(Circulation. 1996;93:372-379.)
© 1996 American Heart Association, Inc.
Articles |
Cellular Basis for the Electrocardiographic J Wave
From the Masonic Medical Research Laboratory, Utica, NY.
Correspondence to Dr Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13504.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background The J wave is a deflection that appears in the ECG as a late delta wave following the QRS or as a small secondary R wave (R'). Also referred to as an Osborn wave, the J wave has been observed in the ECG of animals and humans for more than four decades, yet the mechanism underlying its manifestation is poorly understood. The present study investigates the cellular basis for the J wave using an isolated arterially perfused preparation consisting of a wedge of canine right or left ventricle.
Methods and Results A 12-lead ECG was initially recorded in vivo. After isolation and arterial perfusion of the right or left ventricular wedge, transmembrane action potentials were simultaneously recorded from epicardial, M region, and endocardial transmural sites with three floating microelectrodes. A transmural ECG was recorded concurrently. A J wave was observed at the R-ST junction of the ECG in 17 of 20 adult dogs, usually in leads II, III, aVR, and aVF and the mid to lateral precordial leads. The J wave in the transmural ECG recorded across the wedge was closely associated with the presence of a prominent action potential notch in epicardium but not endocardium. The shape and amplitude of the J wave were found to depend on (1) the transmural distribution of the action potential notch amplitude, (2) the relative time course of the early phases of the action potential (width of notch) at different sites within the wall, (3) sequence of activation, and (4) conduction time across the wall. A highly significant correlation was demonstrated between the amplitude of the epicardial action potential notch and the amplitude of the J wave recorded during interventions that alter the appearance of the electrocardiographic J wave, including hypothermia, premature stimulation, and block of the transient outward current by 4-aminopyridine. Ventricular activation from endocardium to epicardium, with epicardium activated last, was also an important prerequisite for the appearance of the J wave. This sequence permits the establishment of a voltage gradient of the early phases of the action potential after activation (ie, the QRS) is complete.
Conclusions Our results provide the first direct evidence in support of the hypothesis that heterogeneous distribution of a transient outward current–mediated spike-and-dome morphology of the action potential across the ventricular wall underlies the manifestation of the electrocardiographic J wave. The presence of a prominent action potential notch in epicardium but not endocardium is shown to provide a voltage gradient that manifests as a J (Osborn) wave or elevated J-point in the ECG.
Key Words: electrophysiology • electrocardiography • action potentials • arrhythmia • reentry
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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The J wave is a deflection that appears in the ECG as a late delta wave following the QRS or as a small secondary R wave (R'). Also referred to as the Osborn wave, the J wave or elevated J-point has been described in the ECG of animals and humans for more than four decades,1 since Osborn's observation in the early 1950s.2 In humans, the appearance of a prominent J wave in the ECG is considered pathognomonic of hypothermia3 4 5 6 and hypercalcemia.7 8 A distinct J wave or elevated J-point has been described in subjects completely recovered from hypothermia9 10 or those predisposed to early repolarization syndrome,11 12 but it is otherwise rarely observed in humans under normal conditions. In animals, a distinct J wave is commonly observed in the ECG of some species, including baboons and dogs, under baseline conditions and is greatly amplified under hypothermic conditions.13 14 15 An elevated J-point is commonly encountered in humans and some animal species under normal conditions.
A more prominent Ito-mediated spike-and-dome action potential morphology in ventricular epicardium than in endocardium has been proposed as the cellular electrophysiological basis for the J wave. The more conspicuous notched configuration of the epicardial response is thought to produce a transmural voltage gradient during ventricular activation that manifests as a J wave or J-point elevation in the ECG.16 17 18 19 Direct evidence in support of the hypothesis, however, has been lacking.
