(Circulation. 1997;96:4036-4043.)
© 1997 American Heart Association, Inc.
Articles |
Activation-Repolarization Coupling in the Normal Swine Endocardium
From the Cardiovascular System Laboratory, the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; and the Harvard-Thorndike Electrophysiology Institute, Beth Israel Hospital, Boston, Mass.
Correspondence to Shlomo A. Ben-Haim, MD, DSc, Cardiovascular System Laboratory, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron Street, POB 9649, 31096 Haifa, Israel. E-mail sol{at}biomed.technion.ac.il
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background While abnormalities of activation and repolarization play an important role in arrhythmogenesis, little information is available on the interaction between their spatial dispersions in the heart. This study examined the effects of activation spread on the spatial distribution of the repolarization properties during different depolarization patterns.
Methods and Results Left ventricular (LV) endocardial activation and repolarization patterns were mapped in 13 healthy pigs. LV local activation, repolarization, and activation-recovery interval (ARI) times were determined from the intracardiac unipolar electrograms, color-coded, and superimposed on a three-dimensional anatomic map of the ventricle generated with a nonfluoroscopic mapping system. ARI values correlated with the duration of monophasic activation potential recorded from onset of activation to time of 90% repolarization (r=.97, P<.01). Activation time range of the left ventricle was 42±5 ms (mean±SEM) during sinus rhythm and 54±5 ms during right ventricular septal pacing. ARI inversely correlated with the corresponding activation times during both sinus (r2=.76±.03) and paced (r2=.77±.02) rhythms. The longest ARIs were located at the sites of earliest activation and shortest at the latest activation areas, with gradual shortening between them.
Conclusions The spatial distribution of repolarization is dependent on the activation pattern. Repolarization dispersion in the healthy swine heart is relatively small as the result of tight coupling of the action potential duration to the activation process, assigning longer ARIs to sites activated earlier. This coupling reduces global and regional dispersion of repolarization and may serve as an important antiarrhythmic mechanism present in normal myocardium.
Key Words: action potentials • electrophysiology • repolarization • anisotropy • mapping
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Changes in myocardial activation and repolarization may contribute to the genesis of ventricular arrhythmias.1–3 Ventricular tachycardia in patients with coronary artery disease and previous myocardial infarction is generally believed to be reentrant and accompanied mainly by abnormalities of activation.4 In contrast, ventricular arrhythmias in patients with long-QT syndrome, without structural heart disease, is thought to be more closely related to abnormalities of ventricular repolarization.5 It is generally believed that in many cases of ventricular arrhythmia both mechanisms are involved and that they tend to be mutually interdependent.3
Although endocardial activation patterns have been measured in numerous studies, relatively little information exists regarding the spatial dispersion of repolarization. Likewise, there is almost no information in the literature regarding the effect of endocardial activation sequence on the repolarization pattern. In several different models it has been shown that the known nonuniform anisotropic nature of myocardial structure affects activation spread by electrotonic currents.6–11 Furthermore, the effect of electrotonic currents related to the activation spread on the repolarization properties have been reported in some studies.12–16 These studies have demonstrated that activation sequence affects the spatial distribution of repolarization times in isolated tissue preparations and in a small or limited number of sites on the epicardium. Since both slow conduction and nonuniformity of repolarization are important in the genesis of reentry, such interactions may have important clinical implications. However, there has been no systematic study in the whole-animal model of the effects of activation sequence on the global distribution of repolarization times of the endocardium. The aim of this study was to examine the effects of the activation sequence on the spatial distribution of repolarization, both globally and regionally, in the normal heart.
A nonfluoroscopic, catheter-based endocardial mapping technique was used to generate three-dimensional electroanatomic maps of activation, repolarization, and ARI patterns. The system uses magnetic technology to establish the instantaneous location and orientation of a catheter tip and simultaneously records the local electrogram from the same site.17–19 By combining spatial and electrophysiological information from a plurality of endocardial sites, we were able to assess the three-dimensional patterns of activation and repolarization during different activation patterns.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animal Model
Thirteen healthy male pigs (30 to 40 kg) were premedicated with ketamine HCl (20 mg/kg IM) and xylazine (2 mg/kg), anesthetized with pentobarbital (30 mg/kg), intubated, and ventilated with a Harvard large-animal mechanical respirator. Vascular access was obtained using a cut-down procedure for the jugular vein and carotid artery. All procedures were approved by the Ethics Committee of the Technion Faculty of Medicine, Haifa, Israel, and conform with American Physiological Society standards for use of animals in research.
