(Circulation. 2000;101:2631.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology
From the Department of Medicine, Montreal Heart Institute and University of Montreal (D.L., J.F., Z.W., S.N.), and the Departments of Pharmacology (S.N.), Physiology (K.P., A.S.), and Pathology (P.M.), McGill University, Montreal, Quebec, Canada.
Correspondence to Dr Stanley Nattel, Research Center, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec, Canada, H1T 1C8. E-mail nattel{at}icm.umontreal.ca
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Abstract |
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Background—Congestive heart failure (CHF) is frequently associated with atrial fibrillation (AF), but little is known about the effects of CHF on atrial cellular electrophysiology.
Methods and Results—We studied action potential (AP) properties
and ionic currents in atrial myocytes from dogs with CHF induced by
ventricular pacing at 220 to 240 bpm for 5 weeks. Atrial
myocytes from CHF dogs were hypertrophied (mean±SEM capacitance, 89±2
pF versus 71±2 pF in control, n=160 cells per group,
P<0.001). CHF significantly reduced the density of
L-type Ca2+ current (ICa) by
30%, of transient outward K+ current
(Ito) by 50%, and of slow delayed
rectifier current (IKs) by 30% without
altering their voltage dependencies or kinetics. The inward rectifier,
ultrarapid and rapid delayed rectifier, and T-type Ca2+
currents were not altered by CHF. CHF increased transient inward
Na+/Ca2+ exchanger (NCX) current by 45%.
The AP duration of atrial myocytes was not altered by CHF at slow rates
but was increased at faster rates, paralleling in vivo refractory
changes. CHF created a substrate for AF, prolonging mean AF duration
from 8±4 to 535±82 seconds (P<0.01).
Conclusions—Experimental CHF selectively decreases atrial Ito, ICa, and IKs, increases NCX current, and leaves other currents unchanged. The cellular electrophysiological remodeling caused by CHF is quite distinct from that caused by atrial tachycardia, highlighting important differences in the cellular milieu characterizing different clinically relevant AF substrates.
Key Words: ion channels • biophysics • electrophysiology
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Introduction |
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Congestive heart failure (CHF) is a common cause of clinical atrial fibrillation (AF),1 but how it causes the arrhythmia is unclear. Atrial diseases associated with increased atrial pressure are accompanied by abnormal action potential (AP) properties in humans.2 Data regarding the effects of CHF on atrial ionic currents are limited. Atrial myocytes from hearts with terminal failure showed decreased L-type Ca2+ current (ICa) compared with relatively normal hearts.3 Koumi et al4 noted reduced atrial inward rectifier current (IK1) in patients with CHF; however, Le Grand et al5 found no change in IK1 in dilated human atria, whereas ICa and transient outward K+ current (Ito) were reduced. These data are limited by a wide range of heart diseases and variable drug therapy. Many patients also had AF, which can directly alter atrial ionic properties.6 7 Thus, it is difficult to separate CHF-induced ionic abnormalities in patients from those caused by underlying heart disease, concomitant drug therapy, or AF. Rapid ventricular pacing has been used to study experimental CHF-induced ventricular ionic current changes8 9 ; however, the ionic changes caused by experimental CHF at the atrial level are unknown and were the object of the present study.
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Methods |
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Preparation of Animal Model
To produce CHF, the right ventricle was stimulated at 240 bpm for 3 weeks, followed by 2 weeks at 220 bpm. On study days, dogs were anesthetized with morphine (2 mg/kg SC) and
-chloralose (120
mg/kg IV load, 29.25 mg · kg-1 ·
h-1 infusion), and a median sternotomy was
performed. Right atrial (RA) appendage effective refractory period
(ERP) was measured with 15 basic (S1) stimuli,
followed by a premature (S2) stimulus applied
with 5-ms decrements (ERP=longest
S1S2 failing to capture,
mean of 3 determinations). S1 and
S2 were twice-threshold, 2-ms pulses. AF was
induced 10 times by burst pacing (10-Hz, 2-ms pulses, 4x threshold
currents), and mean duration was noted. If persistent AF requiring
cardioversion occurred on 2 occasions, further AF inductions were not
performed. Hearts were excised and atrial cells isolated from RA
pectinate muscles as previously described.10 In vivo
studies were performed in the first 8 control and 18 CHF dogs. Because
performing both in vivo and in vitro studies in each dog greatly
prolonged the experiments, subsequent dogs were used for in vitro study
only, after it had been verified that in vitro results were similar
whether or not they were preceded by in vivo study.