Recently, we developed an isolated, arterially perfused preparation consisting of a wedge of canine ventricle from which one can simultaneously record transmembrane activity from several sites across the ventricular wall together with a transmural ECG. In the present study, we use this preparation to test the hypothesis that the electrocardiographic J wave and elevated J-point are products of a heterogeneous distribution of an Ito-mediated spike-and-dome morphology of the action potential in canine ventricular myocardium.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Arterially Perfused Wedge of Canine Left or Right Ventricle
Dogs weighing 20 to 25 kg were anticoagulated with heparin and anesthetized with pentobarbital (25 mg/kg IV). A 12-lead ECG was obtained (Schiller AG). The chest was opened via a left thoracotomy, and the heart was excised, placed in a cardioplegic solution consisting of cold (4°C) Tyrode's solution containing 8.5 mmol/L [K+]o, and transported to a dissection tray. Transmural wedges with dimensions of approximately 1x1x0.8 or 0.8x0.8x0.4 cm3 were dissected from the left or right ventricles, respectively. The tissue was cannulated via a small (diameter,
100 µm) branch of the left anterior descending
artery or another coronary artery and perfused with
cardioplegic solution. The total period of time from excision of the
heart to cannulation and perfusion of the artery was less than 4
minutes. Unperfused tissue was carefully removed with a razor blade.
The preparation was then placed in a small tissue bath and
arterially perfused with Tyrode's solution of the
following composition (mmol/L): NaCl 129, KCl 4,
NaH2PO4 0.9, NaHCO3 20,
CaCl2 1.8, MgSO4 0.5, glucose 5.5, and insulin
1 U/L, buffered with 95% O2/5% CO2
(36±1°C). The perfusate was delivered to the artery by a
roller pump (Cole Parmer Instrument Co). Perfusion pressure was
monitored with a pressure transducer (World Precision Instruments, Inc)
and maintained between 40 and 50 mm Hg by adjustment of the perfusion
flow rate. The preparations remained immersed in the
arterial perfusate, which was allowed to rise to a
level 2 to 3 mm above the tissue surface (36±1°C).
Recording of the Transmural ECG and Transmembrane
Action Potentials
The ventricular wedges were allowed to
equilibrate in the tissue bath until electrically stable, usually 1
hour. The preparations were stimulated at basic cycle lengths ranging
from 500 to 4000 ms with bipolar silver electrodes insulated except at
the tips and applied to the endocardial surface.
A transmural ECG
signal was recorded with extracellular
silver/silver chloride electrodes placed near the epicardial and
endocardial surfaces of the preparation plugged into a differential DC
amplifier. Transmembrane action potentials were recorded
simultaneously from the epicardial, endocardial, and M
regions by three separate intracellular floating microelectrodes (DC
resistance, 10 to 20 M
) filled with 2.7 mol/L KCl and connected to a
high-input impedance amplifier. Impalements were obtained from the
cut surface of the preparation at positions approximating the
transmural axis of the ECG recording. Amplified signals were
digitized, stored on magnetic media and CD-ROM, and analyzed by
Spike 2 (Cambridge Electronic Designs). The amplitude of the action
potential notch was measured as the voltage difference between the end
of phase 1 and the peak of phase 2 (dome).
Statistics
Statistical analysis of the data was performed
with
Student's t test for paired data. When possible, the data
are presented as mean±SD.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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A prominent J wave was observed in the ECGs of 17 of 20 dogs from which a 12-lead body surface ECG was recorded in vivo. A J wave or J-point elevation was most readily apparent in leads II, III, aVR, aVF, and the precordial leads (V3 through V6). The ECG recorded from the left (lateral) precordial leads usually corresponded well with the transmural ECG recorded from the left ventricular wedge preparations isolated from the same heart, as illustrated in Fig 1
. ECG2, recorded in vivo from
lead V5, displays a J wave (arrow) similar to that
observed in the transmural ECG (ECG1 ) recorded across
the arterially perfused left ventricular wedge
isolated from the same heart (Fig 1). A prominent
spike-and-dome morphology of the transmembrane action potential
in epicardium is coincident with the appearance of a J wave at the R-ST
junction.