LV Endocardial Mapping
An 8F locatable-tip bipolar
electrophysiological catheter (NAVI-STAR,
Cordis-Webster) was inserted into the RV apex or the coronary
sinus to serve as a reference catheter. With the use of fluoroscopy, a
similar mapping catheter was introduced retrogradely into the LV.
The mapping system (CARTO; Biosense) uses a magnetic field to accurately determine the location and orientation of the two catheter tips, each with 6 degrees of freedom (x, y, z, roll, yaw, and pitch). The cardiac cycle–gated location of the mapping catheter tip is recorded relative to the location and orientation of the intracardiac reference catheter, thus compensating for both animal and cardiac motion. Choosing the R wave as the gating fiducial point results in the acquisition of end-diastolic locations, allowing for reconstruction of the ventricular geometry at end diastole. The catheter is dragged over the endocardium, sequentially acquiring its tip location together with the local electrogram sensed while in contact with the endocardium. We acquired data from 50 to 70 distinct sites. The data were recorded, compiled, and displayed in real time. Sites were included in the map only if the distance between two consecutive end-diastolic locations of the mapping catheter was <2 mm.
Local Activation and Repolarization Measurements
The LAT at each site was determined as the time interval between
the fiducial point on the body-surface ECG and the steepest negative
intrinsic deflection (dV/dtmin) from the unipolar
intracardiac recording (filtered at 0.5 to 400 Hz).
The LRT was determined from the local T wave with the method described
by Wyatt et al.20,21 The fiducial point on the
surface ECG was used as the reference time for all measured intervals.
The local T wave measured from a unipolar electrogram demonstrated one
of three different morphologies: positive, negative, and biphasic. The
dV/dtmax was used to define local repolarization
for negative and biphasic T waves (Fig 1
, a
and b). For positive T waves, the dV/dtmin on the
descending limb of the T wave (Fig 1c) was
used.22
|
ARI was calculated as the time difference between LAT and LRT at each site. ARI has previously been shown to correlate well with APD.20–23 The electrophysiological information was color-coded in real time and superimposed on the three-dimensional geometry of the chamber.
Mapping Protocol
We mapped the hearts during SR (n=8), during RV midseptal pacing
at different CLs (300 and 350 ms, n=13), and during atrial pacing (350
and 400 ms, n=6). The range of activation times, repolarization times,
and ARIs were quantified. In addition, detailed three-dimensional
electroanatomic maps of the patterns of activation, repolarization, and
ARI were generated.
Correlation of ARIs With MAP Recording
In two pigs ARIs were correlated with MAP recordings
with the use of a standard-curve MAP/pacing silver–silver chloride
catheter (EPT). The electrode was positioned gently against the LV
endocardium under fluoroscopic guidance until a stable MAP was
recorded. The mapping catheter was positioned adjacent to the MAP
catheter as judged by using multiplanar fluoroscopy. The time from the
onset of activation to 90% repolarization
(MAP90) was measured as an estimate of
APD.24 ARIs were compared with the
MAP90 at multiple sites and during different
atrial and ventricular pacing rates. A total of 98
recordings at a variety of sites were compared.
RP Maps
In three animals, we also studied the spatial dispersion of RPs
and compared it with the activation sequence of the LV during
ventricular pacing (CL=350 ms). After eight
S1 beats originating from the pacing catheter
(positioned at the RV septum or right atrium), a single premature
stimulus, S2, was given from the mapping catheter
located in the left ventricle. Pacing was delivered at twice
diastolic threshold. The shortest
S1-S2 coupling interval
still inducing a propagated response was measured. The RP at each
measured site in the LV was taken as the shortest
S1-S2 interval that induced
a propagated response, minus the activation time at that site. Since
the activation time at the test site was subtracted from
S1-S2, RPs obtained were
measures of local excitation of each site. By sequentially using this
technique in an average of 20 sites in the LV, we were able to
reconstruct three-dimensional maps of RPs during both atrial and
ventricular pacing.
Statistical Analysis
All data are reported as mean±SEM. Paired data comparing
MAP90 to ARIs were analyzed by linear
regression analysis. Correlations were examined for each of the
three separate T-wave morphologies, as well as for the pooled data,
using Pearson's correlation test. The correlation between activation
times and ARIs for each individual map was calculated using linear
regression analysis.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Endocardial Activation Patterns
The LV activation pattern was studied during SR, right atrial pacing, and ventricular pacing from the RV septum.
