| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1999;100:1660-1666.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Cellular Basis for the Brugada Syndrome and Other Mechanisms of Arrhythmogenesis Associated With ST-Segment Elevation
From the Masonic Medical Research Laboratory, Utica, NY.
Correspondence to Dr Charles Antzelevitch, Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501. E-mail ca{at}mmrl.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads and is associated with a high incidence of sudden and unexpected arrhythmic death. Our study examines the cellular basis for this syndrome.
Methods and Results—Using arterially perfused wedges of canine right ventricle (RV), we simultaneously recorded transmembrane action potentials from 2 epicardial and 1 endocardial sites, together with unipolar electrograms and a transmural ECG. Loss of the action potential dome in epicardium but not endocardium after exposure to pinacidil (2 to 5 µmol/L), a K+ channel opener, or the combination of a Na+ channel blocker (flecainide, 7 µmol/L) and acetylcholine (ACh, 2 to 3 µmol/L) resulted in an abbreviation of epicardial response and a transmural dispersion of repolarization, which caused an ST-segment elevation in the ECG. ACh facilitated loss of the action potential dome, whereas isoproterenol (0.1 to 1 µmol/L) restored the epicardial dome, thus reducing or eliminating the ST-segment elevation. Heterogeneous loss of the dome caused a marked dispersion of repolarization within the epicardium and transmurally, thus giving rise to phase 2 reentrant extrasystole, which precipitated ventricular tachycardia (VT) and ventricular fibrillation (VF). Transient outward current (Ito) block with 4-aminopyridine (1 to 2 mmol/L) or quinidine (5 µmol/L) restored the dome, normalized the ST segment, and prevented VT/VF.
Conclusions—Depression or loss of the action potential dome in RV epicardium creates a transmural voltage gradient that may be responsible for the ST-segment elevation observed in the Brugada syndrome and other syndromes exhibiting similar ECG manifestations. Our results also demonstrate that extrasystolic activity due to phase 2 reentry can arise in the intact wall of the canine RV and serve as the trigger for VT/VF. Our data point to Ito block (4-aminopyridine, quinidine) as an effective pharmacological treatment.
Key Words: electrophysiology • ventricles • electrocardiography • J wave • fibrillation • tachycardia
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The Brugada syndrome is characterized by marked ST-segment elevation in the right precordial ECG leads (unrelated to ischemia, electrolyte abnormalities, or structural heart disease) and is associated with a high risk for sudden death1 2 3 4 5 6 (for review see References 7 through 97 8 9 ). Although this syndrome is observed worldwide, it is more common in Asian countries, including Thailand, Japan, Laos, Cambodia, Vietnam, the Philippines, and China. It is a leading cause of death among young men in the northeastern region of Thailand (1:2500), second only to automobile accidents.4 However, the mechanisms responsible for the ST-segment elevation and the genesis of ventricular tachycardia/ventricular fibrillation (VT/VF) in this syndrome remain unknown.
It is now well established that a transient outward current (Ito)–mediated phase 1, which gives rise to a notched appearance of the action potential (AP), is more prominent in epicardium than in endocardium of the ventricles of many species. Transmural differences in the contribution of Ito, first suggested in 1988 on the basis of AP data,10 have now been demonstrated by use of whole-cell patch-clamp techniques in canine, feline, rabbit, rat, and human ventricular myocytes. Recent studies also indicate the presence of a much larger Ito-mediated notch in right versus left canine ventricular epicardium.11 For a review, see Reference 99 .
The presence of a prominent AP notch in epicardium but not endocardium causes a transmural voltage gradient during ventricular activation that has been shown to underlie the J-wave and J-point elevation in the ECG.12 The presence of a prominent Ito-mediated notch also predisposes canine ventricular epicardium to all-or-none repolarization under a variety of conditions, including ischemia.13 14 15 16 Loss of the AP dome (plateau) in epicardium but not endocardium produces a voltage gradient during ventricular repolarization that is thought to underlie elevation of the ST segment, similar to that found in patients with the Brugada syndrome. In isolated sheets of canine right ventricular (RV) epicardium, heterogeneous loss of the AP dome has been shown to induce a marked increase in dispersion of repolarization as well as phase 2 reentry, which is responsible for the closely coupled extrasystole that initiates VT.16
A demonstration of these mechanisms in the intact wall of the heart and their direct relationship to the Brugada syndrome has been lacking. The present study uses an arterially perfused wedge preparation to provide a direct test of the hypotheses that depression or loss of the AP dome can occur in ventricular epicardium, that the resultant transmural voltage gradients cause an ST-segment elevation, and that heterogeneous loss of the epicardial AP dome predisposes the ventricle to the development of phase 2 reentrant extrasystoles, which precipitate VT/VF.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Arterially Perfused Wedge of Canine RV
The methods used for isolation, perfusion, and recording of transmembrane activity from the arterially perfused canine RV (anterior wall) wedge preparation, as well as the viability and electrical stability of the preparation, are detailed in previous studies (see References 17 and 1817 18 ). Time controls have demonstrated the electrical stability of the wedge preparations for a period of >4 hours.
Briefly, a transmural wedge of the canine RV free wall was isolated and perfused through a coronary artery. A transmural pseudo-ECG was recorded along the same vector as the transmembrane recordings (Epi: "+" pole). Transmembrane APs were recorded simultaneously from 2 epicardial and 1 endocardial sites by use of 3 separate intracellular floating microelectrodes.
Except where noted, all drugs used in this study were dissolved in Tyrode's solution and infused into the wedge preparation via its native coronary artery. Amplified signals were digitized, stored on magnetic media and CD, and analyzed with Spike 2 (Cambridge Electronic Design).
Statistics
Statistical analysis of the data was performed with a
Student's t test for paired data or 1-way ANOVA coupled
with Scheffé's test. Each wedge preparation served as its own
control. All results are expressed as mean±SD unless otherwise
indicated
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Mechanism Responsible for the ST Elevation
The most prominent ECG feature of the Brugada syndrome is paroxysmal ST-segment elevation in the right precordial leads (V1 through V3),1 2 suggesting the presence of a transmural voltage gradient during repolarization of the RV.