Cellular Electrophysiology
Cells were isolated from 28 control and 28 CHF dogs. Cells in a
1-mL bath were superfused (3 mL/min, 35°C, or for the ultrarapid
delayed rectifier potassium current
[IKur,d], room
temperature11 ). The standard pipette solution
contained (in mmol/L) potassium aspartate 110, KCl 20,
MgCl2 1, GTP 0.1, magnesium ATP 5, sodium
phosphocreatine 5, EGTA 10, and HEPES 10. For AP recording, the
EGTA concentration was decreased to 50 µmol/L. For
ICa recording,
K+ was replaced by Cs+. The
standard extracellular solution contained (in mmol/L) NaCl 136,
KCl 5.4, CaCl2 2, MgCl2
0.8, NaH2PO4 0.33, dextrose
10, and HEPES 10. For ICa
recording, tetraethylammonium
chloride and CsCl replaced NaCl and KCl, respectively. For
K+ current measurement,
CdCl2 (200 µmol/L) or (for studies of
IK) 5 µmol/L nifedipine
was added to block ICa and
ICl,Ca. When a holding potential (HP)
negative to -50 mV was used in studies of K+
currents, Tris-HCl replaced NaCl. The storage solution contained
(in mmol/L) KCl 20,
KH2PO4 10, glutamic acid
70, ß-hydroxybutyric acid 10, taurine 10, EGTA 10, and dextrose 10,
plus albumin 1% (pH adjusted to 7.4 with KOH or with CsOH for
K+-free solutions). For
IK studies, 2 mmol/L
4-aminopyridine was used to block
Ito and IKur,d.
Ito was studied in the presence of 10
mmol/L tetraethylammonium and 1
µmol/L dofetilide to inhibit IKur,d and
IKr, respectively.
IK1 was quantified as 0.5 mmol/L
Ba2+-sensitive currents at the end of 300-ms
pulses from -40 mV.
For Na+/Ca2+ exchanger (NCX) current recording, the extracellular solution contained (in mmol/L) NaCl 140, CaCl2 1, MgCl2 1, dextrose 10, and HEPES 10, plus niflumic acid 50 µmol/L. The EGTA-free pipette solution contained (in mmol/L) CsCl 130, NaCl 5, Mg-ATP 4, and HEPES 10. NCX current was activated as previously described12 by repolarization of the cell to various potentials after 5-ms depolarizing pulses to +20 mV from an HP of -70 mV.
Tight-seal patch-clamp was used to record currents (voltage-clamp
mode) and APs (current-clamp mode). Electrode resistances were 1 to 2
M
for current recording and 3 to 5 M for AP
recording. Cells with normal resting potentials (negative to
-70 mV) were selected for AP recording after it had been
verified that resting potential was not altered by CHF. APs (elicited
by 2-ms twice-threshold pulses) were analyzed at steady state
at each frequency. Recordings were low-pass–filtered at half
the sampling frequency (2 kHz for IKr and
slow delayed rectifier current [IKs] and
10 kHz for APs, ICa,
Ito, and
IKur,d).
Junction potentials (6 to 10 mV) were corrected for AP
recordings only. Seal resistance averaged 8.6±1.2 G. Series
resistance and capacitive time constant averaged 7.6±0.3 M and
506±13 µs before and 1.6±0.04 M and 122.4±6.2 µs after
compensation, respectively. The mean maximum series resistance voltage
drop was 3 mV. Similar numbers of cells from each heart were studied
with each protocol. Cell capacitance (the time integral of capacitance
current divided by the voltage drop during 5-mV steps) was increased in
CHF cells (89.2±1.9 versus 70.5±1.5 pA/pF in control, n=160 each,
P<0.001), so currents are presented in terms of
densities.