Activation of the LV During SR and Atrial Pacing
Fig 2a represents a
typical activation map of the left ventricle during SR. The earliest
activation site (represented by red) was located in the
anterosuperior septal region in all maps. In some hearts, a second
endocardial breakthrough was noted in the posterosuperior septum. Rapid
conduction was noted from the earliest site of activation toward the
apex. The activation then spread significantly slower to the rest of
the endocardium, with the posterior basal wall, the
atrioventricular ring, being activated
last.
|
Total activation time of the LV during SR was 42±5 ms and during atrial pacing was 40±3 and 48±6 ms at CLs of 350 and 400 ms, respectively. Global activation patterns during SR and atrial pacing at 350 and 400 ms were similar.
Activation of the LV During Ventricular Pacing
Fig 3a shows a right anterior
oblique view of a typical three-dimensional activation map of the LV
during pacing from the RV inferomedial septum. The map was
reconstructed with the use of 50 sampled points. As can be seen, the
earliest site of activation (represented by the area in
red) was located in the inferior septum adjacent to the
pacing site. Activation then spread throughout the ventricle, with the
posterolateral areas (indicated by the blue and purple) being
activated last. Intermediate LATs (green and yellow) were
recorded from the remainder of the LV. An important feature that
can be appreciated in these activation maps is
conduction anisotropy, with more rapid conduction in the longitudinal
direction. The total activation time of the ventricle depicted in Fig 3a was 61 ms. Mean activation time range of the LV during pacing was
56±3 and 50±4 ms, with CLs of 350 and 300 ms, respectively. The
activation sequence during ventricular pacing at 300 or 350
ms was similar.
|
Endocardial Repolarization Patterns
T-Wave Morphology Distribution
Local T waves were classified as negative, positive, and
biphasic (Fig 1
, a through c). These different morphologies were
spatially arranged in clusters within the LV. During RV pacing, most of
the T waves were negative, with the positive T waves being concentrated
mainly in the area of earliest activation. During SR and atrial pacing,
most sites exhibited positive T waves, while sites distant from the
earliest sites of activation displayed negative T waves.
Correlation Between ARI and MAP90
A total of 98 MAP recordings and corresponding ARIs
were compared during SR and pacing. The correlation between the
MAP90 and ARIs (Fig 4)
was statistically significant for each of the three T-wave morphologies
and for the pooled data. The overall correlation coefficient was .97
(P<.01), and the correlation coefficients for the positive,
negative, and biphasic T waves were .98 (P<.01), .98
(P<.01), and .94 (P<.01), respectively.
|
ARI Maps
Figs 2b and 3b illustrate typical ARI maps of the LV during SR and
RV septal pacing, respectively. The ARI maps closely resembled the
corresponding activation maps (Figs 2a and 3a), with the longest ARIs
located near the earliest sites of activation (red) and shorter ARIs
observed as activation proceeds from this site. For
example, the longest ARI (307 ms) during RV pacing (red) was located in
the inferior septum (Fig 3), whereas the shortest ARI (229
ms) was located in the posterior and inferolateral regions (purple
area), with a gradient of ARIs between them. The range of the LV ARI
was 65±5 ms [182±8 (mean shortest ARI) to 247±12 ms (mean longest
ARI)] during pacing at 350-ms CL and 50±5 ms (164±9 to 208±9 ms)
during pacing at 300 ms.
During SR and atrial pacing, the ARI maps also resembled the activation
maps. The longest ARIs were located in the septal region, and the
shorter ARIs were located on the lateral wall and close to the mitral
annulus (Fig 2). The range of LV ARI during SR was 63±7 ms (270±16 to
331±20 ms) and during atrial pacing was 36±3 ms (198±12 to 234±11
ms) and 48±10 ms (221±14 to 269±23 ms) at 350- and 400-ms CLs.
To quantify the relationship between the activation sequence and
the spatial dispersion of ARI, detailed plots of the ARIs as a function
of the activation times for each map were generated. Fig 5 represents a typical plot of the
ARI as a function of the activation time, in one animal, during SR and
ventricular pacing. Note the inverse correlation
(r2=.83, .79) for both rhythms. A similar
inverse correlation was found in all animals during SR
(r2=.76±.03), ventricular
pacing (r2=.77±.02 and .76±.02 at CLs of
350 and 300 ms, respectively), and atrial pacing
(r2=.70±.03 and .73±.03 at CLs of 400 and
350 ms, respectively).
|
Repolarization Maps
Figs 2c and 3c display examples of repolarization maps of the LV
generated during SR and RV pacing. The range of T-wave dispersion was
small, averaging <40 ms. The total dispersion of repolarization during
ventricular pacing was 37±3 and 30±3 ms at CLs of 350 and
300 ms, respectively. The dispersion during SR was 39±4 ms and during
atrial pacing was 27±3 and 27±2 ms at CLs of 400 and 350 ms,
respectively. Three patterns of repolarization were noted. In most
maps, the repolarization sequence resembled that of activation; in
others the sequence was reversed, whereas in some cases the earliest
repolarization site was located between the earliest and latest
activation sites.