A direct test of this hypothesis is illustrated in Figure 1
, recorded from an
arterially perfused RV wedge preparation. Action potentials
from 1 endocardial and 2 epicardial sites (Epi1
and Epi2) were recorded
simultaneously, together with a transmural ECG. Under
control conditions, a prominent notch in epicardium but not endocardium
gives rise to a prominent J wave in the ECG (Figure 1A). We used
the potassium channel opener pinacidil (3 µmol/L) to produce an
outward shift in the balance of current. Pinacidil caused an
all-or-none repolarization of the AP at the end of phase 1, leading to
loss of the AP dome and marked abbreviation of the action potential
duration (APD) (Figure 1B). The resultant transmural voltage
gradient caused an ST-segment elevation in the ECG. A premature beat
introduced at an S1-S2
interval of 310 ms led to partial recovery of the AP plateau at
Epi2, thus slightly reducing the degree of
ST-segment elevation (Figure 1B, second beat). In the continued
presence of pinacidil, acceleration of the stimulation rate from a
basic cycle length (BCL) of 2000 to 1000 ms for 2 minutes restored the
epicardial AP dome and normalized the ST segment. As will be discussed
later, these effects of prematurity and rate are secondary to a
diminished availability of Ito (Figure 1C).
|
Any agent or agency capable of reducing the magnitude of the epicardial
AP notch, either by direct inhibition of
Ito or by other modification of the balance
of currents active during phases 1 and 2, would be expected to restore
the AP dome and lead to normalization or reduction of the ST-segment
elevation. Figures 2 and 3 illustrate 2 examples. In Figure 2, the addition of pinacidil (2.5 µmol/L) leads to a
gradual loss of epicardial AP dome (middle panel), resulting in a
progressive depression of the plateau and abbreviation of epicardial
APD. Corresponding changes are observed in the ST segment, with
progressive elevation as the transmural voltage gradient increases.
Pinacidil (1 to 5 µmol/L) induced a complete loss of AP dome in
RV epicardium in 
70% (18 of 26) of the preparations. The addition
of 4-aminopyridine (4-AP), an
Ito blocker, to the perfusate
restored the epicardial AP dome and normalized the ST segment (Figure 2, right). Qualitatively similar results were obtained with
quinidine (5 µmol/L, Figure 3, n=6) and
disopyramide (10 µmol/L, not shown, n=4), both of
which have been shown to inhibit
Ito.19 20 The effect of
4-AP, quinidine, and disopyramide on the magnitude of phase
1 (AP peak to end of phase 1) of the RV epicardial AP is summarized in
the Table. 4-AP was most potent and
disopyramide least potent. Washout of the drug readily
reversed the effects of pinacidil in all cases.
|
|
|
The influence of the autonomic nervous system on ST-segment elevation
in patients with Brugada syndrome is well established.2 3
An increase in vagal activity is known to cause an ST-segment elevation
in the right precordial leads (V1 through
V3), whereas sympathetic agonists normalize the
ST segment. In the wedge, acetylcholine (ACh, 1 to 5 µmol/L)
depressed the AP plateau in RV epicardium but not endocardium in 3 of 5
preparations, leading to an ST-segment elevation (Figure 4) that was readily reversed with
atropine (1 µmol/L, not shown). ACh alone did not lead to loss
of the AP dome in RV epicardium, but it facilitated loss of the dome in
the presence of pinacidil or flecainide (Figure 5). Similar results were obtained in 4
other experiments. The sympathetic agonist isoproterenol (0.1 to 1
µmol/L) normalized the ST segment by restoring the epicardial AP dome
in 5 of 5 experiments (eg, see Figure 5D).
|
|
Mechanism Underlying Ventricular Arrhythmias in
the Brugada Syndrome: Role of Phase 2 Reentry
In isolated tissues, loss of the dome occurs at some RV epicardial
sites but not others, resulting in a marked dispersion of
repolarization that underlies the development of local reexcitation via
a mechanism called phase 2 reentry.9 11 14 16 Similar
electrical heterogeneity is observed in the wedge
(Figure 6). Figure 6A shows the
effect of pinacidil (2.5 µmol/L) to cause loss of the AP dome at
some sites (Epi1) but not others
(Epi2), resulting in marked dispersion of
repolarization on the epicardial surface. Dispersion was more
pronounced during the plateau phase of the AP, as reflected by a
greater epicardial dispersion of repolarization time at
APD50 versus APD90. 4-AP
(2 mmol/L, Figure 6A, right) restored the dome and greatly
diminished dispersion of repolarization. Summary data are shown in
Figure 6B.
|
Using isolated epicardial sheets, we previously demonstrated that loss
of the epicardial AP dome at some sites but not others generates large
voltage gradients between the epicardial sites at which the dome is
maintained and those at which it is lost and that these electrotonic
forces can produce an extrasystole via local reexcitation (phase 2
reentry), which in turn can initiate circus movement
reentry.16 In the present study, we induced
ventricular arrhythmias via phase 2 reentry in 19
of 28 arterially perfused RV wedge preparations by exposure
of the preparations to pinacidil, cold, local pressure on the
epicardial surface, a Ca2+ channel blocker
(CdCl), or a combination of ACh and pinacidil (Figures 7 and 8).
We did not study the effects of cold and pressure on phase 2 reentry
systemically. In our experiments, the RV wedge is cannulated in cold
Tyrode's solution and then transported to a warm bath. During the
warming period, phase 2 reentry–induced ventricular
arrhythmias were observed in 5 preparations. The
arrhythmias disappeared at higher temperatures (>33°C). The
process was reversible, ie, reducing temperature resulted in
reappearance of phase 2 reentry–induced VT/VF. In 2 preparations,
local pressure caused loss of the AP dome at the contact site on the
epicardial surface, leading to phase 2 reentry. Release of pressure
abolished the arrhythmias. Local pressure on endocardium or the
M region failed to induce phase 2 reentry (n=2). Phase 2
reentry–induced VT/VF was observed in 2 of 5 preparations exposed to
Ca2+ channel block and 12 of 18 preparations
exposed to pinacidil. The arrhythmias generally appeared within
30 minutes after each intervention. The loss of the AP dome and
development of phase 2 reentry were largely dependent on the initial
magnitude of the Ito-mediated AP notch in
epicardium. The phase 1 magnitude was 39.9±7.7 mV (n=19) in the group
that developed phase 2 reentry versus 29.1±4.6 mV (P<0.05)
in the group that failed to develop phase 2 reentry.
