastolic interval. One such
example is shown in Figure 10 which was recorded
from another experiment. The figure illustrates the
epicardial map of a single ectopic beat induced by
premature His bundle stimulation. The composite
electrode recording (CE) at the bottom of the figure
shows continuous asynchronous spikes bridging the
diastolic interval between the His bundle premature
beat and the ventricular ectopic beat. The epicardial map shows rapid activation wavefronts that
invade the epicardium almost simultaneously at the
upper, right and left borders of the grid. The activation wavefronts converge toward the center of
the grid where conduction is blocked in all directions leaving an island of approximately 2.4 x 2.4
cm that is isolated totally from the surrounding
activation fronts. Within this island a separate activation wave breaks through some 60 msec later at
its right border and moves slowly in a left and
FIGURE 10 Epicardial isochronal map of a possible
reentrant beat induced by premature His bundle stimulation. The map illustrates a dissociated slow epicardial
wavefront unrelated to a reentrant circuit which may be
taking place deep to the immediate subepicardial layer
of muscle. The asterisks represent sites of early epicardial reexcitation. Note that a composite electrode recording (CE) from the same epicardial site shows continuous asynchronous spikes bridging the diastolic interval between the His bundle premature beat and the
ectopic beat.
VOL. 49, No. 1, JULY
1981
downward direction where it disappears. Reactivation of an area of the epicardial surface to the right
of the island takes place (marked by asterisks) while
the separate slow activation wave is still spreading
in the opposite direction. In this example it could
be argued that the major part of a possible reentrant
circuit occurred deep to the superficial layer of
myocardium. On the other hand, it is clear that
what the composite electrode has recorded as continuous electrical activity through the diastolic interval represents a separate dissociated slow wavefront on the epicardial surface that is unrelated to
the possible reentrant circuit.
Discussion
Technical Limitations of the Study
The present study provides a detailed analysis of
electrophysiological determinants of reentrant circuits in ischemic ventricular myocardium. However, the spread of excitation in ventricular myocardium is a three-dimensional process, and mapping of a limited area of the epicardial surface has
significant limitations. These limitations were minimized by mapping the reentrant circuits in a model
in which some of the circuits seem to be limited
largely to the epicardial surface. However, the number of reentrant beats for which most of the reentrant circuit could be identified on the epicardial
surface was small. Many reentrant circuits seem to
have a variable component of the circuit in some
deeper layer of myocardium. Even in the example
of reentrant tachycardia in Figure 3, certain assumptions have to be made to explain the spread of
excitation from endocardium to epicardium during
the His bundle premature beat that initiated reentry. In this example, activation of the epicardial
surface at the upper border of the arc of conduction
block occurred almost simultaneously 10-20 msec
after the inscription of the QRS complex in the
surface ECG. This suggests that activation spreads
in broad wavefronts from endo to epicardium, possibly in a tangential fashion. The successful completion of the slow epicardial activation front along
the other side of the arc of conduction block requires that direct endo-to-epicardial breakthrough
along the pathway does not take place. Thus, the
assumption has to be made that endo-to-epicardial
activation along a broad segment of the lower border of the reentrant circuit is either much slower
than the epicardial wavefront or is blocked totally.
This and similar other assumptions could be verified only by obtaining endocardial and intramyocardial recordings. Because of the absence of such
recordings in the present study, an unequivocal
proof of a reentrant mechanism could not be made.
As mentioned earlier in conjunction with Figure 9,
the possibility of an automatic focus or a separate
reentrant circuit in the subendocardial or intramyocardial layers cannot be excluded. However, in at
least eight different epicardial maps, there was a
strong suggestion of a reentrant mechanism.
EPICARDIAL MAPPING OF REENTRANT CIRCUITS/El-Sherif and Smith
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The relatively small size of the epicardial grid
presents a limitation to mapping of the overall
epicardial spread of reentrant circuits. Also, the
relatively wide spacing of the close bipolar points
(5-6 mm apart) may limit accurate mapping of slow
activation fronts.