RP Maps
In three animals, RP maps of the LV were generated during
ventricular pacing (CL=350 ms). Figs 6a and 6b represent activation and RP
maps of the LV during RV septal pacing. The RP at each
site was taken as the shortest
S1-S2 interval that induced
a propagated response, minus the LAT (S1, pacing
from the RV septum; S2, pacing from the mapping
catheter). The RP maps resembled the activation maps, with longer RPs
(red area in Fig 6b) located near the earliest site of activation (red
area in Fig 6a) and shorter RPs located at sites activated
later (purple areas).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Pattern of Ventricular Activation
The endocardial activation sequence of the swine LV was similar during SR and atrial pacing. The earliest activation site was at the anterosuperior septum, occasionally with a second endocardial depolarization noted more posteriorly. Activation then spread to the remainder of the ventricle, in the direction of the apex, atrioventricular ring, the posterolateral wall, and the outflow tract. The observed sequence of activation of the swine LV resembles the classic description of human LV activation given by Durrer et al.25 Conduction anisotropy was obvious, with faster conduction velocity in the longitudinal direction toward the apex and slower activation proceeding transversely. This anisotropy may represent the effects of endocardial activation after the activation of the left anterior and posterior fascicles of the left bundle.
During pacing from the RV inferior septum, LV activation was first noted from the inferior septum, adjacent to the pacing electrode. Activation then proceeded throughout the rest of the ventricle.
Local T-Wave Morphologies
Examination of the local electrograms revealed three types of
T-wave morphologies, characterized by positive, negative, and biphasic
wave forms. We found that there was a nonuniform distribution of the T
wave, with clustering of sites with positive T-wave morphologies near
the earliest activation site and negative or biphasic T waves at sites
that were activated last. This observation is in agreement with
previous animal and human studies performed both in vitro and in
vivo.22,26–29 According to studies performed
with isolated papillary muscle, the morphologies of local T waves were
determined by the spatial relation that exists between the wave of
excitation and the recording electrode.27
The T-wave polarity was positive when the recording electrode
was near the origin of the activation and negative when it was opposite
the origin of activation. Similarly, transmural recording
showed that in normal beats there was transmural unidirectional
gradient, with the inner wall being more negative and the outer wall
more positive.28
Dispersion of ARIs During Both SR and Paced Rhythms
The spatial pattern of ARI was generally similar to the
depolarization pattern. A uniform and homogenous gradient of ARI was
observed, with the longest ARI positioned near the area of earliest
activation, gradually shortening with increased distance from this
site. To further quantify the relationship between the depolarization
sequence and the pattern of ARI, detailed plots correlating the
activation times with the time to ventricular
repolarization (ARI) at each site were determined for each individual
heart. A significant inverse correlation was found between the
activation sequence and ARI for all rhythms
(r2=.77±.02 and .76±.02 for
ventricular pacing at CLs of 400 and 350 ms, respectively;
r2=.76±.03 for SR and
r2=.70±.03 and .73±.03 for atrial pacing
at CLs of 400 and 350 ms, respectively).
Previous studies reported the electrotonic effects of propagation of activation on the dispersion of RP and APD. These studies included in vitro13,16,30,31 and in vivo12,32,33 studies and computer simulations.15,31,32 The shortening of ventricular APD as activation proceeds was noted previously in some of these studies. Specifically, Zubair et al33 studied the effect of the activation sequence of the spatial dispersion of RP at 36 sites within a 1-cm2 region of the epicardial surface of a canine pulmonary conus. They found that the spatial distribution of RPs was markedly affected by the activation spread. Similarly, Osaka et al13 examined the influence of the activation sequence on action potential configuration in the epicardial surface of isolated pieces (2.5 cm2) of canine ventricular muscle. They found that APD shortened gradually as the recording site was moved further from the stimulation site. The spatial gradient of APD was steeper in the transverse than in the longitudinal direction. They speculated that the changes in APD might be due to electrotonic interactions between neighboring cells.
This study is the first report on the effects of activation spread on the spatial distribution of in vivo global endocardial repolarization properties. The first finding in this study is that marked changes in the spatial distribution of ARI occurred when the activation pattern changed. A second novel finding of this study is the observed coupling between ARI and activation sequence, resulting in a relatively simultaneous termination of repolarization. This study demonstrated that the previously reported relationship between ARI and activation sequence is of global significance and not only of local importance.