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The accentuation or appearance of a J wave is a typical feature of the
ECG in
humans3 6 10 20 21
and animals13 14 15
exposed to cold accidentally or as part of a clinical or experimental
surgical procedure. To examine the relation between alterations of the
electrocardiographic J wave and the configuration of the action
potentials of cells spanning the ventricular wall, we
exposed arterially perfused wedges of canine left ventricle
to hypothermia. In the example illustrated in Fig 2,
only an elevated J-point is observed under normothermic
(36°C) conditions (Fig 2A). The notched configuration of
the action
potential is considerably more prominent in the epicardial response
(top) than in the endocardial action potential. Moreover, the end of
phase 1 of the epicardial action potential is coincident with the peak
of the J-point elevation in the ECG. A decrease in the temperature of
the perfusate and bath to 29°C yields a distinct and
prominent J wave, whose appearance is clearly associated with an
increase in the amplitude and width of the action potential notch in
epicardium but not endocardium (Fig 2B). The effect of
hypothermia was
reversible. Rewarming of the preparation leads to a parallel reduction
in the amplitude of the J wave and that of the notch of the epicardial
action potential (Fig 2C).
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The coincident timing of the epicardial notch and electrocardiographic
J wave suggests that the J wave is caused by a transmural voltage
gradient created by the presence of a notch in the epicardial but not
endocardial layers. As a further test of this hypothesis, we examined
these relations under conditions in which the Ito-mediated
spike-and-dome morphology of the epicardial action potential is
reduced. Fig 3 shows the effect of premature
stimulation, and Fig 4 illustrates direct block of
Ito with 4-AP.
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) and J wave (
) as a function of
the S1-S2 interval. The amplitude of the
epicardial action potential notch and that of the J wave are normalized
to the value recorded at an S1-S2 interval
of 900 ms.
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Due to the slow reactivation kinetics of Ito,
premature stimulation of canine ventricular epicardium
results in a diminution of the action potential notch. In the example
illustrated in Fig 3A
, the smaller notch of the premature beat
is shown
to be attended by a parallel decrease in the magnitude of the J wave
(arrows). Fig 3B plots normalized values of the two
parameters, recorded with premature stimuli applied at
S1-S2 intervals ranging between 250 and 900 ms.
The progressive decrease in the amplitude of the action potential notch
observed at shorter S1-S2 intervals is
accompanied by a similar decrease in the amplitude of the corresponding
J wave. Similar correspondence was observed in five other preparations
in which premature stimulation was used.
In another series of experiments (n=9), we used 4-AP (5 mmol/L) to
directly inhibit Ito and thus abolish or markedly reduce
the action potential notch. Fig 4 shows a
representative example in which reduction of the
epicardial notch is accompanied by a corresponding reduction in the
magnitude of the J wave. It is also noteworthy that 4-AP produces a
prolongation of the APD in endocardium, principally by its action to
inhibit the delayed rectifier current. In contrast, 4-AP produces
little change in the APD of epicardium because it blocks both
Ito and delayed rectifier current in this tissue; these
actions are known to produce opposing effects on APD in canine
epicardium.22 The result is a wider T wave and a prolonged
QT interval. The prominent J waves that appear during hypothermia are
also largely abolished by 5 mmol/L 4-AP (data not shown).
Fig 5 presents a correlation of the changes in
action potential notch and J wave amplitudes recorded during the
various interventions described above (hypothermia, premature
stimulation, and 4-AP). One representative plot is
shown for each intervention (three different preparations). Linear
regression reveals a highly significant correlation (r=.99)
between the two parameters when the
S1-S2 interval or temperature is varied.
Average data for each intervention are shown in the
Table. The average regression slope was 0.017 for 4-AP,
0.010 for the S1-S2 protocol, and 0.009 for the
temperature protocol.
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) and in the
absence and presence of 5 mmol/L 4-AP (
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Role of the Different Cell Types
A spike-and-dome morphology
of the action potential
is clearly present in other than epicardial cells. Cells displaying
a prominent notched configuration have been described in the deep
layers of the endocardial structures of the ventricles of the heart,
including the septum, papillary muscles, and trabeculae, as
well as in cells residing in the deep structures of the free wall,
particularly in the M region.23 24 25
Those residing in the
endocardial layers cannot contribute to the J wave because their action
potential notch normally occurs during activation of the
ventricular wall and thus is embedded in the QRS complex.
Cells in the M region could contribute to the J wave, depending on
phase relationships and activation vectors. With an
endocardial-to-epicardial transmural activation sequence, M
cells in the deep subepicardial layers are likely to contribute to the
manifestation of a J wave in the ECG. The notch of M cells located
deeper in the midmyocardial layers would be expected to contribute to
the voltage gradients and electromotive forces generated during the QRS
and therefore are not likely to influence the appearance of the J wave.