Several recent mapping studies have used either
close bipolar (De Bakker et al., 1979) or unipolar
electrodes (Allessie et al., 1977; Janse et al., 1980).
In a bipolar signal there are at least two moments
of activation, one for each terminal. When interelectrode distance is small, conduction velocity is
high, and the activation front proceeds regularly at
right angles to the electrode axis, the electrode will
record an electrogram with a rapid intrinsic deflection, and the activation time of the midpoint between the two terminals can be identified easily. On
the other hand, in the presence of a very slow and
irregular activation front and a relatively large interelectrode distance, a broad multiphasic electrogram may be recorded and the moment of activation at the midpoint between the two terminals
may not be accurately identified. However, it
should be stressed that, in the presence of a very
slow and irregular wavefront, a unipolar electrode
may also record a broad multiphasic deflection in
which the moment of activation is less well defined
(Janse et al., 1980). Further, in a bipolar recording,
there is the theoretical possibility that, in cases
where the activation front is directed perpendicular
to the line connecting the two terminals, no deflection will be recorded and one could erroneously
conclude that conduction block is present. However, the present study suggests that if temporal
relationships between contiguous sites are taken
into consideration, possible slight inaccuracies in
the identification of the moment of activation at
one or more sites may not significantly interfere
with satisfactory mapping of activation fronts. This
view has also been emphasized recently in mapping
studies that used unipolar recordings (Janse et al.,
1980).
The present study, also has demonstrated some
of the limitations of composite electrode recordings
which cannot discern the presence of zones of unidirectional block. Further, because of the marked
degree of heterogeneous conduction in the infarction zone, a composite electrode recording is unable
to discern whether continuous electrical activity in
diastole reflects the slow activation front of an
epicardially located reentrant pathway or a slow
dissociated wavefront unrelated to the reentrant
circuit.
Electrophysiological Determinants of
Reentrant Circuits in Ischemic Ventricular
Myocardium
Reentrant circuits are generally governed by
three factors which are themselves closely interdependent. These are (Lewis, 1925): (1) the length of
the myocardial pathway, (2) the rate of conduction
263
of the activation wave, and (3) the duration of
refractoriness along the circular pathway. For example, in the presence of a relatively slow conduction and short refractoriness, a successful reentrant
circuit may require only a short pathway. The
present study suggests that both the length of the
arc of conduction block which defines the length of
the reentrant pathway and the degree of slow conduction are crucial factors for the creation of a
reentrant circuit. A premature beat that successfully initiates reentry results in a longer arc of
conduction block and slower conduction compared
to one that fails to induce reentry (see Fig. 5). The
slower activation wave travels around a longer,
more circuitous route, thus providing enough time
for refractoriness along the aide of unidirectional
block to expire at one point. Reexcitation of this
site will complete the reentrant circuit. Refractory
periods at sites of reexcitation varied from 160 to
260 msec in the present study. These figures are
consistent with normal to moderately prolonged
refractory periods in canine ventricular myocardium (Janse et al., 1969) and are different from the
very short refractory periods in a study of reentrant
circuits in canine right ventricle (De Bakker et al.,
1979).
The present study has emphasized the functional
nature of the obstacle (the arc of conduction block)
around which a reentrant circuit is formed. This is
illustrated by the fact that, in the same area of the
myocardium, activation can proceed at a relatively
fast speed during relatively slow heart rates. This
means that both the zone of conduction block and
the slow conduction around it are created by areas
of myocardium with abnormally prolonged refractoriness when these areas are challenged to conduct
at cycle lengths shorter than the time necessary for
full recovery of excitability. As was shown in other
studies using the same canine model, ischemia does
in fact result in abnormal lengthening of refractoriness of myocardial cells that usually extends beyond the completion of the action potential [postrepolarization refractoriness (El-Sherif and Lazzara, 1979)]. Although in the present study conduction block and slow conduction necessary for reentry were created by premature beats during a relatively slow constant pacing rate, it should be emphasized that, in the same experimental model,
reentrant circuits could also occur during regular
cardiac rhythm even at slow rates (El-Sherif et al.,
1977a, 1977b). Thus a basic formula for reentry
depends on the degree of lengthening of refractoriness at a particular myocardial site relative to the
preceding cardiac cycle length. At this site,
shorter—but not necessarily short—cycle lengths
could result in slow conduction and/or conduction
block. Only a slight shortening of the preceding
cycle length on the order of 10-20 msec may induce
marked slowing of conduction and/or block in an
area that was previously conducting at a relatively
fast rate.