|
|
Figure 7
illustrates an example of phase 2 reentry–induced VF
developing after exposure of RV epicardium to pinacidil (10
µmol/L). Loss of the AP dome at some epicardial sites caused an
ST-segment elevation similar to that observed in patients with the
Brugada syndrome. Propagation of the dome from sites at which it is
maintained to those at which it is lost gives rise to an extrasystole
via phase 2 reentry (first grouping). In the second grouping, phase 2
reentry generates an extrasystole with a slightly longer coupling
interval, which succeeds in precipitating VF. Thus,
heterogeneous loss of the AP dome leads to phase 2 reentry,
thus providing a closely coupled extrasystole, which in turn triggers
VF. 4-AP (2 mmol/L, Figure 8A), quinidine (5 µmol/L,
Figure 8B), and disopyramide (10 µmol/L, data
not shown) restored homogeneity by restoring the epicardial AP dome at
sites at which it was abolished, thus terminating all arrhythmic
activity.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
ST-Segment Elevation and Phase 2 Reentry
In the ECG, particularly in the precordial leads, an ST-segment deviation is usually the result of a transmural voltage gradient caused by differences in the level of the AP plateau among cells spanning the ventricular wall. Our findings indicate that loss of the AP dome in RV epicardium but not endocardium gives rise to a transmural voltage gradient that underlies ST-segment elevation, similar to that observed in the ECG of Brugada syndrome patients. Loss of the dome is critically dependent on the presence of a prominent Ito-mediated phase 1 or spike and dome (notch) morphology of the epicardial AP. Under normal conditions, the presence of an AP notch in epicardium but not endocardium gives rise to a transmural current that is responsible for the inscription of the J wave of the ECG.12 Under pathophysiological conditions, the J wave may become progressively larger (due to accentuation of the AP notch) during the transition to ST-segment elevation (due to loss of the dome) (Figure 5
).
In some species, including dogs, Ito is
relatively slow to recover from inactivation. As a consequence, changes
in rate of prematurity of the impulse can alter the availability of
Ito and thus the ability to abolish the AP
dome (Figure 1). Although reactivation of
Ito is faster in humans than in dogs,
rate-dependent changes in the manifestation of the ST segment have been
reported in some Brugada patients.7 21
Because Ito and the AP notch are much smaller in left ventricular epicardium,11 22 loss of the AP dome and phase 2 reentry are much more difficult to induce. These observations are consistent with the appearance of ST-segment elevation only in the right precordial leads in patients with the Brugada syndrome.
Loss of the AP dome is critically dependent on the balance of currents active during phase 1 of the AP (principally Ito, INa, and ICa). Any agent capable of causing an outward shift in the current active at the end of phase 1 of RV epicardium (eg, increase in IK-ATP and/or IK-ACh and decrease in ICa and INa) can contribute to loss of the AP dome. These include K+ channel openers such as pinacidil, Ca2+ channel blockers such as CdCl, sodium channel blockers such as flecainide, and parasympathetic agonists such as ACh. All of these agents are shown to facilitate loss of the dome in RV epicardium in the wedge preparation.
Although we demonstrated this phenomenon using 6 very different methods to alter the balance of current at the end of phase 1, we chose to focus on the ability of pinacidil to mimic the Brugada syndrome because the data obtained most likely apply to other syndromes involving ST-segment elevation, particularly acute ischemia. It is important to recognize that the fundamental mechanism underlying arrhythmogenesis under these conditions is similar regardless of the specific current altered.
Sodium and calcium channel block facilitates all-or-none repolarization
by leaving the strong Ito in RV epicardium
less opposed, resulting in termination of phase 1 at more negative
potentials, at which the availability of
ICa may be reduced. The class IC
antiarrhythmic agents, including flecainide, are especially effective
in causing loss of the APD dome because of their slow dissociation from
the sodium channel. This feature of the drug gives rise to strong
use-dependent block of the channel, thus causing profound
INa inhibition at relatively slow rates at
which Ito has had sufficient time to
reactivate. Once again, the availability of
Ito is pivotal. It is noteworthy that our
data fail to demonstrate an important effect of flecainide to inhibit
Ito at the concentration used. The
combination of sodium channel block and ACh (Figure 5) is
synergistic in that loss of the AP dome occurs via a reduction in both
INa and ICa as
well as augmentation of IK-ACh. These
findings parallel 2 additional very important features of the Brugada
syndrome: (1) vagally induced ST-segment elevation and (2) sodium
channel block unmasking of the
syndrome.5 6 8 23 24
The first demonstration of phase 2 reentry accompanying loss of the AP dome involved the use of high concentrations of flecainide to block the sodium channels.14 The sodium channel thus became a primary gene candidate for the Brugada syndrome. Either a decrease in the density or an acceleration of inactivation of the sodium channel would leave Ito unopposed during the early phases of the AP. In addition to the sodium channel gene SCN5A, other candidates include gene mutations that alter the intensity or kinetics of either Ito or ICa, ICl(Ca), IK-ATP, or autonomic receptors.
The only gene thus far linked to the Brugada syndrome is SCN5A.25 Chen et al25 found several mutations different from those known to contribute to the LQT3 form of the long-QT syndrome. The gene defects caused either an acceleration of the recovery of the sodium channel from inactivation (missense mutation) or nonfunctional sodium channels (frameshift mutation). Other Brugada patients were found not to be linked to SCN5A, suggesting genetic heterogeneity of the disease.
These genetic findings provide support for the hypothesis that the Brugada syndrome is a primary electrical disease and further validate our perfused-wedge model as a surrogate of the clinical syndrome. The SCN5A defect also provides us with an understanding of the basis for conduction disturbances that sometimes accompany the Brugada syndrome26 and why sodium channel blockers, particularly ajmaline and flecainide, are so effective in unmasking the syndrome in the clinic.5 6 8 23 24 27 28
Isoproterenol, through its actions to increase ICa, is especially effective in restoring the AP dome in the wedge. This finding parallels the clinical observation that ST-segment elevation in patients with the Brugada syndrome is reduced or totally normalized after ß-adrenergic agonists.2 29
Because Ito plays a pivotal role in this mechanism, it is not surprising that agents that block this current are also capable of restoring the AP dome, normalizing the ST segment, and preventing arrhythmogenesis. 4-AP and quinidine, and to a lesser extent disopyramide, restored the AP dome, normalized the ST segment, and prevented arrhythmias in the wedge. All 3 agents inhibit Ito.19 20 30 The vagolytic effects of the class I antiarrhythmic agents may also contribute to the actions of the drug. Actions of these agents to block IKr and IKs may have contributed to their ability to restore the AP dome, although block of Ito is clearly the predominant effect. However, selective IKr or IKs blockers are not able to restore the epicardial AP dome under similar conditions. Our results, demonstrating a therapeutic effect of quinidine, may explain the success of Belhassan and coworkers31 in treating patients with idiopathic VF.
VT and Fibrillation
Loss of the dome at some epicardial sites but not others creates a
marked dispersion of repolarization within epicardium (Figure 6), leading to local reexcitation via phase 2 reentry.
