(Circulation. 1995;91:2378-2384.)
© 1995 American Heart Association, Inc.
Articles |
Relation Between Repolarization and Refractoriness During Programmed Electrical Stimulation in the Human Right Ventricle
Implications for Ventricular Tachycardia Induction
From the Veterans Administration Medical Center and Georgetown University Cardiology Divisions, Washington, DC.
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Abstract |
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Background Although programmed electrical stimulation is widely used for provoking sustained ventricular tachycardia (VT), the mechanism by which repetitive extrastimulation evokes VT is still little understood. Specifically, it is not clear why several closely coupled extrastimuli are frequently required to induce VT. Although regularly paced human ventricular myocardium exhibits a near constant relation between myocardial repolarization and refractoriness, the effect of repetitive extrastimulation on the relation between repolarization and excitability in the human heart and its relevance for arrhythmia induction by programmed stimulation are unknown. We hypothesized that the induction of VT by repetitive extrastimulation is facilitated by an altered relation between repolarization and refractoriness, and this leads to disturbances in ventricular impulse propagation, which trigger the onset of VT.
Methods and Results Twenty-one patients undergoing routine electrophysiological study were paced from the right ventricular apex and outflow tract endocardium with monophasic action potential–pacing catheters placed at both sites simultaneously. Monophasic action potential durations (APDs) and effective refractory periods (ERPs) were measured simultaneously at each site, during regular stimulation (S1-S1) at 400-ms cycle length and during three consecutive extrastimuli (S2 through S4) at the closest coupling intervals at which all three extrastimuli still resulted in capture. Measurements further included the repolarization level at which the earliest capture occurred, the ratio between ERP and APD, and the propagation time between the pacing and distant recording site. APD and ERP both shortened progressively with each extrastimulus. APD at 90% repolarization decreased from a baseline (S1) of 238.1±19.7 ms by 14.9% at S2, 18.9% at S3, and 22.9% at S4 (P<.0001, S1 versus S4). ERP decreased from 233.1±19.7 ms (S1) to 180.0±41.9 ms (S3) (P<.0001, S1 versus S3). While ERP shortening occurred mainly on the basis of APD shortening, there was an additional factor that contributed to ERP shortening independent of APD shortening. Each consecutive extrastimulus was able to elicit a propagated response at earlier repolarization levels than the previous one: the earliest capture for S2 occurred at 85.5±10.2% of complete repolarization, for S3 at 83.9±10.5%, and for S4 at 78.4±11.2% (P<.05 for S2 versus S3; P<.05 for S3 versus S4; P<.01 for S2 versus S4). This progressive "encroachment" of the earliest capture stimulus onto the preceding repolarization phase (at progressively less repolarized levels) correlated with a progressive delay of impulse propagation between the pacing site and the second recording site: propagation time increased from baseline (S1) by 10.5±1.3% with S2 to 19.0±1.6% with S3 and to 22.5±2.8% with S4 (P<.05, S4 versus S1). VT was induced in 11 of 21 patients. Nine of these had VT induced only when significant encroachment of extrastimuli on the preceding repolarization phase (<81.3±7.0%) and associated conduction slowing (>16.6±1.8%) were present.
Conclusions Repetitive extrastimulation not only shortens APD and subsequently ERP but also alters the ERP/APD relation by allowing capture to occur at progressively less complete repolarization levels. This progressive encroachment onto the preceding repolarization phase is associated with impaired impulse propagation and a high incidence of VT induction. This may help explain how repetitive, closely coupled extrastimulation induces ventricular tachycardia in the human heart.
Key Words: electric stimulation • tachycardia • action potentials • catheters
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Introduction |
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Programmed electrical stimulation of the right ventricle is widely used to provoke sustained ventricular tachycardia (VT) in patients who have had clinical events of VT, syncope, or sudden cardiac death. Although there is a large body of evidence relating clinically documented VT to artificially provoked ventricular arrhythmias,1 2 3 4 5 the mechanism by which repetitive right ventricular (RV) extrastimulation evokes such arrhythmias is still poorly understood. Specifically, it is not clear why programmed electrical stimulation must often reach a certain level of "aggressiveness" to induce sustained VT. It is empirically known but not yet scientifically explained that the probability of inducing VT in a patient increases with the number of electrical extrastimuli and with the closeness with which each consecutive extrastimulus is delivered to the myocardium.