264
CIRCULATION RESEARCH
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The functional nature of the obstacle around
which a ventricular reentrant circuit is formed is
very similar to that which has been demonstrated
during reentry in small pieces of rabbit atrial myocardium (Allessie et al, 1977). This type of reentry
is clearly different from the one that requires a
preformed anatomical obstacle, as originally described by Lewis et al. (1918-1921) in atrial flutter.
The difference in electrophysiological characteristics of the reentrant circuit between the two types
of reentry was discussed extensively by Allessie et
al. (1977). It should be stressed that the scar of a
myocardial infarction could be considered as a fixed
anatomic obstacle and that some reentrant circuits
could have their arc of conduction block made
partly of a myocardial scar and partly of areas with
functional block. However, the role of fixed conduction block in the myocardial scar could not be
analyzed in detail in the present study because of
lack of intramyocardial recordings and of anatomicelectrophysiological correlative studies. Further,
since recordings were not routinely obtained at
widely varying cardiac cycle lengths (particularly
very long cycle lengths), it was difficult to differentiate rate-related functional conduction block
from non-rate-related fixed block.
During a continuously circulating wavefront, the
zone of conduction block at the center of the reentrant circuit consists of excitable tissue that has
been rendered inexcitable. This was explained in
the model of reentry in small pieces of rabbit atrial
myocardium by the invasion and collision at the
center by multiple centripetal waves arising from
the leading reentrant circle (Allessie et al., 1977). A
slightly different explanation assumes that the
membrane potential of the fibers at the center is
held above threshold by the electrotonic influence
of the depolarization front which continuously turns
around this area (Allessie et al., 1973). In other
words, the central zone of conduction block consists
of an area of tachycardia-dependent paroxysmal
block. Tachycardia-dependent paroxysmal block
could be demonstrated at other sites of the epicardium that are not necessarily involved in a reentrant circuit (sites 35 and 36 during the reentrant
tachycardia shown in Figure 8). Tachycardia-dependent paroxysmal block has been demonstrated
previously in ischemic cardiac cells and takes the
form of repetitive small nonregenerative responses
when the cell is stimulated at relatively short cycle
lengths (El-Sherif et al., 1975).
The creation of a relatively large zone of conduction block requires the presence of abnormally prolonged refractoriness in a large confluent area of
the myocardium surrounded by zones of shorter
refractoriness. Since a 10-20 msec difference in the
preceding cycle length may be all that is required
to create conduction block, it is clear that the
dimension of a zone of prolonged refractoriness is
much more crucial than the degree of dispersion of
VOL. 49, No. 1, JULY
1981
refractoriness between contiguous zones. The impact of this observation on the feasibility of a reentrant arrhythmia following myocardial ischemic injury is obvious. It is reasonable to suggest that the
type of ischemic injury that results in one or a few
large confluent areas of abnormally prolonged refractoriness is more likely to create a fertile soil for
the initiation and maintenance of reentrant circuits.
In contrast, ischemic injury that results in a larger
number of small patchy islands of abnormal refractoriness amidst a sea of relatively normal refractoriness will be less conducive to reentry. Further, as
already pointed out by Allessie et al. (1976), it is
questionable that the measurement of the differences between shortest and longest refractory periods [so-called dispersion of refractoriness (Han
and Moe, 1964)] will be the decisive indicator of the
risk of development of reentrant arrhythmias compared to the spatial distribution of these differences.