The marked changes at the spatial distribution of the time to ventricular repolarization (ARI) as a function of the depolarization sequence did not require long-standing alteration of ventricular activation sequence (repolarization memory). In 1982, Rosenbaum et al34 reported that rapid atrial or ventricular pacing in humans could induce T-wave changes that develop to a maximum in about 24 hours of pacing. As reviewed by Katz,35 these changes, referred to as cardiac "memory," develop more slowly and persist longer than the transient changes mediated by cellular metabolism but are still reversible, are not associated with organ damage, and may arise from structural changes in the membrane channel proteins.
The relatively short pacing periods and the lack of changes in T-wave morphologies in the body-surface ECG in the postpacing sinus rhythm interval decrease the likelihood that this mechanism was involved in the changes in the repolarization pattern observed in the current study. Furthermore, the fact that the gradient of ARI was always inversely correlated with the activation sequence may further support the role of electrotonic interactions between cells as the major mechanism of the findings of this study.
Significance of Findings
Dispersion of repolarization usually parallels the dispersion of
refractoriness. The dispersion of repolarization is determined by the
regional differences in activation times and APD. Augmented dispersion
of repolarization has been shown to increase the propensity of
ventricular arrhythmias, both
clinically36–39 and in experimental
models.40–42 Examples of experimental models in
which dispersion of repolarization appears to play an important role
include the circus-movement tachycardia induced by Allessie
et al40 in isolated segments of rabbit atrial
tissue and the late ventricular arrhythmias
elicited after the ligation of left anterior descending
coronary artery in dogs.3
In humans, the mechanism of dispersion of repolarization varies with the disease process. Vassallo et al36 measured recovery of excitability at multiple endocardial sites in the LV in three groups of patients. In normal subjects the mean dispersion of full recovery time was 52 ms. In patients with a history of myocardial infarction and sustained ventricular tachycardia, the dispersion of recovery time was 90 ms, due mainly to prolonged activation time. In contrast, patients with long-QT syndrome demonstrate prolonged dispersion of recovery times (114 ms), primarily because of variable refractoriness.
The current study has shown that in the normal swine heart, dispersion of repolarization in the LV is relatively homogeneous and in most cases does not exceed 40 to 50 ms. This study has reported for the first time the close dependency of local repolarization on the activation process of the entire LV endocardium. We have demonstrated that in the normal swine LV endocardium, the dispersion of repolarization is functionally dependent on the location of earliest activation and the direction of the wave front of propagation. Sites closer to the earliest activation have longer ARIs, whereas sites further away from the activation source have significantly shorter ARIs. Shortening of the APD along the propagation route seems to partially compensate for the delay in arrival of activation to remote sites. Therefore, the repolarization process has little or no dispersion relative to that of the activation process. Furthermore, this tight coupling may also be of regional importance because it compensates for activation time differences between adjacent anatomic sites, thereby diminishing regional spatial dispersion of repolarization. This would tend to reduce the propensity for reentrant arrhythmias.
Use of Unipolar Electrograms to Estimate LRTs
The accuracy of repolarization and ARI maps depends on
analysis of the local T wave for calculations of LRT. Unlike
the unipolar recording of depolarization, the local T wave
lacks sharp intrinsic deflection, so that determining the LRT is more
tedious and at times of questionable value. Wyatt et
al20,21 reported a method for determining the LRT
by which the timing of the maximum rate of rise in voltage
(dV/dtmax) in the local unipolar wave form is
used as a surrogate for the recovery from depolarization of the
intracellular action potential. Using this method, experimental studies
in humans and dogs have shown good correlation between the ARI and
local APD, measured by transmembrane action potential or by single
premature stimuli. Millar et al23 and Chen et
al22 reported that for positive T-wave forms,
underestimation of the APD was found by use of the Wyatt method. They
proposed taking the dV/dtmin on the descending
limb of the T wave, reporting better correlation with the APD. We used
this modified approach. For positive T waves we used the Wyatt
approach, whereas for negative T waves we used the Millar approach.
With this method, we found tight correlation with
MAP90 as measured by a MAP catheter with ARI
intervals.
Limitations of the Study
The results of this study depend on several technical
considerations. In contrast to the rapid downstroke of the local action
potential, the low amplitude and broad nature of the local T wave limit
the accuracy of measurements of local repolarization because the timing
of the maximum change in slope is more variable. Furthermore, the
multiple T-wave morphologies preclude the use of a uniform method for
measuring repolarization times.