Transmural dispersion of repolarization, also present under these
conditions, may facilitate the induction of phase 2 reentry and
provides further substrate for the development of VT/VF. It has long
been appreciated that a circus movement reentry underlies most cases of
VT and VF and that an extrasystole is often required to trigger the
arrhythmia. The mechanism we describe in this report not only
provides the substrate for reentry in the form of epicardial and
transmural dispersion of repolarization but also provides its own
extrasystole to trigger the arrhythmia. Extrasystolic
beats generated via phase 2 reentry are generally closely coupled,
falling on the T wave (Figures 7 and 8). This malignant
R-on-T phenomenon is always observed in patients with idiopathic
VF.4 32
The heterogeneous loss of the AP dome in RV epicardium appears to be largely a result of a heterogeneous distribution of Ito along the RV epicardial surface.11 16 22 33 Our data argue against a contribution of heterogeneous distribution of IK-ATP channels, because pinacidil exerts similar effects in the 3 cell types in the presence of Ito blocking concentrations of 4-AP.
Additional Clinical Correlates
The similarity between the ECG manifestation of the Brugada
syndrome and that of acute myocardial infarction suggests that the
mechanism responsible for arrhythmogenesis in patients with the Brugada
syndrome is similar to that responsible for early
ventricular arrhythmias in patients with acute
myocardial infarction. The Brugada model may therefore
represent a stable (ischemia-free) model of the early
phases of ischemia. A test of this hypothesis has been
conducted in isolated epicardial tissues16 22 and is
currently under way in the perfused wedge. This experimental model may
also apply to other mechanisms of arrhythmogenesis associated with
ST-segment elevation.8
|
Acknowledgments |
|---|
This study was supported by grants HL-37396 and HL-47678 from the National Institutes of Health, a Grant-in-Aid from the American Heart Association, the Sixth and Seventh Manhattan Masonic Districts, and the Masons of New York State and Florida. We gratefully acknowledge the expert technical assistance of Judy Hefferon, Tengxian Liu, Di Hou, and Robert Goodrow.
Received December 8, 1998; revision received June 1, 1999; accepted June 9, 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol. 1992;20:1391–1396.[Abstract]
2. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol. 1996;27:1061–1070.[Abstract]
3.
Kasanuki H, Ohnishi S, Ohtuka M, Matsuda N, Nirei T,
Isogai R, Shoda M, Toyoshima Y, Hosoda S. Idiopathic
ventricular fibrillation induced with vagal activity in
patients without obvious heart disease. Circulation. 1997;95:2277–2285.
4. Nademanee K. Sudden unexplained death syndrome in southeast Asia. Am J Cardiol. 1997;79:10–11.[Medline] [Order article via Infotrieve]
5.
Brugada J, Brugada R, Brugada P. Right bundle-branch
block and ST-segment elevation in leads V1
through V3: a marker for sudden death in patients
without demonstrable structural heart disease. Circulation. 1998;97:457–460.
6. Brugada J, Brugada P. Further characterization of the syndrome of right bundle branch block, ST segment elevation, and sudden cardiac death. J Cardiovasc Electrophysiol. 1997;8:325–331.[Medline] [Order article via Infotrieve]
7. Antzelevitch C. The Brugada syndrome. J Cardiovasc Electrophysiol. 1998;9:513–516.[Medline] [Order article via Infotrieve]
8.
Gussak I, Antzelevitch C, Bjerregaard P, Towbin JA,
Chaitman BR. The Brugada syndrome: clinical,
electrophysiological and genetic aspects.
J Am Coll Cardiol. 1999;33:5–15.
9. Antzelevitch C, Brugada P, Brugada J, Brugada R, Nademanee K, Towbin JA. The Brugada Syndrome. Armonk, NY: Futura Publishing Co: 1999:1–99.
10.
Litovsky SH, Antzelevitch C. Transient outward current
prominent in canine ventricular epicardium but not
endocardium. Circ Res. 1988;62:116–126.
11.
Di Diego JM, Sun ZQ, Antzelevitch C.
Ito and action potential notch are smaller in
left vs. right canine ventricular epicardium. Am
J Physiol. 1996;271:H548–H561.
12.
Yan GX, Antzelevitch C. Cellular basis for the
electrocardiographic J wave. Circulation. 1996;93:372–379.
13.
Di Diego JM, Antzelevitch C. Pinacidil-induced
electrical heterogeneity and extrasystolic
activity in canine ventricular tissues: does activation of
ATP-regulated potassium current promote phase 2 reentry?
Circulation. 1993;88:1177–1189.
14.
Krishnan SC, Antzelevitch C. Flecainide-induced
arrhythmia in canine ventricular epicardium: phase
2 reentry? Circulation. 1993;87:562–572.
15.
Di Diego JM, Antzelevitch C. High
[Ca2+]-induced electrical
heterogeneity and extrasystolic activity in
isolated canine ventricular epicardium: phase 2 reentry.
Circulation. 1994;89:1839–1850.
16. Lukas A, Antzelevitch C. Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia: the antiarrhythmic effects of 4-aminopyridine. Cardiovasc Res. 1996;32:593–603.[Medline] [Order article via Infotrieve]
17.
Yan GX, Shimizu W, Antzelevitch C. Characteristics and
distribution of M cells in arterially-perfused canine left
ventricular wedge preparations. Circulation. 1998;98:1921–1927.
18.
Yan GX, Antzelevitch C. Cellular basis for the normal T
wave and the electrocardiographic manifestations of the long QT
syndrome. Circulation. 1998;98:1928–1936.
19.
Imaizumi Y, Giles WR. Quinidine-induced inhibition of
transient outward current in cardiac muscle. Am J
Physiol. 1987;253:H704–H708.
20. Virag L, Varro A, Papp C. Effect of disopyramide on potassium currents in rabbit ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol. 1998;357:268–275.[Medline] [Order article via Infotrieve]
21. Matsuo K, Shimizu W, Kurita T, Inagaki M, Aihara N, Kamakura S. Dynamic changes of 12-lead electrocardiograms in a patient with Brugada syndrome. J Cardiovasc Electrophysiol. 1998;9:508–512.[Medline] [Order article via Infotrieve]
22.
Lukas A, Antzelevitch C. Differences in the
electrophysiological response of canine
ventricular epicardium and endocardium to ischemia:
role of the transient outward current. Circulation. 1993;88:2903–2915.
23. Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol. 1998;9:1167–1172.[Medline] [Order article via Infotrieve]
24. Nakamura F, Segawa K, Ito H, Tanaka S, Yoshimoto N. Class Ic antiarrhythmic drugs, flecainide and pilsicainide, produce ST segment elevation simulating inferior myocardial ischemia. J Cardiovasc Electrophysiol. 1998;9:855–858.[Medline] [Order article via Infotrieve]
25. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potreau D, Moya A, Borggrefe M, Breithardt G, Ortiz M, Wang Z, Antzelevitch C, O'Brien RE, Schultz-Bahr E, Keating MT, Towbin JA, Wang Q. Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature. 1997;392:293–296.
26. Matsuo K, Shimizu W, Kurita T, Suyama K, Aihara N, Kamakura S, Shimomura K. Increased dispersion of repolarization time determined by monophasic action potentials in two patients with familial idiopathic ventricular fibrillation. J Cardiovasc Electrophysiol. 1998;9:74–83.[Medline] [Order article via Infotrieve]
27. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, Ogawa S. Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome. J Am Coll Cardiol. 1996;27:1061–1070.
28. Chinushi M, Aizawa Y, Ogawa Y, Shiba M, Takahashi K. Discrepant drug action of disopyramide on ECG abnormalities and induction of ventricular arrhythmias in a patient with Brugada syndrome. J Electrocardiol. 1997;30:133–136.[Medline] [Order article via Infotrieve]
29.
Viskin S, Belhassen B. Increased vagal activity in
idiopathic VF. Circulation. 1998;97:937–940. Letter and
response.
30.
Yatani A, Wakamori M, Mikala G, Bahinski A. Block of
transient outward-type cloned cardiac K+ channel
currents by quinidine. Circ Res. 1993;73:351–359.
31.
Belhassen B, Shapira I, Shoshani D, Paredes A, Miller
H, Laniado S. Idiopathic ventricular fibrillation:
inducibility and beneficial effects of class I antiarrhythmic agents.
Circulation. 1987;75:809–816.
32. Viskin S, Lesh MD, Eldar M, Fish R, Setbon I, Laniado S, Belhassen B. Mode of onset of malignant ventricular arrhythmias in idiopathic ventricular fibrillation. J Cardiovasc Electrophysiol. 1997;8:1115–1120.[Medline] [Order article via Infotrieve]
33. Lukas A. Electrophysiology of myocardial cells in the epicardial, midmyocardial and endocardial layers of the ventricle. J Cardiovasc Pharmacol Ther. 1997;2:61–72.
This article has been cited by other articles:
 |
|
 |
|
  C. Veltmann, C. Wolpert, F. Sacher, P. Mabo, R. Schimpf, F. Streitner, J. Brade, F. Kyndt, J. Kuschyk, H. Le Marec, et al. Response to intravenous ajmaline: a retrospective analysis of 677 ajmaline challenges Europace, July 9, 2009; (2009) eup189v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Calloe, J. M. Cordeiro, J. M. Di Diego, R. S. Hansen, M. Grunnet, S. P. Olesen, and C. Antzelevitch A transient outward potassium current activator recapitulates the electrocardiographic manifestations of Brugada syndrome Cardiovasc Res, March 1, 2009; 81(4): 686 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gaborit, T. Wichter, A. Varro, V. Szuts, G. Lamirault, L. Eckardt, M. Paul, G. Breithardt, E. Schulze-Bahr, D. Escande, et al. Transcriptional profiling of ion channel genes in Brugada syndrome and other right ventricular arrhythmogenic diseases Eur. Heart J., February 2, 2009; 30(4): 487 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morita, K. F. Kusano, D. Miura, S. Nagase, K. Nakamura, S. T. Morita, T. Ohe, D. P. Zipes, and J. Wu Fragmented QRS as a Marker of Conduction Abnormality and a Predictor of Prognosis of Brugada Syndrome Circulation, October 21, 2008; 118(17): 1697 - 1704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nagase, K. F. Kusano, H. Morita, and T. Ohe Reply J. Am. Coll. Cardiol., August 19, 2008; 52(8): 674 - 675. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Delpon, J. M. Cordeiro, L. Nunez, P. E. B. Thomsen, A. Guerchicoff, G. D. Pollevick, Y. Wu, J. K. Kanters, C. T. Larsen, E. Burashnikov, et al. Functional Effects of KCNE3 Mutation and Its Role in the Development of Brugada Syndrome Circ Arrhythmia Electrophysiol, August 1, 2008; 1(3): 209 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Babaee Bigi, A. Aslani, and A. Aslani Significance of cardiac autonomic neuropathy in risk stratification of Brugada syndrome Europace, July 1, 2008; 10(7): 821 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Cordeiro, M. Mazza, R. Goodrow, N. Ulahannan, C. Antzelevitch, and J. M. Di Diego Functionally distinct sodium channels in ventricular epicardial and endocardial cells contribute to a greater sensitivity of the epicardium to electrical depression Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H154 - H162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Petitprez, T. Jespersen, E. Pruvot, D. I. Keller, C. Corbaz, J. Schlapfer, H. Abriel, and J. P. Kucera Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome Cardiovasc Res, June 1, 2008; 78(3): 494 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Aizawa, M. Chinushi, M. Tagawa, H. Furushima, S. Okada, K. Iijima, D. Izumi, H. Watanabe, and S. Komura A Post-QRS Potential in Brugada Syndrome: Its Relation to Electrocardiographic Pattern and Possible Genesis J. Am. Coll. Cardiol., April 29, 2008; 51(17): 1720 - 1721. [Full Text] [PDF]
|
|
|
|
|
|
S. Nagase, K. F. Kusano, H. Morita, N. Nishii, K. Banba, A. Watanabe, S. Hiramatsu, K. Nakamura, S. Sakuragi, and T. Ohe Longer Repolarization in the Epicardium at the Right Ventricular Outflow Tract Causes Type 1 Electrocardiogram in Patients With Brugada Syndrome J. Am. Coll. Cardiol., March 25, 2008; 51(12): 1154 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hayashi, S. Takatsuki, P. Maison-Blanche, A. Messali, A. Haggui, P. Milliez, A. Leenhardt, and F. Extramiana Ventricular Repolarization Restitution Properties in Patients Exhibiting Type 1 Brugada Electrocardiogram With and Without Inducible Ventricular Fibrillation J. Am. Coll. Cardiol., March 25, 2008; 51(12): 1162 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-S. Chen and S. G. Priori The Brugada Syndrome J. Am. Coll. Cardiol., March 25, 2008; 51(12): 1176 - 1180. [Full Text] [PDF]
|
|
|
|
|
|