During regular pacing there is a close relation between the duration of the action potential (APD) and the effective refractory period (ERP) or, in other terms, between the level of repolarization and the return of excitability. In both animal6 7 8 9 and human ventricular myocardium,10 excitability recurs at a repolarization level of approximately 85%, and this relation is constant over a wide range of steady-state cycle lengths.8 10 Little is known, however, of the effect of repetitive extrastimulation on the relation between repolarization and excitability in the human heart. It has been suggested that repetitive extrastimulation decreases the APD and thereby the coupling interval to capture the myocardium,11 resulting in the greater inducibility of VT with repetitive extrastimulation.1 12 However, shortening of the APD or the ERP does not increase the susceptibility for reentrant tachycardia. For instance, sinus tachycardia, with its associated rate-dependent shortening of APD and ERP, is not a common cause of ventricular arrhythmias. Thus, additional mechanisms must facilitate VT induction by repetitive extrastimulation.
We hypothesized that the induction of VT by repetitive extrastimuli is facilitated by an altered relation between repolarization and refractoriness, and this leads to disturbances in ventricular impulse propagation, which trigger the onset of VT. The specific objectives of this study were (1) to determine the effects of repetitive closely coupled extrastimuli on the instantaneous relation between repolarization and excitability at two RV sites, (2) to assess the effects of an altered repolarization-excitability ratio on impulse propagation between the two RV sites, and (3) to assess the significance of such alterations for the inducibility of VT by programmed electrical stimulation.
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Methods |
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Patients
The study was performed in 21 male patients 47 to 78 years old (mean, 58±6 years) who underwent electrophysiological testing for documented or clinically suspected VT. The underlying heart diseases were coronary artery disease (16 patients) and idiopathic dilated cardiomyopathy (5 patients). The mean left ventricular (LV) ejection fraction was 34.5% (range, 11% to 55%).
Electrophysiological Study
Electrophysiological studies were
performed in the baseline
state, with antiarrhythmic drugs withdrawn for at least 5 half-lives.
All patients gave informed written consent to a protocol that had been
approved by the institutional review board on human investigation. Two
monophasic action potential (MAP)-pacing combination catheters were
positioned in the RV, one in the apex and one in the outflow tract.
Pacing was performed with a 2-ms pulse duration at precisely twice
diastolic threshold strength with a programmable electrical stimulator
(Bloom and Associates) and a custom-made constant-current isolation
unit (EP Technologies) that allowed fine-tuning of stimulus output
strength in the range <1 mA. The two MAPs and a six-lead surface ECG
were recorded on a multichannel recorder (Midas System 5000, PPG) at a
paper speed of 100 mm/s and also stored digitally on a BARD
electrophysiology recording system.
Simultaneous Determination of APD and ERP
The technique for
simultaneous determination of APD and ERP via
the MAP-pacing combination catheter has been detailed
earlier.9 13 Briefly, MAP recordings were obtained
with
two nonpolarizable silver–silver chloride electrodes, one at the tip
of the catheter and the other located 5 mm proximal to the tip. Pacing
was performed with two platinum electrodes mounted opposite each other
at a 2-mm distance from the catheter tip. Because of the close spacing
between the pacing dipole and the MAP recording electrode, the APD and
the ERP could be measured at nearly identical myocardial sites. This
helped avoid correlation errors that might result from the variability
of both APD and ERP among separate ventricular
sites.14 15
In addition, the short distance between recording and pacing electrodes
results in minimal conduction delays between the pacing and recording
site, as evident from the fact that the stimulus artifact
coincides with the upstroke of the MAP (Fig 1
).