However, for four reasons we believe that our method for measuring repolarization is accurate. First, we observed reproducible responses within animals and from animal to animal. Second, our results are consistent with published reports demonstrating excellent correlation between ARI and MAP duration, as well as direct measurement of RP. Third, our methods for measuring repolarization times are based on previously validated studies that took into account the variable morphology of the T wave.6–9 Fourth, maps of ARIs and RPs showed similar results.
Clinical Relevance
The association between increased dispersion of repolarization and
arrhythmogenesis is mentioned above. The current study documents a
tight association between activation, propagation, and dispersion of
repolarization. These dependencies may be caused by electrotonic
currents flowing between adjacent cells. In the presence of a pathology
that decreases cell-to-cell conductivity, the effects of these
electrotonic currents may decrease. This, in turn, may cause uncoupling
of the activation and repolarization process and may account for the
observed increased dispersion of repolarization in diseased
myocardium simultaneous with the increased
propensity to arrhythmogenesis. Studying endocardial
activation-repolarization patterns during disease states may therefore
improve our basic understanding of arrhythmogenesis.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
We are grateful to David D. Gutterman, MD, for critical review of the manuscript and to Ruth Singer for editorial assistance.
Received June 12, 1997; revision received July 29, 1997; accepted August 25, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Han J, Moe GH. Nonuniform recovery of excitability
in ventricular muscle. Circ Res. 1964;14:44–60.
[Abstract/Free Full Text]
-
Han J, Garcia de Jalon P, Moe GH. Adrenergic effect on
ventricular vulnerability. Circ Res. 1964;14:516–524.
[Abstract/Free Full Text]
-
Gough WB, Mehra R, Restivo M, Zeiler RH, el-Sherif N.
Reentrant ventricular arrhythmias in the late
myocardial infarction period in the dog: correlation of activation and
refractory maps. Circ Res. 1985;57:432–442.
[Abstract/Free Full Text]
-
Vassallo JA, Cassidy DM, Marchlinski FE, Miller JM,
Buxton AE, Josephson ME. Abnormalities of endocardial activation
pattern in patients with previous healed myocardial infarction and
ventricular tachycardia. Am J
Cardiol. 1986;58:479–484.[Medline]
[Order article via Infotrieve]
-
Schwartz PJ, Locati EH, Napolitano C, Priori SG. The
long QT syndrome. In: Zipes DP, Jalife J, eds. Cardiac
Electrophysiology: From Cell to Bedside. 2nd ed. Philadelphia, Pa:
WB Saunders; 1995:788–811.
-
Allessie MA, Schalij MJ, Kirchhof CJHJ, Boersma L,
Huybers M, Hollen J. Experimental electrophysiology and
arrhythmogenicity: anisotropy and ventricular
tachycardia. Eur Heart J. 1989;10(suppl
E):2–8.
-
Balke CW, Lesh MD, Spear JF, Kadish A, Levine JH,
Moore EN. Effects of cellular uncoupling on conduction in anisotropic
canine ventricular myocardium. Circ
Res. 1988;63:879–892.
[Abstract/Free Full Text]
-
Clerc L. Directional differences of impulse spread in
trabecular muscle from mammalian heart. J
Physiol (Lond). 1976;255:335–346.
[Abstract/Free Full Text]
-
Dillon SM, Allessie MA, Ursell PC, Wit AL. Influences
of anisotropic tissue structure on reentrant circuits in the epicardial
border zone of subacute canine infarcts. Circ Res. 1988;63:182–206.
[Abstract/Free Full Text]
-
Spach MS, Miller WT III, Geselowitz DB, Barr RC,
Kootsey JM, Johnson EA. The discontinuous nature of propagation in
normal canine myocardium: evidence for recurrent
discontinuities of intracellular resistance that affect the membrane
currents. Circ Res. 1981;48:39–54.
[Free Full Text]
-
Spach MS, Miller WT III, Dolber PC, Kootsey JM, Sommer
JR, Mosher CE Jr. The functional role of structural complexities in the
propagation of depolarization in the atrium of the dog: cardiac
conduction disturbances due to discontinuities of effective
axial resistivity. Circ Res. 1982;50:175–191.
[Free Full Text]
-
Burgess MJ, Steinhaus BM, Spitzer KW, Green LS. Effects
of activation sequence on ventricular refractory periods of
ischemic canine myocardium. J
Electrocardiol. 1985;18:323–329.[Medline]
[Order article via Infotrieve]
-
Osaka T, Kodama I, Tsuboi N, Toyama J, Yamada K.