The early repolarization phase of these midmyocardial cells could
theoretically contribute to the J wave if their action potential notch
were able to clear the QRS complex.
To test this hypothesis, we
recorded from an arterially
perfused transmural wedge of canine left ventricle with the wall intact
and the endocardial layers removed (Fig 6). Fig
6A shows
a transmural ECG and three transmembrane traces recorded
simultaneously from the endocardial, M, and epicardial
regions of an intact left ventricular wedge preparation.
The notch of the epicardial action potential is temporally aligned with
a prominent J wave in the ECG (arrow). The notch of the M cell action
potential, however, coincides with the QRS and thus contributes little
if at all to the J wave. The traces in Fig 6B were recorded 60
minutes after 4 mm of the endocardial surface was removed with a
sharp razor blade. The stimulating electrodes were applied to the new
endocardial (midmyocardial) surface, and epicardial and M cell
recordings were obtained from approximately the same sites. The
transmural ECG displays a QRS 35% briefer than in the intact
preparation followed by two J waves, one corresponding to the notch in
the M cell action potential and the other corresponding to the notch in
the epicardial response (arrows). The appearance of the first J wave
seems to be due to the shorter transmural activation as well as to the
widening and accentuation of the notch of the M cell action potential.
The accentuation of the notch and prolongation of the M cell action
potential are both expected as a consequence of the removal of the
electrotonic influences of endocardium (because the intrinsic action
potential of endocardium is relatively brief and largely devoid of a
notch).
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It is of interest that despite the presence of a more
accentuated notch
in epicardium, the corresponding J wave (second arrow) recorded
after removal of endocardium is small compared with that recorded
in the intact preparation (compare Fig 6B with Fig
6A). This
observation serves to highlight the fact that the amplitude of the J
wave is not determined by the amplitude of the spike and dome alone but
rather by the voltage gradient that develops across the
ventricular wall. With endocardium missing, the voltage
gradient between epicardial and M regions was small because of the
presence of an action potential notch in both, resulting in a small J
wave.
The importance of the activation sequence is illustrated in Fig
7. Recordings are from an arterially
perfused canine left ventricular wedge preparation. With an
endocardial-to-epicardial activation sequence, a prominent J
wave, temporally aligned with the notch of the epicardial action
potential, is apparent in the transmural ECG (Fig 7A). When the
sequence is reversed, the notch of the epicardial response is
coincident with the QRS, and a J wave is not observed (Fig 7B).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Using a newly developed arterially perfused canine ventricular wedge preparation, we provide, for the first time, direct evidence in support of the hypothesis that heterogeneous distribution of an Ito-mediated spike-and-dome morphology of the action potential across the ventricular wall underlies the manifestation of the electrocardiographic J wave. The presence of a prominent action potential notch in epicardium but not endocardium is shown to provide a voltage gradient that manifests as a J (Osborn) wave or elevated J-point at the R-ST junction of the ECG.
The ECG waveform is known to depend on the properties of the generator (action potential), the spread of excitation, and the characteristics of the volume conductor.26 Consistent with these basic principles, the shape and amplitude of the J wave were found to depend on (1) the transmural distribution of the action potential notch amplitude, (2) the relative time course of the early phases of the action potential (width of notch) at different sites within the wall, (3) the sequence of activation, and (4) the conduction time across the wall.
Our data demonstrate a highly significant correlation between the
amplitude of the epicardial action potential notch and that of the J
wave recorded during interventions that alter the appearance of the
electrocardiographic J wave, including hypothermia, premature
stimulation, and block of Ito by 4-AP (Figs 1 through
5).
Ventricular activation from endocardium to epicardium, with
epicardium activated last, was an important prerequisite for
the appearance of the J wave. This sequence permits the establishment
of a voltage gradient of the early phases of the action potential after
activation of the preparation (ie, the QRS) is complete, that is, in
the absence of other voltage gradients or electromotive forces.
Accordingly, stimulation of the preparation from an epicardial site did
not produce a J wave despite the maintenance of cellular
differences in the morphology of the action potential (Fig 7).
Conduction time across the wall is another determining factor. Removal
of the endocardial layers abbreviated the QRS and allowed expression of
the notch of the midmyocardial M cells as a J wave in the ECG (Fig
6).