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In all patients, pacing was performed from the RV apex and outflow tract; the pacing sequences were randomized. The hearts were paced at a basic (S1-S1) cycle length of 400 ms. After every eighth S1, an extrastimulus (S2) was introduced during early electrical diastole after the S1 response. The S1-S2 coupling interval was decreased in steps of 10 ms until the extrastimulus began to encroach onto the repolarization phase of the S1 response. At this point, the coupling interval was decreased in 5-ms steps until capture no longer occurred. The longest coupling interval between the basic (S1) MAP upstroke and the extrastimulus (S2) artifact that failed to produce a ventricular response was defined as the ERP. Next, the S1-S2 coupling interval was lengthened by 50 ms, and a second extrastimulus (S3) was introduced at a 50-ms delay from the preceding S2 response repolarization. Both the S1-S2 and the S2-S3 coupling intervals were then decreased until the shortest intervals that still resulted in capture were determined. This was verified by a 5-ms decrement resulting in refractoriness. Finally, a third extrastimulus (S4) was added, and the above procedure was repeated. Each eight-beat drive train and extrastimulus sequence was interrupted by a 2-second pause. This pacing protocol closely followed the routine procedure of electrophysiological testing. This was intended to make our arrhythmia inducibility data comparable to the existing literature.
Data Analysis
The following variables were analyzed during
the closest
S1-to-S4 stimulation sequence: (1) APD at the level of 90%
repolarization (APD90)10 at the stimulation
site and at the distant recording site (RV apex and outflow tract); (2)
the ERP for S1, S2, and S3; (3) the repolarization level at which each
extrastimulus (S2, S3, S4) captured with the closest possible coupling
interval (the basic MAP served as the reference); and (4) the
propagation time between the two pacing/recording sites (either RV apex
to outflow tract or vice versa). This was determined as the interval
between the upstrokes of the two MAPs. Sustained VT was defined as
inducible when it lasted for at least 15 seconds. VT inducibility was
related both to the degree of incomplete repolarization levels at which
extrastimuli produced propagated responses and to the increase in
propagation time between the RV pacing and distant RV recording
site.
Statistical Analysis
Data are presented as mean±SD.
One-way ANOVA was used to
estimate the significance of differences for APD, ERP, closest
repolarization capture level, and propagation time between the two
pacing/recording sites during basic S1 stimulation and S2 through S4
extrastimulation. A value of P<.05 was considered
significant. The statistical analyses were done with JMP
software from SAS Institute, Cary, NC.
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Results |
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Both MAP-pacing combination catheters maintained a stable position in the RV apex and outflow tract, respectively, during the entire study protocol. The MAP signals had initial amplitudes ranging from 12 to 35 mV (mean, 15±9 mV). A 15% to 25% loss in amplitude was seen over the course of the study protocol. Despite this decline in amplitude, the MAP signals retained a smooth configuration with sharp upstrokes, a convex plateau phase and final repolarization phase, and flat diastolic intervals, known to be hallmarks of high-fidelity MAP recordings.13 The diastolic pacing thresholds averaged 0.12±0.05 mA at both sites in all patients and, although frequently interrogated, rarely required adjustment.
APD90 and ERP Changes During Maximally Close Repetitive
Extrastimulation
There was a cumulative shortening of both
APD90 and
ERP with each extrastimulus. The APD90 and ERP shortening
was observed at both the pacing site and the distant recording site. At
the pacing site, APD90 was 238.1±19.7 ms at S1 and
decreased 14.9% at S2, 18.9% at S3, and 22.9% at S4 extrastimulation
(P<.0001, S1 versus S4). At the distant recording site,
APD90 was 228.7±24.1 ms at S1 and shortened 7.4% at S2,
15.7% at S3, and 17.9% at S4 (P<.0001, S1 versus S4) (Fig
2). The ERP shortened from 233.1±19.7 ms at S1 to
180.0±41.9 ms at S3 (P<.0001, S1 versus S3) (Fig
3). Because only three extrastimuli were introduced, the
ERP associated with the last (S4) action potential could not be
determined.