Western Blot Analysis of NCX Expression
Western blot analysis of NCX expression has been used to
evaluate ventricular NCX changes in CHF.13 To
evaluate NCX protein expression, fast-frozen left atrial samples were
placed on ice in radioimmunoprecipitation (RIPA) buffer containing
Igepal 1%, sodium deoxycholate 0.5%, SDS 0.1%, ß-mercaptoethanol
10 mmol/L, sodium orthovanadate 100 mmol/L, aprotinin 1
µg/mL, leupeptin 1 µg/mL, pepstatin 1 µg/mL, and PMSF 1
mmol/L in PBS. Samples were then minced and incubated/rotated (1 hour,
4°C). The homogenate was then centrifuged at
4°C and the supernatant stored at -70°C. Protein concentrations
were measured by Bradford assay.
Solubilized membrane proteins were fractionated on 7.5% SDS-polyacrylamide gels at 200 V for 60 minutes, then transferred electrophoretically to Immobilon-P PVDF membranes (Millipore) in 25 mmol/L Tris base, 192 mmol/L glycine, and 5% methanol (18 hours, 0.07 A). Membranes were blocked with 5% nonfat dry milk (NFDM) in TBS (Tris-HCl 50 mmol/L, NaCl 500 mmol/L; pH 7.5) containing 0.05% Tween-20 (TTBS) (2 hours, room temperature), and then incubated overnight (4°C) with NCX antibody (Research Diagnostics; 1:1000 in TTBS with 1% NFDM). Membranes were then washed 3 times in TTBS and reblocked in 1% NFDM/TTBS for 10 minutes, followed by incubation with peroxidase-conjugated goat anti-mouse IgM (1:6000) in 5% NFDM/TTBS (30 minutes) and 3 TTBS washes. Antibody was detected with Western blot Chemiluminescence Reagent Plus (NEN Life Science Products). Band density was quantified with Quantity One software (PDI) incorporating background subtraction algorithms. Total NCX density was calculated as the sum of the densities of each of the 3 isoforms.14
Statistical Analysis
Group data are presented as mean±SEM. Nonlinear curve
fitting was performed with Clampfit in pCLAMP6 (Chebyshev algorithm).
Nonpaired t tests (2-tailed) were used for statistical
comparisons between control and CHF cells.
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Results |
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In Vivo and AP Findings
All dogs with CHF had increased RA (12±1 versus 3.0±0.3 mm Hg, P<0.01) and left ventricular (19±1 versus 2±1 mm Hg, P<0.01) diastolic pressures, evident ascites and pulmonary congestion, and increased respiratory rates (56±2 versus 24±1 breaths per minute, P<0.001). Atrial rates in CHF dogs averaged 139±5 bpm with and 138±4 bpm without ventricular pacing, versus 138±6 bpm in controls. Mean AF duration was 8±4 seconds in controls, versus 535±82 seconds in CHF dogs (P<0.01), with persistent AF (>30 minutes, requiring electrical cardioversion for termination) in 0 of 8 controls versus 10 of 18 CHF dogs.
Resting potential averaged -74.0±0.9 and -72.4±0.4 mV in 20
control and 20 CHF myocytes used for AP analysis, respectively
(P=NS). AP amplitude (1 Hz) averaged 118.8±4.1 mV in
control and 116.0±3.8 mV in CHF myocytes (P=NS). CHF
prolonged AP duration (APD) increasingly as frequency increased (Figure 1
). APDs in isolated cells paralleled
ERP in vivo (eg, at 3 Hz, APD90=138±4 ms in
controls and 145±6 ms in CHF; ERP=131±8 ms in controls and 149±7 ms
in CHF; at 6 Hz, APD90=97±3 ms in controls and
117±6 ms in CHF; ERP=93±4 ms in controls and 122±7 ms in CHF). We
did not observe delayed afterdepolarizations (DADs) during AP
recording.
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Changes in K+ Currents
Ito was decreased by CHF (Figure 2A through 2C). CHF did not alter the
form of the I-V relation (Figure 2D) or voltage dependence
(Figure 2E) or the kinetics (Figure 2F) of
Ito activation and inactivation.
Ito reactivation (Figure 2G) was
monoexponential (time constants for control versus CHF
were 28.1±0.3 versus 30.1±0.5 ms at -70 mV, 59.6±8.5 versus
65.3±2.4 ms at -60 mV, and 88.9±9.3 versus 93.4±11.9 ms at -50 mV;
n=7 per group, P=NS) and, along with frequency dependence
(Figure 2H), was unaffected by CHF.