T. Ueyama, A. Shimizu, M. Esato, Y. Yoshiga, A. Sawa, S. Suzuki, N. Sugi, and M. Matsuzaki Pilsicainide-induced Brugada-type ECG and ventricular arrhythmias originating from the left posterior fascicle in a case with Brugada syndrome associated with idiopathic left ventricular tachycardia Europace, January 1, 2008; 10(1): 86 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Six, J.-S. Hermida, H. Huang, L. Gouas, V. Fressart, N. Benammar, B. Hainque, I. Denjoy, M. Chahine, and P. Guicheney The occurrence of Brugada syndrome and isolated cardiac conductive disease in the same family could be due to a single SCN5A mutation or to the accidental association of both diseases Europace, January 1, 2008; 10(1): 79 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Casini, H. L. Tan, Z. A. Bhuiyan, C. R. Bezzina, P. Barnett, E. Cerbai, A. Mugelli, A. A.M. Wilde, and M. W. Veldkamp Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation Cardiovasc Res, December 1, 2007; 76(3): 418 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. London, M. Michalec, H. Mehdi, X. Zhu, L. Kerchner, S. Sanyal, P. C. Viswanathan, A. E. Pfahnl, L. L. Shang, M. Madhusudanan, et al. Mutation in Glycerol-3-Phosphate Dehydrogenase 1-Like Gene (GPD1-L) Decreases Cardiac Na+ Current and Causes Inherited Arrhythmias Circulation, November 13, 2007; 116(20): 2260 - 2268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Furushima, M. Chinushi, K. Okamura, K. Iijima, S. Komura, Y. Tanabe, S. Okada, D. Izumi, and Y. Aizawa Comparison of conduction delay in the right ventricular outflow tract between Brugada syndrome and right ventricular cardiomyopathy: investigation of signal average ECG in the precordial leads Europace, October 1, 2007; 9(10): 951 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2024 - H2038. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Stokoe, R. Balasubramaniam, C. A. Goddard, W. H. Colledge, A. A. Grace, and C. L.-H. Huang Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/ murine hearts modelling the Brugada syndrome J. Physiol., May 15, 2007; 581(1): 255 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. N. Sabir, M. J. Killeen, C. A. Goddard, G. Thomas, S. Gray, A. A. Grace, and C. L.-H. Huang Transient alterations in transmural repolarization gradients and arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts J. Physiol., May 15, 2007; 581(1): 277 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Viskin Brugada Syndrome in Children: Don't Ask, Don't Tell? Circulation, April 17, 2007; 115(15): 1970 - 1972. [Full Text] [PDF]
|
|
|
|
|
|
A. A. Kondratyev, J. G. C. Ponard, A. Munteanu, S. Rohr, and J. P. Kucera Dynamic changes of cardiac conduction during rapid pacing Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1796 - H1811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Watanabe, K. Fukushima Kusano, H. Morita, D. Miura, W. Sumida, S. Hiramatsu, K. Banba, N. Nishii, S. Nagase, K. Nakamura, et al. Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome Eur. Heart J., July 1, 2006; 27(13): 1579 - 1583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Morita, D. P. Zipes, J. Lopshire, S. T. Morita, and J. Wu T wave alternans in an in vitro canine tissue model of Brugada syndrome Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H421 - H428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Aiba, W. Shimizu, I. Hidaka, K. Uemura, T. Noda, C. Zheng, A. Kamiya, M. Inagaki, M. Sugimachi, and K. Sunagawa Cellular Basis for Trigger and Maintenance of Ventricular Fibrillation in the Brugada Syndrome Model: High-Resolution Optical Mapping Study J. Am. Coll. Cardiol., May 16, 2006; 47(10): 2074 - 2085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sassone, S. Sacca, and M. Donateo Paradoxical effect of ajmaline in a patient with Brugada syndrome. Europace, April 1, 2006; 8(4): 251 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Fish, D. R. Welchons, Y.-S. Kim, S.-H. Lee, W.-K. Ho, and C. Antzelevitch Dimethyl Lithospermate B, an Extract of Danshen, Suppresses Arrhythmogenesis Associated With the Brugada Syndrome Circulation, March 21, 2006; 113(11): 1393 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Sugao, A Fujiki, M Sakabe, K Nishida, T Tsuneda, J Iwamoto, K Mizumaki, and H Inoue New quantitative methods for evaluation of dynamic changes in QT interval on 24 hour Holter ECG recordings: QT interval in idiopathic ventricular fibrillation and long QT syndrome Heart, February 1, 2006; 92(2): 201 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. O. Verkerk, R. Wilders, E. Schulze-Bahr, L. Beekman, Z. A. Bhuiyan, J. Bertrand, L. Eckardt, D. Lin, M. Borggrefe, G. Breithardt, et al. Role of sequence variations in the human ether-a-go-go-related gene (HERG, KCNH2) in the Brugada syndrome Cardiovasc Res, December 1, 2005; 68(3): 441 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Aksay, T Okan, and S Yanturali Brugada syndrome, manifested by propafenone induced ST segment elevation Emerg. Med. J., October 1, 2005; 22(10): 748 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schimpf, C. Wolpert, F. Gaita, C. Giustetto, and M. Borggrefe Short QT syndrome Cardiovasc Res, August 15, 2005; 67(3): 357 - 366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Meregalli, A. A.M. Wilde, and H. L. Tan Pathophysiological mechanisms of Brugada syndrome: Depolarization disorder, repolarization disorder, or more? Cardiovasc Res, August 15, 2005; 67(3): 367 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Brugada, R. Brugada, J. Brugada, S. G. Priori, C. Napolitano, P. Brugada, R. Brugada, J. Brugada, S. G. Priori, and C. Napolitano Should patients with an asymptomatic Brugada electrocardiogram undergo pharmacological and electrophysiological testing? Circulation, July 12, 2005; 112(2): 279 - 292. [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, D. W. Benson, M. Tristani-Firouzi, L. J. Ptacek, R. Tawil, P. J. Schwartz, A. L. George, M. Horie, G. Andelfinger, G. L. Snow, et al. Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations: Characteristic T-U-Wave Patterns Predict the KCNJ2 Genotype Circulation, May 31, 2005; 111(21): 2720 - 2726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch, P. Brugada, M. Borggrefe, J. Brugada, R. Brugada, D. Corrado, I. Gussak, H. LeMarec, K. Nademanee, A. R. Perez Riera, et al. Brugada Syndrome: Report of the Second Consensus Conference: Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association Circulation, February 8, 2005; 111(5): 659 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Clancy and R. S. Kass Inherited and Acquired Vulnerability to Ventricular Arrhythmias: Cardiac Na+ and K+ Channels Physiol Rev, January 1, 2005; 85(1): 33 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Hermida, I. Denjoy, G.èv. Jarry, S. Jandaud, C. Bertrand, and J. Delonca Electrocardiographic predictors of Brugada type response during Na channel blockade challenge Europace, January 1, 2005; 7(5): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Cardiac repolarization. The long and short of it Europace, January 1, 2005; 7(s2): S3 - S9. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zicha, L. Xiao, S. Stafford, T. J. Cha, W. Han, A. Varro, and S. Nattel Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts J. Physiol., December 15, 2004; 561(3): 735 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Extramiana and C. Antzelevitch Amplified Transmural Dispersion of Repolarization as the Basis for Arrhythmogenesis in a Canine Ventricular-Wedge Model of Short-QT Syndrome Circulation, December 14, 2004; 110(24): 3661 - 3666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Maass, A. Ghanem, J.-S. Kim, M. Saathoff, S. Urschel, G. Kirfel, R. Grummer, M. Kretz, T. Lewalter, K. Tiemann, et al. Defective Epidermal Barrier in Neonatal Mice Lacking the C-Terminal Region of Connexin43 Mol. Biol. Cell, October 1, 2004; 15(10): 4597 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Belhassen, A. Glick, and S. Viskin Efficacy of Quinidine in High-Risk Patients With Brugada Syndrome Circulation, September 28, 2004; 110(13): 1731 - 1737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Yan, A. Joshi, D. Guo, T. Hlaing, J. Martin, X. Xu, and P. R. Kowey Phase 2 Reentry as a Trigger to Initiate Ventricular Fibrillation During Early Acute Myocardial Ischemia Circulation, August 31, 2004; 110(9): 1036 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Burashnikov, S. Mannava, and C. Antzelevitch Transmembrane action potential heterogeneity in the canine isolated arterially perfused right atrium: effect of IKr and IKur/Ito block Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2393 - H2400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Hermida, I. Denjoy, J. Clerc, F. Extramiana, G. Jarry, P. Milliez, P. Guicheney, S. Di Fusco, J.-L. Rey, B. Cauchemez, et al. Hydroquinidine therapy in Brugada syndrome J. Am. Coll. Cardiol., May 19, 2004; 43(10): 1853 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. KLEBER and Y. RUDY Basic Mechanisms of Cardiac Impulse Propagation and Associated Arrhythmias Physiol Rev, April 1, 2004; 84(2): 431 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Tukkie, P. Sogaard, J. Vleugels, I. K.L.M. de Groot, A. A.M. Wilde, and H. L. Tan Delay in Right Ventricular Activation Contributes to Brugada Syndrome Circulation, March 16, 2004; 109(10): 1272 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Sanchez and A. M. Kates Brugada-type Electrocardiographic Pattern Unmasked by Fever Mayo Clin. Proc., February 1, 2004; 79(2): 273 - 274. [PDF]
|
|
|
|
|
|
F. G. Akar, R. C. Wu, I. Deschenes, A. A. Armoundas, V. Piacentino III, S. R. Houser, and G. F. Tomaselli Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H602 - H609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kimura, T. Kobayashi, S. Owada, K. Ashikaga, T. Higuma, S. Sasaki, A. Iwasa, S. Motomura, and K. Okumura Mechanism of ST Elevation and Ventricular Arrhythmias in an Experimental Brugada Syndrome Model Circulation, January 6, 2004; 109(1): 125 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wang, R. W. Asinger, and H. J.L. Marriott ST-Segment Elevation in Conditions Other Than Acute Myocardial Infarction N. Engl. J. Med., November 27, 2003; 349(22): 2128 - 2135. [Full Text] [PDF]
|
|
|
|
|
|
H. Morita, S. T. Morita, S. Nagase, K. Banba, N. Nishii, Y. Tani, A. Watanabe, K. Nakamura, K. F. Kusano, T. Emori, et al. Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1624 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Pitzalis, M. Anaclerio, M. Iacoviello, C. Forleo, P. Guida, R. Troccoli, F. Massari, F. Mastropasqua, S. Sorrentino, A. Manghisi, et al. QT-interval prolongation inright precordial leads: an additional electrocardiographic hallmark of Brugada syndrome J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1632 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-X. Yan, R. S. Lankipalli, J. F. Burke, S. Musco, and P. R. Kowey Ventricular repolarization components on the electrocardiogram: Cellular basis and clinical significance J. Am. Coll. Cardiol., August 6, 2003; 42(3): 401 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rolf, H.-J. Bruns, T. Wichter, P. Kirchhof, M. Ribbing, K. Wasmer, M. Paul, G. Breithardt, W. Haverkamp, and L. Eckardt The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol Eur. Heart J., June 2, 2003; 24(12): 1104 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch, P. Brugada, J. Brugada, R. Brugada, J. A. Towbin, and K. Nademanee Brugada syndrome: 1992-2002: A historical perspective J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1665 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Miyoshi, H. Mitamura, K. Fujikura, Y. Fukuda, K. Tanimoto, Y. Hagiwara, M. Ita, and S. Ogawa A mathematical model of phase 2 reentry: role of L-type Ca current Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1285 - H1294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L Tan, C. R Bezzina, J. P.P Smits, A. O Verkerk, and A. A.M Wilde Genetic control of sodium channel function Cardiovasc Res, March 15, 2003; 57(4): 961 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S Chugh, S. Whitesel, M. Turner, C. T Roberts Jr., and S. R Nagalla Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model Cardiovasc Res, February 1, 2003; 57(2): 477 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Moric, E. Herbert, M. Trusz-Gluza, A. Filipecki, U. Mazurek, and T. Wilczok The implications of genetic mutations in the sodium channel gene (SCN5A) Europace, January 1, 2003; 5(4): 325 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Castro Hevia, F. Dorticos Balea, M. Dorantes Sánchez, R. Zayas Molina, and M. A. Quiñones Pérez Unusual response to the ajmaline test in a patient with Brugada syndrome Europace, January 1, 2003; 5(4): 371 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antzelevitch, P. Brugada, J. Brugada, R. Brugada, W. Shimizu, I. Gussak, and A.R. Perez Riera Brugada Syndrome: A Decade of Progress Circ. Res., December 13, 2002; 91(12): 1114 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Noda, W. Shimizu, A. Taguchi, K. Satomi, K. Suyama, T. Kurita, N. Aihara, and S. Kamakura ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1841 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Di Diego, J. M. Cordeiro, R. J. Goodrow, J. M. Fish, A. C. Zygmunt, G. J. Perez, F. S. Scornik, and C. Antzelevitch Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males Circulation, October 8, 2002; 106(15): 2004 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Bauman and R. J. DiDomenico Cocaine-Induced Channelopathies: Emerging Evidence on the Multiple Mechanisms of Sudden Death Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2002; 7(3): 195 - 202. [Abstract] [PDF]