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Relation Between APD and ERP During Repetitive
Extrastimulation
The MAP recordings demonstrated that the shortening
of the ERP
during repetitive extrastimulation was due to two mechanisms: the first
was the progressive decrease (up to 22.9%) of the APD during
repetitive extrastimulation. Second, repetitive extrastimulation
decreased the ratio between the ERP and the APD progressively. As shown
in Fig 1
, the repolarization level at which premature
extrastimulation
of twice diastolic threshold strength produced the earliest propagated
response ("takeoff" potential) shifted upward, to less complete
repolarization levels, with each additional extrastimulus. Earliest
capture for S2 was possible when the preceding action potential was
repolarized to a level of 85.5±10.2%; earliest capture for S3
occurred at 83.9±10.3% of the preceding repolarization phase
(P<.05, S2 versus S3) and for S4 at a repolarization level
of 78.4±11.2% (P<.05, S3 versus S4; P<.01, S2
versus S4) (Fig 4). Thus, each additional extrastimulus
that still captured the myocardium could do so at progressively less
complete repolarization levels.
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Propagation Time During Repetitive Extrastimulation
The
propagation time from the upstroke of the directly paced MAP
response to the distantly recorded MAP upstroke was constant during
regular pacing as well as during extrastimulation, so long as
extrastimuli were applied after complete repolarization. As
extrastimuli began to encroach upon the repolarization phase of the
preceding action potential, propagation time between the pacing site
and the distant recording site increased. This prolongation in
propagation time increased with the degree by which each additional
capturing extrastimulus was able to further encroach onto the preceding
repolarization phase. Compared with baseline S1-S1 pacing, propagation
time between the pacing site increased by 10.5±1.3% with the closest
S2, by 19.0±1.6% with the closest S3, and by 22.5±2.8% with the
closest S4 (P<.05, S1 versus S4) (Fig 5).
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Induction of VT
Sustained VT was induced in 11 of 21 patients
(52.4%). The VT was
monomorphic in 8 of 11 patients (72.7%) and polymorphic in 3 of 11
patients (27.3%). In all but 2 patients with monomorphic VT, the VT
was induced only when extrastimuli encroached onto the preceding
repolarization phase at levels of <90%. All polymorphic VT followed
significant encroachment of the extrastimuli. There were no significant
differences in the APD90, the ERP, the ERP/APD
ratio, and the propagation time between the monomorphic and polymorphic
VTs. All patients who had encroachment of extrastimuli and VT
inducibility required more than 1 extrastimulus for VT induction; 2
patients were inducible with 2 extrastimuli, and 7 patients were
inducible only when 3 extrastimuli were introduced (Fig 6). At
the VT induction drive, S2 encroached onto
85.9±9.5% of the preceding repolarization phase, S3 onto
81.3±8.0%,
and S4 onto 79.6±6.4%. The encroaching extrastimulation was
associated with slowing of impulse conduction by 9.4±1.5% with S2 to
16.6±1.8% with S3 and to 29.4±1.6% with S4 preceding VT
induction.
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Discussion |
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There were several major findings in this prospective study. First, during repetitive extrastimulation, both APD and ERP shortened progressively with each additional extrastimulus. Second, each additional extrastimulus was able to capture the myocardium earlier during repolarization than the preceding extrastimulus. Third, this progressive encroachment of successive extrastimuli onto the preceding action potential's repolarization phase was associated with a slowing of impulse propagation from the paced to a distant recording site. Finally, VT occurred in 82% of inducible patients only when extrastimuli encroached onto the preceding repolarization phase.