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act, third-order monoexponential fits)
of data obtained with protocol in A (n=10 per group). G, Recovery time
course of Ito determined with 150-ms paired
pulses and protocol shown (n=10 per group). CHF did not affect
Ito recovery at -80, -70, or -50 mV. H,
Steady-state Ito normalized to
Ito for first pulse at frequencies shown
(n=10 per group).
To study IK, currents were
recorded as shown in Figure 3 10
minutes after membrane rupture and then again at least twice at
10-minute intervals to exclude cells with >10% rundown over 20
minutes. Dofetilide (1 µmol/L) was then added to block
IKr. The drug-resistant component
(IKs, Figure 3A and 3B) was reduced
by CHF. CHF reduced both step (Figure 3C) and tail (Figure 3D) current densities by 30%. The voltage dependence of
IKs activation (tail-current
analysis, Figure 3E) was not altered by CHF (mean
V1/2, +21.3±2.5 mV in CHF and +22.1±2.5 mV in
control; n=15 per group), nor were the kinetics of
IKs activation (Figure 3F).
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Examples of dofetilide-sensitive IKr in
control and CHF cells are shown in Figure 4A and 4B.
IKr density (Figure 4C) and
activation voltage dependence (Figure 4D) were not changed by
CHF. Neither IK1 nor
IKur,d were altered by CHF, as shown in
Figure 5.
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Changes in Ca2+ Currents
Typical L-type ICa recordings
in control and CHF cells are shown in Figure 6A and 6B.
ICa density decreased significantly (Figure 6C) in CHF myocytes (eg, from -16.6±1.4 to -11.5±0.1 pA/pF
at +10 mV, n=35 cells each, P<0.01), without any alteration
in the form of the I-V curve (Figure 6D). CHF did not alter the
voltage dependence of ICa inactivation or
activation (Figure 6E). The time course of
ICa inactivation was biexponential and
voltage dependent but was not altered by CHF (Figure 6F).
ICa recovery was similar in CHF and normal
myocytes (Figure 6G), with monoexponential time
constants averaging 28.6±1.5 and 30.9±3.5 ms for control and CHF,
respectively. CHF similarly did not alter
ICa frequency dependence (Figure 6H).
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T-type ICa was separated from L-type by
subtraction of currents recorded at an HP of -50 mV from those at
-90 mV, as illustrated in Figure 7A and 7B. ICa,T was present in 40% of atrial
myocytes (20 of 50 for both control and CHF). As shown in Figure 7C and 7D, CHF did not alter ICa,T
density.
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NCX Expression
NCX recordings in control and CHF cells are shown in
Figure 8A. Substitution of
Li+ for extracellular
Na+ strongly suppressed inward currents, typical
for the NCX.12 14 CHF substantially increased the density
of NCX current (Figure 8B). For example, at -70 mV (close to
the mean resting potential), NCX averaged -1.1±0.1 in control cells
versus -1.6±0.2 pA/pF in CHF cells (P=0.02). NCX protein
expression was also increased (Figure 8C), by an average of 87%
in atrial tissues from CHF (n=7 blots from 1 heart each) compared with
control dogs (n=4).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In the present study, we found that experimental CHF decreases Ito, L-type ICa, and IKs and increases NCX in atrial myocytes, without altering T-type ICa, IKr, IKl, or IKur,d. The atrial cellular electrophysiological substrate produced by CHF is quite different from that seen with atrial tachycardia–induced remodeling, although both experimental paradigms promote AF.
Comparison With Previous Studies of Cellular Electrophysiology
Associated With Atrial Disease and Arrhythmias
It is well recognized that CHF frequently causes AF in humans.
Alterations in atrial cellular electrophysiology have been reported in
patients2 3 4 5 6 and experimental animals7 15 16 17
with atrial disease and/or dilation. Similar to our observations at
slower rates, APD was not substantially altered in dogs with tricuspid
insufficiency15 and chronic mitral
regurgitation.16 Cats with
endogenous cardiomyopathy had APDs that
were either unchanged or (in more severe cases) increased in the left
atrium.17 Decreases in
Ito5 and
ICa3 5 have been reported
in dilated human atria. IK1 was unchanged
in dilated atria5 but reduced in atria of patients
with symptomatic CHF.4 Both
Ito and the sustained outward current are
reduced in patients with CHF.5 It is clear that
atrial pathology affects cellular electrophysiology and that the latter
changes contribute to arrhythmogenesis. However, the information about
ionic alterations obtained from studies in human tissues is limited by
various disease states, duration of disease, drug therapy, and numbers
of patients with AF in each study. For example, in the study by Le
Grand et al5 of ionic currents in patients with dilated
atria, 25% of patients also had AF. In the study by Van Wagoner et
al6 of K+ current changes in
patients with AF, all the tissue samples were from patients with
significant dilation of 
1 atria.