Effects of activation sequence and anisotropic cellular geometry on the
repolarization phase of action potential of dog ventricular
muscles. Circulation. 1987;76:226–236.
[Abstract/Free Full Text]
-
Toyoshima H, Burgess MJ. Electrotonic interaction
during canine ventricular repolarization. Circ
Res. 1978;43:348–356.
[Abstract/Free Full Text]
-
Lesh MD, Pring M, Spear JF. Cellular uncoupling can
unmask dispersion of action potential duration in
ventricular myocardium: a computer modeling
study. Circ Res. 1989;65:1426–1440.
[Abstract/Free Full Text]
-
Spach MS, Dolber PC, Heidlage JF. Interaction of
inhomogeneities of repolarization with anisotropic propagation in dog
atria: a mechanism for both preventing and initiating reentry.
Circ Res. 1989;65:1612–1631.
[Abstract/Free Full Text]
-
Ben-Haim SA, Osadchy D, Schuster I, Gepstein L, Hayam
G, Josephson ME. Nonfluoroscopic, in vivo navigation and mapping
technology. Nat Med. 1996;2:1393–1395.[Medline]
[Order article via Infotrieve]
-
Gepstein L, Hayam G, Ben-Haim SA. A novel method
for nonfluoroscopic, catheter-based electroanatomical mapping of the
heart: in vitro and in vivo accuracy results. Circulation. 1997;95:1611–1622.
[Abstract/Free Full Text]
-
Shpun S, Gepstein L, Hayam G, Ben-Haim SA. Guidance of
radiofrequency endocardial ablation with real-time three-dimensional
magnetic navigation system. Circulation.. 1997;96:2016–2021.
[Abstract/Free Full Text]
-
Wyatt RF. Comparison of estimates of activation and
recovery times from bipolar and unipolar electrograms to in vivo
transmembrane action potential duration. Proc IEEE/Engineering in
Medicine and Biology Society, 2nd annual conference, Washington DC;
September 1980:22–25.
-
Wyatt RF, Burgess MJ, Evans AK, Lux RL, Abildskov JA,
Tsutsumi T. Estimation of ventricular transmembrane action
potential duration and repolarization times from unipolar electrograms.
Am J Cardiol. 1981;47:488. Abstract.
-
Chen PS, Moser KM, Dembitsky WP, Auger WR, Daily PO,
Calisi CM, Jamieson SW, Feld GK. Epicardial activation and
repolarization patterns in patients with right ventricular
hypertrophy. Circulation. 1991;83:104–118.
[Abstract/Free Full Text]
-
Millar CK, Kralios FA, Lux RL. Correlation
between refractory periods and activation-recovery intervals from
electrograms: effects of rate and adrenergic interventions.
Circulation. 1985;72:1372–1379.
[Abstract/Free Full Text]
-
Franz MR. Long-term recording of monophasic
action potential from human endocardium. Am J Cardiol. 1963;51:1629–1634.
-
Durrer D, van Dam RT, Freud GE, Janse MJ, Meijler FL,
Arzbaecher RC. Total excitation of the isolated human heart.
Circulation. 1970;41:899–912.
[Abstract/Free Full Text]
-
Spach MS, Barr RC. Origin of epicardial ST-T wave
potentials in the intact dog. Circ Res. 1976;39:475–487.
[Abstract/Free Full Text]
-
Hoffman B, Suckling EE. Effect of heart rate on cardiac
membrane potentials and the unipolar electrogram. Am J
Physiol. 1954;179:123–130.
-
Spach MS, Barr RC. Ventricular intramural
and epicardial potential distributions during ventricular
activation and repolarization in the intact dog. Circ Res. 1975;37:243–257.
[Abstract/Free Full Text]
-
Spach MS, Barr RC. Analysis of
ventricular activation and repolarization from intramural
and epicardial potential distributions for ectopic beats in the intact
dog. Circ Res. 1975;37:830–843.
[Abstract/Free Full Text]
-
Joyner R. Modulation of repolarization by electrotonic
interactions. Jpn Heart J. 1986;17(suppl 1):167.
Abstract.
-
Steinhaus BM, Spitzer KW, Isomura S. Action potential
collision in heart tissue–computer simulations and tissue experiments.
IEEE Trans Biomed Eng. 1985;32:731–742.[Medline]
[Order article via Infotrieve]
-
Burgess MJ, Steinhaus BM, Spitzer KW, Ershler PR.
Nonuniform epicardial activation and repolarization properties of in
vivo canine pulmonary conus. Circ Res. 1988;62:233–246.