Recording and Stimulation Technique
The effect of repetitive,
closely coupled extrastimuli on the
relation between local repolarization and refractoriness has not been
studied systematically in the human heart. Standard
electrophysiological catheter techniques depict unipolar or bipolar
differential electrograms, which identify local capture but not the
true time course of local myocardial repolarization. In this study, we
used a MAP-pacing combination catheter9 that allowed us to
record MAPs in the immediate vicinity of the pacing site and thereby
analyze simultaneously the instantaneous relation between the local
repolarization time course and the recurrence of excitability in the
human heart. In addition, the activation times at two different
ventricular sites were readily determined by the sharp upstrokes of the
MAPs at either site (uncluttered by pacing artifacts), and thus the
propagation time between the two sites could be determined with greater
accuracy than with standard electrode
catheters.13 16 17
Relation of APD to Extrastimulus Cycle Length
The shortening
of the APD90 correlated closely
(r=.80) with the decrease of the coupling interval during
repetitive extrastimulation. Although no comparable data during
repetitive extrastimulation exist, a close relation between the APD and
the preceding cycle length is well established for steady-state
pacing18 19 20 and during single
extrastimulation with
decreasing coupling intervals.11 21 22
The successive APD
shortening during maximally close repetitive stimulation can be
explained by two mechanisms: First, a closely coupled extrastimulus
decreases the subsequent APD, which in turn allows the next
extrastimulus to capture with a shorter coupling interval, which in
turn causes further APD shortening, and so forth. Second, the
progressive encroachment of earliest capture onto the preceding
repolarization phase during repetitive extrastimulation additionally
decreases the coupling interval and shortens the APD.
ERP/APD Ratio and Encroachment of Reexcitability
As described
in detail previously,8 9 10 the
single-site recording and pacing method demonstrates a close
correlation between APD and ERP. We showed in a previous
canine8 and human9 10 heart study that
at a
given site, the ERP/APD ratio during steady-state pacing is constant
and independent of the cycle length; refractoriness for a single
extrastimulus (S2) at twice diastolic threshold ceased and excitability
recurred at a repolarization level of 82±5% regardless of the prior
pacing cycle length.6 7 This correlation is
comparable to
in vitro findings in single cells.1 2 The present
human heart study corroborates these findings by confirming that a
single S2 extrastimulus was able to capture the local myocardium when
the preceding response had repolarized to, on average, 85.5%.
This relatively fixed relation between repolarization and refractoriness during regular pacing changed during closely coupled repetitive extrastimulation. With each additional extrastimulus, earliest capture occurred at progressively less complete repolarization levels. Neither experimental animal nor clinical human studies have yet reported that successive, maximally close extrastimuli are able to capture the myocardium at progressively earlier repolarization levels. Basic investigators, measuring transmembrane action potentials in excised myocardial tissue preparations, had little reason to apply programmed repetitive extrastimulation, whose purpose is to induce sustained ventricular arrhythmias. In the clinical arena, standard electrode catheters do not provide direct images of the local myocardial repolarization time course and therefore cannot be used to identify the direct relation between repolarization and excitability in the human heart.
Because of this lack of directly applicable basic or clinical data on the effects of repetitive, closely coupled extrastimulation, an explanation for the progressively earlier capture takeoff level must remain speculative at the present time. We propose two hypothetical explanations. (1) Myocardial responsiveness to premature electrical stimuli is governed by both voltage- and time-dependent recovery processes from inactivation of sodium channel conductance after a prior myocardial response.23 24 The earlier repolarization level at which each additional extrastimulus captures the myocardium could be due to an as yet undescribed phenomenon of "facilitation" that allows for earlier recovery of a subgroup of sodium channels during the course of repolarization when stimulated repetitively at close coupling intervals. This could be verified by intracellular action potential recordings in isolated cardiac cells during repetitive stimulation. (2) The phenomenon of progressive encroachment of repetitive extrastimuli could also be interpreted as a tissue phenomenon. Unlike single-cell, intracellular action potential recordings, the MAP catheter is known to simultaneously record the electrical activity from a multitude of cells in close proximity to the recording electrode.13 16 It is conceivable that the repolarization time courses of neighboring cells (and of their associated refractoriness) do not exactly coincide and that dispersion of repolarization and refractoriness in this cell population increases with each additional extrastimulus. A progressive divergence in electrical restitution curves with repetitive extrastimulation recently has been demonstrated for canine ventricular muscle fibers.25 If repolarization in the cell group underneath the MAP recording and stimulating electrode is dispersed in time and space, some cells may be captured early while others are still refractory. The discordance between the responsiveness of individual cells and the average (recorded) repolarization level may increase with repetitive extrastimulation. This would displace the average capture level to earlier repolarization.