This finding also suggests that ECG expression of the notch in regions
of the myocardium such as right ventricular
epicardium (where the action potential notch is most
prominent27 28 ) may be obscured. Consistent with
previous studies, we found the spike-and-dome morphology of
right ventricular epicardial action potentials to be more
accentuated than that of left ventricular epicardium.
Despite the larger notch, right ventricular epicardium
might be expected to make only a minor contribution to the J wave under
normal conditions. Because of a thinner ventricular wall
and a briefer activation time, the right ventricular
epicardial action potential notch occurs during the QRS generated by
the heart as a whole. The prominent early repolarization and secondary
depolarization phase (notch) of the right ventricular
epicardial response therefore occur during a time when large
electromotive forces and dipoles are generated as a result of continued
spread of excitation in other parts of the heart. Thus, during normal
excitation, these cells would be expected to contribute little to the
manifestation of the J wave.
Taken together, these observations argue for the manifestation of the J wave in ECG leads in which the mean vector axis is transmurally oriented across the left ventricle and septum. It is therefore not surprising that the J wave in the dog is most prominent in leads II, III, aVR, aVF, and mid to left precordial leads V3 through V6. A similar picture is seen in the human ECG.3 6 8 Moreover, vectorcardiography indicates that the J wave forms an extra loop that occurs at the junction of the QRS and T loops.29 It is directed leftward and anteriorly, which explains its prominence in leads associated with the left ventricle.
The electrocardiographic J wave was first noted in animal experiments involving hypercalcemia conducted in the 1920s.7 The first extensive description and characterization appeared 30 years later in a study by Osborn involving experimental hypothermia in dogs.2 As a consequence, this wave, which appears at the R-ST junction, is often referred to as either a J wave or an Osborn wave. Other less frequently used terms include J deflection, camel hump, and elevated J-point.
Earlier studies attributed the J wave to a variety of factors, including anoxia, injury current, acidosis, delayed ventricular depolarization, and early ventricular repolarization.30 31 In the late 1980s, Litovsky and Antzelevitch and colleagues16 32 33 proposed a difference in the electrophysiology of ventricular epicardium and endocardium as the basis for the electrocardiographic J wave. The ionic mechanism underlying the J wave has not been fully elucidated but has been attributed largely to the presence of a 4-AP–sensitive Ito in some myocardial cells but not others, giving rise to a heterogeneous distribution of a spike-and-dome morphology of the action potential.18 33 34 The presence of a prominent Ito is largely responsible for the relatively large phase 1 and the characteristic spike-and-dome (notched) configuration of the epicardial action potential. The absence of a prominent notch in the endocardial action potential is correlated with a much smaller Ito. These regional differences in the contribution of Ito, first suggested on the basis of action potential data,16 have now been demonstrated with whole-cell patch-clamp techniques in feline,35 rabbit,36 canine,34 and human37 ventricular myocytes.
The spike-and-dome morphology of the epicardial action potential is absent in canine neonates, gradually appearing over the first few months of life.18 The progressive development of the notch is paralleled by the appearance of Ito.18 38 39 It is therefore not surprising that a J wave is not observed in neonatal dogs (C.A. et al, unpublished observations).
In humans, the appearance of a prominent J wave has been typically
associated with pathophysiological conditions
such as hypothermia3 6 and
hypercalcemia,7 8
although a small J wave is observed in some patients who have
completely recovered from hypothermia9 10 or those
predisposed to early repolarization syndrome.11 12
Our
results suggest that the very prominent J wave induced by hypothermia
is the result of a marked accentuation of the
spike-and-dome morphology of the action potential of M and
epicardial cells (ie, an increase in both width and amplitude of the
notch). It is tempting to speculate that this is due to the effect of
cold temperatures to slow the kinetics of activation of Ito
less than the kinetics of the ICa. This hypothesis remains
to be tested. In addition to inducing a more prominent notch,
hypothermia produces marked slowing of conduction velocity. The
additional conduction delay from endocardium to epicardium together
with the widening of the epicardial action potential notch can serve to
unmask a latent J wave by moving it out of the QRS complex (Fig
2).