In summary, the present study has presented
strong evidence to suggest ventricular reentrant
activation in the late myocardial infarction period
and has analyzed some electrophysiological characteristics of the reentrant circuit. On the other
hand, the study has emphasized the limitations of
epicardial mapping and the need for multiple subendocardial and intramyocardial recordings before
reentrant activation can be established unequivocally in the present canine model.
Acknowledgments
We wish to acknowledge Theresa Luppowitz for preparation
of the manuscript and Mike Yu and Charles Mills for the art
work. We are grateful to Dr. J J V Abildskov for encouragement
and advice.
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Modulation of Atrioventricular Conduction
by Isometric Exercise in Human Subjects
ALBERTO FERRARI, OSCAR BONAZZI, MARIA GARDUMI, LUISA GREGORINI,
RODOLFO PERONDI, AND GlUSEPPE MANCIA
SUMMARY In humans, arterial baroreceptorg depress atrioventricular (AV) conduction through
vagal influences on the AV node but not on the His-Purkinje fibers. We investigated the influence on
AV conduction of an excitatory neural influence, i.e., isometric exercise (handgrip). In subjects with
normal AV conduction, blood pressure was measured by an intra-arterial catheter, R-R interval by an
electrocardiogram, and A-H and H-V intervals (representing conduction, respectively, through the AV
node and the His-Purkinje fibers) by His bundle recording. Handgrip raised blood pressure markedly,
it shortened R-R interval, and caused no change in A-H and H-V intervals. Because prior studies had
demonstrated that autonomic influences over AV conduction can be quantified accurately only when
heart rate is constant, the subjects also were studied during atrial pacing. Under this condition,
handgrip again caused a marked pressor response but also induced a marked shortening in the A-H
interval (30%) whereas the H-V interval still wax unaffected. The handgrip-induced shortening in the
A-H Interval was less pronounced after atropine but it was also Impaired by propranolol. Thus AV
conduction normally is modulated by inhibitory influences but also by powerful excitatory stimuli. Like
the inhibitory influences, the excitatory ones are seen mainly at constant heart rate and are limited to
the AV node with no effect on the His-Purkinje fibers. Unlike the Inhibitory influences, however, the
excitatory modulation is substantially mediated via the cardiac sympathetic nerves. Circ Res 49: 265271, 1981
SEVERAL studies suggest that the autonomic
nerves may have a large influence on atrioventricular conduction. First, a considerable number of
vflgal and sympathetic fibers impinge upon this
structure along its entire course (Cohn and Lewis,
1913; Morison, 1912; Geis et al, 1973; Levy and
Martin, 1979). Second, when electrical stimulation
From the IstiUiti di Ricerche CordiovascoUri, Clinics Medica II and
Patologia Medica I, Univerata di Milano, Centre di Ricerche Cirdiovwcolari del CNR, Milano, Italy
Addreaa for reprint*. Profesaor Giuseppe Majicia, Ljuuito Riceiche
Cardiovascolan, Polidinico, Via F. Sforza 35, 20122 Milano, Italy.
Received September 26, 1980; accepted for publication January 27,
1981.
of the cardiac branches of the vagus is performed in
animals, there can be a marked depression of atrioventricular conduction (Levy and Zieske, 1969;
Martin, 1977; West and Toda, 1967). Third, when
the electrical stimulus is applied to the cardiac
sympathetic branches, atrioventricular conduction
can, conversely, be markedly accelerated (Gesell,
1916; Wallace and Sarnoff, 1964; Levy and Zieske,
1969; Priola, 1973; Spear and Moore, 1973).
However, the above-mentioned studies only indicate a large potential ability of the vagal and
sympathetic nerves to influence atrioventricular
conduction and do not provide evidence concerning
whether and to what extent this ability is used
Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial
mapping of reentrant circuits.
N El-Sherif, R A Smith and K Evans
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Circ Res. 1981;49:255-265
doi: 10.1161/01.RES.49.1.255
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Copyright © 1981 American Heart Association, Inc. All rights reserved.
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