Conduction Delay During Repetitive Close Extrastimulation
Regardless of whether the "facilitation of excitability"
phenomenon is based on single-channel dynamics or tissue properties, a
dyssynergy of cellular activation is bound to diminish the electrical
energy of the wave front and subsequently to reduce the initial
propagation velocity of the cardiac impulse.26 27 In
keeping with this hypothesis, the propagation time of the electrical
impulse between the stimulation and the recording site increased with
the first, closely coupled premature extrastimulus (S2) compared with
stimulation at the basic cycle length (S1-S1). Each additional closely
coupled extrastimulus (S3, S4) created further conduction delay of the
electrical impulse. This is in accordance with previous experimental
data that showed marked slowing of myocardial conduction properties
during incomplete repolarization or at more depolarized transmembrane
potentials.28 29
Impact of Encroachment and Conduction Slowing on VT
Inducibility
VT was induced in 82% of inducible patients only when the
repetitive extrastimuli captured the myocardium before 90% of the
preceding repolarization phase. In all cases, this was associated with
a delay in impulse conduction between the RV pacing and distant RV
recording sites. Several explanations might be hypothesized.
Encroachment of an electrical impulse onto the preceding repolarization
phase would encounter only a minority of sodium channels available for
activation and thus result in slowed impulse propagation through the
myocardium. Slowed conduction of the propagating electrical impulse is
associated with an increased probability of VT induction by two
mechanisms. First, slowing of conduction augments the dispersion of
activation times in the ventricles, which may increase the probability
that the electrical wave front initiates the reentry circuit during its
excitable gap. Second, progressive conduction slowing of the electrical
impulse results in an increased dispersion of the diastolic interval
between the stimulation site and recording sites, with longer diastolic
intervals at sites distant from the stimulation site.30
The increased range of diastolic intervals increases the dispersion of
ventricular repolarization (APD).30 31 Our clinical
data
support these experimental findings. Shortening of APD90
during repetitive, encroaching extrastimulation was more pronounced at
the electrically paced site (55 ms from S1 to S4) compared with
simultaneous APD90 shortening at the distant recording site
(42 ms, P<.05), which was activated by impulse propagation
with delayed conduction and increased diastolic intervals. The
different electrophysiological effects of encroaching extrastimulation
might also explain that we could induce both monomorphic and
polymorphic VT with repetitive closely coupled extrastimulation. The
explanations provided for VT induction account for a high percentage
(82%) of VT in our patients. In the remaining 18% of VTs that were
inducible without encroachment on repolarization, other
electrophysiological mechanisms may have prevailed.
Limitations
MAPs were of different magnitudes at different
endocardial sites
or in different patients and exhibited a gradual decline in amplitude
over the course of the study. However, this is of little concern for
the purpose of our study, which was not aimed at measuring the true
transmembrane potential but rather at depicting the proportions between
the relative time course of repolarization and its relation to
reexcitability. MAPs have been validated to provide this
information.16 The gradual decrease in MAP amplitude that
occurred without significant loss in MAP morphology is most likely due
to a decline in electrode contact pressure over
time.13
We collected our data from only two pacing and recording sites, both located at the RV endocardium. Therefore, we cannot predict the effects of repetitive RV extrastimulation on impulse propagation toward and within the LV myocardium and on the reentry substrate, which is most commonly located in the LV myocardium. The pathway within the RV is shorter than that anticipated for impulse propagation between an RV pacing site and an LV recording site. Both from a geometrical point of view and by considering the probable lack of myocardial disease in the RV, the conduction delay measured between two RV sites is likely to have underestimated the conduction delay from the RV to the LV myocardium. The fact that we found a significant prolongation in propagation time from one RV site to another corroborates rather than defeats our hypothesis that closely coupled extrastimuli are able to prolong impulse propagation within the myocardium.
Although our approach could not deliver local information about electrophysiological variables in the LV, we adhered to an RV pacing protocol because this is the one generally used in electrophysiological testing. We feel that information derived from this approach is most readily comparable to the published clinical database concerning VT induction by programmed electrical stimulation.