Association of hypercalcemia with the appearance of the J wave7 8 can also be explained on the basis of an accentuation of the spike-and-dome morphology of the epicardial action potential.40 This effect of hypercalcemia is thought to be due to an increase in the net outward current during the early phases of the action potential, possibly due to an increase in calcium-activated chloride current and a decrease in ICa (more rapid inactivation). The presence of a prominent Ito in epicardium sensitizes that tissue to the effects of high calcium concentration.40
Clinical Implications
The presence of a prominent notch has
been shown to
predispose canine ventricular epicardium to
all-or-none repolarization and phase 2 reentry (see References
18, 33, and 41 for reviews). Under ischemic conditions and in
response to a variety of drugs, canine ventricular
epicardium exhibits an all-or-none repolarization at the end of
phase 1 of the action potential. Failure of the dome to develop results
in a marked (40% to 70%) abbreviation of the action potential. Under
these conditions, the action potential plateau (dome) is usually
abolished at some epicardial sites but not others, causing a marked
dispersion of repolarization. Propagation of the action potential dome
from sites at which it is maintained to sites at which it is abolished
can cause local reexcitation of the preparation. This mechanism, called
phase 2 reentry, produces extrasystolic activity, which can
then initiate one or more cycles of circus movement
reentry.42 Electrical heterogeneity
leading to phase 2 reentry has been demonstrated in canine epicardium
exposed to (1) K+ channel openers such as
pinacidil,43 (2) sodium channel blockers such as
flecainide,44 (3) increased
[Ca2+]o,40 (4)
metabolic inhibition,19 and (5) simulated
ischemia.42 Ito blockade restores
electrical homogeneity and abolishes reentrant activity in all
cases.
Because the J wave provides an index of the prominence of the spike-and-dome morphology of the epicardial response, it may prove to be of diagnostic or prognostic value in identifying subjects predisposed to phase 2 reentry or individuals who may be inclined to develop various forms of early repolarization syndrome.
The idiopathic J wave has been linked to life-threatening ventricular arrhythmias such as the Brugada syndrome.45 46 47 48 49 The Brugada syndrome is characterized by a persistent ST-segment elevation in leads V1 through V3 (unrelated to ischemia, electrolyte abnormalities, or structural heart disease), normal QT interval, and sudden cardiac death.46 Apparent right bundle branch block is also present in many but not all cases. Recent data point to similarities between the conditions that predispose to phase 2 reentry and those that attend the appearance of the Brugada syndrome. Loss of the action potential dome (plateau) in epicardium but not endocardium causes elevation of the ST segment or early repolarization syndrome, similar to that found in patients with the Brugada syndrome.19 Because loss of the dome is caused by an outward shift in the balance of currents active at the end of phase 1 of the action potential (principally Ito and ICa), autonomic neurotransmitters like acetylcholine facilitate loss of the action potential dome50 by suppressing ICa, whereas ß-adrenergic agonists restore the dome by augmenting ICa. Sodium channel blockers also facilitate loss of the canine right ventricular action potential dome as a result of a negative shift in the voltage at which phase 1 begins.44 51 Accentuation of the ST-segment elevation in patients with the Brugada syndrome after vagal maneuvers or class I antiarrhythmic agents and reduction of ST-segment elevation after ß-adrenergic agents are consistent with these experimental findings. The appearance of the ST-segment elevation only in right precordial leads is also consistent with the observation that loss of the action potential is usually observed in right but not left ventricular epicardium.19 52 These observations point to a depressed right ventricular epicardial action potential dome as the basis for the ST-segment elevation and phase 2 reentry as a trigger for episodes of ventricular fibrillation in patients with the Brugada syndrome. These hypotheses remain to be investigated.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by grant HL-47678 from the National Institutes of Health; a fellowship award from the American Heart Association, New York State Affiliate, to Dr Yan; and a grant from the Seventh Manhattan Masonic District Association. We are grateful to Drs Weissenburger and Di Diego for their helpful discussions. We also gratefully acknowledge the expert technical assistance of Judy Hefferon, Tengxian Liu, and Robert Goodrow.
Received May 31, 1995; revision received August 14, 1995; accepted September 11, 1995.