|
|
|
|
|
|
L. Eckardt, P. Kirchhof, E. Schulze-Bahr, S. Rolf, M. Ribbing, P. Loh, H.-J. Bruns, A. Witte, P. Milberg, M. Borggrefe, et al. Electrophysiologic investigation in Brugada syndrome. Yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats Eur. Heart J., September 1, 2002; 23(17): 1394 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kurita, W. Shimizu, M. Inagaki, K. Suyama, A. Taguchi, K. Satomi, N. Aihara, S. Kamakura, J. Kobayashi, and Y. Kosakai The electrophysiologic mechanism of ST-segment elevation in Brugada syndrome J. Am. Coll. Cardiol., July 17, 2002; 40(2): 330 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nagase, K. F. Kusano, H. Morita, Y. Fujimoto, M. Kakishita, K. Nakamura, T. Emori, H. Matsubara, and T. Ohe Epicardial electrogram of the right ventricular outflow tract in patients with the brugada syndrome: Using the epicardial lead J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1992 - 1995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Late potentials and the Brugada syndrome J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1996 - 1999. [Full Text] [PDF]
|
|
|
|
|
|
M. Kanda, W. Shimizu, K. Matsuo, N. Nagaya, A. Taguchi, K. Suyama, T. Kurita, N. Aihara, and S. Kamakura Electrophysiologic characteristics andimplications of induced ventricular fibrillationin symptomatic patients with brugada syndrome J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1799 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.A.M. Wilde, C.A. Remme, R. Derksen, E.F.D. Wever, and R.N.W. Hauer Brugada syndrome Eur. Heart J., April 2, 2002; 23(8): 675 - 676. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Vatta, R. Dumaine, G. Varghese, T. A. Richard, W. Shimizu, N. Aihara, K. Nademanee, R. Brugada, J. Brugada, G. Veerakul, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome Hum. Mol. Genet., February 1, 2002; 11(3): 337 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Brugada, R. Brugada, C. Antzelevitch, J. Towbin, K. Nademanee, and P. Brugada Long-Term Follow-Up of Individuals With the Electrocardiographic Pattern of Right Bundle-Branch Block and ST-Segment Elevation in Precordial Leads V1 to V3 Circulation, January 1, 2002; 105(1): 73 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Viswanathan, C. R. Bezzina, A. L. George Jr., D. M. Roden, A. A.M. Wilde, and J. R. Balser Gating-Dependent Mechanisms for Flecainide Action in SCN5A-Linked Arrhythmia Syndromes Circulation, September 4, 2001; 104(10): 1200 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antzelevitch Heterogeneity of cellular repolarization in LQTS: the role of M cells Eur. Heart J. Suppl., September 1, 2001; 3(suppl_K): K2 - K16. [Abstract] [PDF]
|
|
|
|
|
|
A. C. Zygmunt, G. T. Eddlestone, G. P. Thomas, V. V. Nesterenko, and C. Antzelevitch Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H689 - H697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Transmural dispersion of repolarization and the T wave Cardiovasc Res, June 1, 2001; 50(3): 426 - 431. [Full Text] [PDF]
|
|
|
|
|
|
T. Ikeda, H. Sakurada, K. Sakabe, T. Sakata, M. Takami, N. Tezuka, T. Nakae, M. Noro, Y. Enjoji, T. Tejima, et al. Assessment of noninvasive markers in identifying patients at risk in the brugada syndrome: insight into risk stratification J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1628 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Antzelevitch The Brugada syndrome: diagnostic criteria and cellular mechanisms Eur. Heart J., March 1, 2001; 22(5): 356 - 363. [PDF]
|
|
|
|
|
|
D. Corrado, C. Basso, G. Buja, A. Nava, L. Rossi, and G. Thiene Right Bundle Branch Block, Right Precordial ST-Segment Elevation, and Sudden Death in Young People Circulation, February 6, 2001; 103(5): 710 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R Bezzina, M. B Rook, and A. A.M Wilde Cardiac sodium channel and inherited arrhythmia syndromes Cardiovasc Res, February 1, 2001; 49(2): 257 - 271. [Full Text] [PDF]
|
|
|
|
|
|
X. Wan, S. Chen, A. Sadeghpour, Q. Wang, and G. E. Kirsch Accelerated inactivation in a mutant Na+ channel associated with idiopathic ventricular fibrillation Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H354 - H360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Antzelevitch Electrical Heterogeneity, Cardiac Arrhythmias, and the Sodium Channel Circ. Res., November 24, 2000; 87(11): 964 - 965. [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Kass and C. Cabo Channel structure and drug-induced cardiac arrhythmias PNAS, October 24, 2000; 97(22): 11683 - 11684. [Full Text] [PDF]
|
|
|
|
|
|
D. W. Wang, N. Makita, A. Kitabatake, J. R. Balser, and A. L. George Jr Enhanced Na+ Channel Intermediate Inactivation in Brugada Syndrome Circ. Res., October 13, 2000; 87 (8): e37 - e43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H. T. Wehrens, H. Abriel, C. Cabo, J. Benhorin, and R. S. Kass Arrhythmogenic Mechanism of an LQT-3 Mutation of the Human Heart Na+ Channel {alpha}-Subunit : A Computational Analysis Circulation, August 1, 2000; 102(5): 584 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Rivolta, H. Abriel, M. Tateyama, H. Liu, M. Memmi, P. Vardas, C. Napolitano, S. G. Priori, and R. S. Kass Inherited Brugada and Long QT-3 Syndrome Mutations of a Single Residue of the Cardiac Sodium Channel Confer Distinct Channel and Clinical Phenotypes J. Biol. Chem., August 10, 2001; 276(33): 30623 - 30630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Baroudi, S. Acharfi, C. Larouche, and M. Chahine Expression and Intracellular Localization of an SCN5A Double Mutant R1232W/T1620M Implicated in Brugada Syndrome Circ. Res., January 11, 2002; 90 (1): e11 - e16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Weiss, M. M. Barmada, T. Nguyen, J. S. Seibel, D. Cavlovich, C. A. Kornblit, A. Angelilli, F. Villanueva, D. M. McNamara, and B. London Clinical and Molecular Heterogeneity in the Brugada Syndrome: A Novel Gene Locus on Chromosome 3 Circulation, February 12, 2002; 105(6): 707 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Clancy and Y. Rudy Na+ Channel Mutation That Causes Both Brugada and Long-QT Syndrome Phenotypes: A Simulation Study of Mechanism Circulation, March 12, 2002; 105(10): 1208 - 1213. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||