[Abstract/Free Full Text]
-
Zubair I, Pollard AE, Spitzer KW, Burgess MJ. Effects
of activation sequence on the spatial distribution of repolarization
properties. J Electrocardiol. 1994;27:115–127.[Medline]
[Order article via Infotrieve]
-
Rosenbaum MB, Blanco HH, Elizari MV, Lazzari JO,
Davidenko JM. Electrotonic modulation of the T wave and cardiac memory.
Am J Cardiol. 1982;50:213–222.[Medline]
[Order article via Infotrieve]
-
Katz AM. T wave `memory': possible causal
relationship to stress-induced changes in cardiac ion channels?
J Cardiovasc Electrophysiol. 1992;3:150–159.
-
Vassallo JA, Cassidy DM, Kindwall KE, Marchlinski FE,
Josephson ME. Nonuniform recovery of excitability in the left
ventricle. Circulation. 1988;78:1365–1372.
[Abstract/Free Full Text]
-
Surawicz B. Electrophysiologic Basis of ECG and
Cardiac Arrhythmias. Baltimore, Md: Williams & Wilkins;
1995;242–246.
-
Morgan JM, Cunningham D, Rowland E. Dispersion of
monophasic action potential duration: demonstrable in humans after
premature ventricular extrastimulation but not in steady
state. J Am Coll Cardiol. 1992;19:1244–1253.[Abstract]
-
Misier AR, Opthof T, van Hemel NM, Vermeulen JT, de
Bakker JM, Defauw JJ, van Capelle FJ, Janse MJ. Dispersion of
`refractoriness' in noninfarcted myocardium of patients
with ventricular tachycardia or
ventricular fibrillation after myocardial infarction.
Circulation. 1995;91:2566–2572.
[Abstract/Free Full Text]
-
Allessie MA, Bonke FI, Schopman FJ. Circus
movement in rabbit atrial muscle as a mechanism of
tachycardia, II: the role of nonuniform recovery of
excitability in the occurrence of unidirectional block, as studied with
multiple microelectrodes. Circ Res. 1976;39:168–177.
[Abstract/Free Full Text]
-
Ogawa S, Furuno I, Satoh Y, Yoh S, Saeki K, Sadanaga T,
Katoh H, Nakamura Y. Quantitative indices of dispersion of
refractoriness for identification of propensity to re-entrant
ventricular tachycardia in a canine model of
myocardial infarction. Cardiovasc Res. 1991;25:378–383.
[Abstract/Free Full Text]
-
Kuo CS, Munakata K, Reddy CP, Surawicz B.
Characteristics and possible mechanism of ventricular
arrhythmia dependent on the dispersion of action potential
durations. Circulation. 1983;67:1356–1367.
[Abstract/Free Full Text]
This article has been cited by other articles:
 |
|
 |
|
  S. E. Ahlberg, A. M. Yue, N. D. Skadsberg, P. R. Roberts, P. A. Iaizzo, and J. M. Morgan Investigation of pacing site-related changes in global restitution dynamics by non-contact mapping Europace, January 1, 2008; 10(1): 40 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Colli Franzone, L. F. Pavarino, S. Scacchi, and B. Taccardi Monophasic action potentials generated by bidomain modeling as a tool for detecting cardiac repolarization times Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2771 - H2785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Yue, T. R. Betts, P. R. Roberts, and J. M. Morgan Global Dynamic Coupling of Activation and Repolarization in the Human Ventricle Circulation, October 25, 2005; 112(17): 2592 - 2601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Yue, J. R. Paisey, S. Robinson, T. R. Betts, P. R. Roberts, and J. M. Morgan Determination of Human Ventricular Repolarization by Noncontact Mapping: Validation With Monophasic Action Potential Recordings Circulation, September 14, 2004; 110(11): 1343 - 1350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lessick, G. Hayam, A. Zaretsky, S. A. Reisner, Y. Schwartz, and S. A. Ben-Haim Evaluation of inotropic changes in ventricular function by NOGA mapping: comparison with echocardiography J Appl Physiol, August 1, 2002; 93(2): 418 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gepstein, G. Hayam, S. Shpun, D. Cohen, and S. A. Ben-Haim Atrial Linear Ablations in Pigs : Chronic Effects on Atrial Electrophysiology and Pathology Circulation, July 27, 1999; 100(4): 419 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gepstein, A. Goldin, J. Lessick, G. Hayam, S. Shpun, Y. Schwartz, G. Hakim, R. Shofty, A. Turgeman, D. Kirshenbaum, et al. Electromechanical Characterization of Chronic Myocardial Infarction in the Canine Coronary Occlusion Model Circulation, November 10, 1998; 98(19): 2055 - 2064. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||