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References |
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TopAbstractIntroductionMethods Results Discussion References |
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M. Alings and A. Wilde "Brugada" Syndrome : Clinical Data and Suggested Pathophysiological Mechanism Circulation, February 9, 1999; 99(5): 666 - 673. [Full Text] [PDF]
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P. G. A. Volders, K. R. Sipido, E. Carmeliet, R. L. H. M. G. Spatjens, H. J. J. Wellens, and M. A. Vos Repolarizing K+ Currents ITO1 and IKs Are Larger in Right Than Left Canine Ventricular Midmyocardium Circulation, January 19, 1999; 99(2): 206 - 210. [Abstract] [Full Text] [PDF]
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I. Gussak, C. Antzelevitch, P. Bjerregaard, J. A. Towbin, and B. R. Chaitman The Brugada syndrome: clinical, electrophysiologic and genetic aspects J. Am. Coll. Cardiol., January 1, 1999; 33(1): 5 - 15. [Abstract] [Full Text] [PDF]
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J. Brugada, P. Brugada, and R. Brugada The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome Europace, January 1, 1999; 1(3): 156 - 166. [Abstract] [PDF]
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L. LITTMANN Bifid T waves induced by isoprenaline in a patient with Brugada syndrome Heart, December 1, 1998; 80(6): 633a - 633. [Full Text]
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G.-X. Yan, W. Shimizu, and C. Antzelevitch Characteristics and Distribution of M Cells in Arterially Perfused Canine Left Ventricular Wedge Preparations Circulation, November 3, 1998; 98(18): 1921 - 1927. [Abstract] [Full Text] [PDF]
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G.-X. Yan and C. Antzelevitch Cellular Basis for the Normal T Wave and the Electrocardiographic Manifestations of the Long-QT Syndrome Circulation, November 3, 1998; 98(18): 1928 - 1936. [Abstract] [Full Text] [PDF]
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J. W. Hurst Naming of the Waves in the ECG, With a Brief Account of Their Genesis Circulation, November 3, 1998; 98(18): 1937 - 1942. [Full Text] [PDF]
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J. Feng, L. Yue, Z. Wang, and S. Nattel Ionic Mechanisms of Regional Action Potential Heterogeneity in the Canine Right Atrium Circ. Res., September 7, 1998; 83(5): 541 - 551. [Abstract] [Full Text] [PDF]
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S. Viskin, B. Belhassen, H. Kasanuki, N. Matuda, and S. Ohnishi Increased Vagal Activity in Idiopathic VF • Response Circulation, March 10, 1998; 97 (9): 937 - 940. [Full Text]
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K. Nademanee, G. Veerakul, S. Nimmannit, V. Chaowakul, K. Bhuripanyo, K. Likittanasombat, K. Tunsanga, S. Kuasirikul, P. Malasit, S. Tansupasawadikul, et al. Arrhythmogenic Marker for the Sudden Unexplained Death Syndrome in Thai Men Circulation, October 21, 1997; 96(8): 2595 - 2600. [Abstract] [Full Text]
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W. Shimizu and C. Antzelevitch Sodium Channel Block With Mexiletine Is Effective in Reducing Dispersion of Repolarization and Preventing Torsade de Pointes in LQT2 and LQT3 Models of the Long-QT Syndrome Circulation, September 16, 1997; 96(6): 2038 - 2047. [Abstract] [Full Text]
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P. Bailly, J.-P. Benitah, M. Mouchoniere, G. Vassort, and P. Lorente Regional Alteration of the Transient Outward Current in Human Left Ventricular Septum During Compensated Hypertrophy Circulation, August 19, 1997; 96(4): 1266 - 1274. [Abstract] [Full Text]
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C. Antzelevitch The M Cell Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(1): 73 - 76. [PDF]
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F. G. Akar, G.-X. Yan, C. Antzelevitch, and D. S. Rosenbaum Unique Topographical Distribution of M Cells Underlies Reentrant Mechanism of Torsade de Pointes in the Long-QT Syndrome Circulation, March 12, 2002; 105(10): 1247 - 1253. [Abstract] [Full Text] [PDF]
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K. Gima and Y. Rudy Ionic Current Basis of Electrocardiographic Waveforms: A Model Study Circ. Res., May 3, 2002; 90(8): 889 - 896. [Abstract] [Full Text] [PDF]
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