Conclusions
Using a catheter technique that allows
simultaneous pacing and
recording of MAPs in the human heart, we found that closely coupled
repetitive extrastimuli progressively shortened the local
repolarization time and, more importantly, altered the instantaneous
relation between repolarization and refractoriness. The latter allowed
earliest capture by consecutive extrastimuli to occur at progressively
less complete repolarization levels. Progressive encroachment of
earliest capture toward more incompletely repolarized potentials was
associated with a progressive slowing of impulse propagation. This
observation may help us to understand the mechanism by which programmed
stimulation induces VT in patients with reentry substrates. It would be
of interest to learn how antiarrhythmic drugs modulate this relation,
especially those drugs that successfully suppress VT induction by
altering the ERP/APD relation. Such a study is currently under way in
our laboratory.
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Acknowledgments |
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Bettina S. Koller was supported by a fellowship from the Deutsche Forschungsgemeinschaft, Bonn, Germany. We appreciate the technical assistance of Frankie Hayes, RN, and Mary Chavez.
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Footnotes |
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Reprint requests to Michael R. Franz, MD, PhD, Cardiology Division, Veterans Administration Medical Center, 50 Irving St NW, Washington, DC 20422.
Dr Franz was a consultant for EP Technologies.
Received August 29, 1994; revision received November 17, 1994; accepted November 26, 1994.
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References |
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1. Wellens HJJ, Brugada P, Stevenson WG. Programmed electrical stimulation of the heart in patients with life-threatening ventricular arrhythmias: what is the significance of induced arrhythmias and what is the correct stimulation protocol? Circulation. 1985;72:1-7.
2. Schoenfeld MH, McGovern B, Garan H, Ruskin JN. Long-term reproducibility of response to programmed electrical cardiac stimulation in spontaneous ventricular tachyarrhythmias. Am J Cardiol. 1984;54:564-568. [Medline] [Order article via Infotrieve]
3. McPherson LA, Rosenfeld LE, Batsford WE. Day-to-day reproducibility of responses to right ventricular programmed electrical stimulation: implications for serial drug testing. Am J Cardiol. 1985;55:689-695. [Medline] [Order article via Infotrieve]
4.
Berger MD, Waxman HL, Buxton AE, Marchlinski FE, Josephson
ME. Spontaneous compared with induced onset of sustained ventricular
tachycardia. Circulation. 1988;78:885-892.
5. Cooper MJ, Hunt LJ, Richards DA, Denniss RA, Uther JB, Ross DL. Effect of repetition of extrastimuli on sensitivity and reproducibility of mode of induction of ventricular tachycardia by programmed stimulation. J Am Coll Cardiol. 1988;11:1260-1267. [Abstract]
6. Hoffman BF, Cranefield PF. Electrophysiology of the Heart. Mount Kisco, NY: Futura Publishing Co; 1960:222-227.
7.
Davidenko JM, Antzelevitch C. Electrophysiological mechanisms
underlying rate-dependent changes of refractoriness in normal and
segmentally depressed canine Purkinje fibers: the characteristics of
post-repolarization refractoriness. Circ Res. 1986;58:257-268.
8.
Franz MR, Costard A. Frequency-dependent effects of quinidine
on the relation between action potential duration and refractoriness in
the canine heart in situ. Circulation. 1988;77:1177-1184.
9. Franz MR, Chin MC, Sharkey HR, Griffin JC, Scheinman MM. A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo. J Am Coll Cardiol. 1990;16:878-886. [Abstract]
10. Lee RJ, Liem LB, Cohen TJ, Franz MR. Relation between repolarization and refractoriness in the human ventricle: cycle length dependence and effect of procainamide. J Am Coll Cardiol. 1992;19:614-618. [Abstract]
11. Boyett MR, Jewell BR. Analysis of the effects of changes in rate and rhythm upon electrical activity in the heart. Prog Biophys Mol Biol. 1980;36:1-52. [Medline] [Order article via Infotrieve]
12. Gottlieb C, Josephson ME. The preference of programmed stimulation-guided therapy for sustained ventricular arrhythmias. In: Brugada P, Wellens HJJ, eds. Cardiac Arrhythmias: Where to Go From Here? Mount Kisco, NY: Futura Publishing Co; 1987:421-434.
13. Franz MR. Method and theory of monophasic action potential recording. Prog Cardiovasc Dis. 1991;33:347-368. [Medline] [Order article via Infotrieve]
14.
Franz MR, Bargheer K, Rafflenbeul W, Haverich A, Lichtlen PR.
Monophasic action potential mapping in human subjects with normal
electrocardiograms: direct evidence for the genesis of the T wave.
Circulation. 1987;75:379-385.
15.
Watanabe T, Rautaharju PM, McDonald TF. Ventricular action
potentials, ventricular extracellular potentials, and the guinea-pig.
Circ Res. 1985;57:362-370.
16.
Franz MR, Burkhoff D, Spurgeon H, Weisfeldt ML, Lakatta EG. In
vitro validation of a new catheter technique for recording
monophasic action potentials. Eur Heart J. 1986;7:34-41.
17.
Franz MR, Flaherty JT, Platia EV, Bulkley BH, Weisfeldt ML.
Localization of regional myocardial ischemia by recording of monophasic
action potentials. Circulation. 1984;69:593-604.
18. Franz MR. Long-term recording of monophasic action potentials from human endocardium. Am J Cardiol. 1983;51:1629-1634.[Medline] [Order article via Infotrieve]
19.
Franz MR, Schaefer J, Schottler M, Seed WA, Noble MI.
Electrical and mechanical restitution of the human heart at different
rates of stimulation. Circ Res. 1983;53:815-822.
20. Franz MR, Swerdlow CD, Liem LB, Schaefer J. Cycle length dependence of human action potential duration in vivo: effects of single extrastimuli, sudden sustained rate acceleration and deceleration, and different steady-state frequencies. J Clin Invest. 1988;82:972-979.
21. Dangman KH, Hoffman BF. In vivo and in vitro antiarrhythmic and arrhythmogenic effects of N-acetyl procainamide. J Pharmacol Exp Ther. 1981;217:851-862. [Abstract]
22.
Thompson KA, Blair IA, Woosley RL, Roden DM. Comparative in
vitro electrophysiology of quinidine, its major metabolites and
dihydroquinidine. J Pharmacol Exp Ther. 1987;241:84-90.
23. Weidmann S. The effect of the cardiac membrane potential on the rapid availability of the sodium-carrying system. J Physiol. 1955;127:213-224.
24.
Brown AM, Lee KS, Powell T. Sodium currents in single heart
muscle cells. J Physiol (Lond). 1981;318:479-500.
25.
Kobayashi Y, Peters W, Khan SS, Mandel WJ, Karagueuzian HS.
Cellular mechanisms of differential action potential restitution in
canine ventricular muscle cells during single versus double premature
stimuli. Circulation. 1992;86:955-967.
26.
Han J, Moe GK. Nonuniform recovery of excitability in
ventricular muscle. Circ Res. 1964;14:44-60.
27.
Rensma PL, Allessie MA, Lammers WJEP, Bonke FIM, Schalij MJ.
Length of excitation wave and susceptibility to reentrant atrial
arrhythmias in normal conscious dogs. Circ Res. 1988;62:395-410.
28.
Peon J, Ferrier GR, Moe GK. The relationship of excitability
to conduction velocity in canine Purkinje tissue. Circ
Res. 1978;43:125-135.
29. Van Dam RT, Moore NE, Hoffman BF. Initiation and conduction of impulses in partially depolarized cardiac fibers. Am J Physiol. 1963;204:1133-1144.
30.
Kuo CS, Atarashi H, Reddy CP, Surawicz B. Dispersion of
ventricular repolarization and arrhythmia: study of two consecutive
ventricular premature complexes. Circulation. 1985;72:370-376.
31.
Avitall B, McKinnie J, Jazayeri M, Akhtar M, Anderson A, Tchou
P. Induction of ventricular fibrillation versus monomorphic ventricular
tachycardia during programmed stimulation: role of premature beat
conduction delay. Circulation. 1992;85:1271-1278.
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