Sustained atrial tachycardia causes a substrate that
supports AF and at the cellular level reduces APD and APD rate
adaptation.7 Although CHF also produced a substrate for AF
in the present study, APD was unchanged at slower rates and
increased at faster rates. APD adaptation was reduced, but not as much
as with atrial tachycardia. The differences in APD
remodeling between the CHF and atrial tachycardia models
are associated with differences in ionic current changes. Atrial
tachycardia reduces ICa by
70% without affecting
IK.7 CHF reduced
ICa to a lesser extent (by 30%),
significantly reduced IK by reducing
IKs (to the same extent as
ICa), and increased the inward current
carried by the NCX. NCX expression is not affected by rapid atrial
pacing,18 and we are not aware of previous studies of
atrial NCX current in patients with CHF. In the atrial
tachycardia model, strong reductions in
ICa largely account for decreases in APD
and APD rate adaptation.7 19 In CHF cells, the
ICa reductions are offset by decreases in
IK and increases in NCX, which probably
accounts for the lack of APD alterations at slow rates. The attenuated
rate adaptation caused by ICa reduction may
account for the increased APD at faster rates.
Comparison of Atrial Electrophysiological
Abnormalities With Those in Ventricular Myocytes Caused
by CHF
We are unaware of other studies of the impact of experimental CHF
on atrial cellular electrophysiology. There is, however, an extensive
literature regarding ventricular cellular abnormalities
caused by CHF. Ventricular Ito
is decreased in dogs with pacing-induced CHF8 and in
cardiomyopathic Syrian hamsters.20
Conflicting results have been reported for ventricular
L-type ICa, with either a
reduction9 20 or no change8 21 reported.
Ventricular APD is generally prolonged by
CHF.8 20 Ventricular
IK1 is reduced in both
experimental8 20 and clinical22 CHF.
Ventricular NCX is increased by experimental CHF and
probably plays an important role in APD prolongation and
ventricular tachyarrhythmia promotion at
the ventricular level.13
Potential Significance
The APD decrease caused by atrial tachycardia plays an
important role in leading to multiple-circuit reentrant
AF.7 23 The lack of APD decrease in CHF cells suggests
other mechanisms of AF promotion. Previous work from our laboratory
suggests that structural changes, particularly interstitial
fibrosis, cause important local conduction abnormalities that may play
a central role in the reentrant substrate of CHF-related
AF.23 24 The NCX increases that we noted in the
present study may be quite important in atrial arrhythmia
promotion by CHF. The NCX is known to carry transient inward currents
that cause DADs and triggered activity.14 25 Stambler and
coworkers have observed atrial tachycardias with properties
of triggered arrhythmias in dogs with CHF,25A
to which increased NCX could well be an important contributor.
AF is readily induced in CHF dogs by atrial burst pacing but not by
single extrastimuli.24 Therefore, atrial
tachycardias caused by NCX-related triggered activity may
be the trigger needed to initiate AF in the presence of the CHF-induced
structural substrate. We did not observe triggered activity or DADs
during AP recording in vitro. Additional conditions present
in vivo in the setting of CHF, such as increased
catecholamines, tissue stretch, and metabolic
abnormalities, may therefore be necessary to produce triggered
activity.
Our results could have potential implications for understanding the effects of antiarrhythmic drug therapy on AF. Most antiarrhythmic drugs act by inhibiting cardiac ion channels, so any change in the relative importance of currents flowing during the AP could have a major impact on the action of antiarrhythmic drugs. For example, we have found dofetilide to be unusually effective in terminating AF in dogs with experimental CHF.25B This greater efficacy may be due to CHF-induced downregulation of atrial IKs, leaving repolarization more dependent on IKr.
The development of the atrial tachycardia model of AF was an important advance in studying the arrhythmia.23 26 27 It provided a reliable and reproducible animal model of AF, in which the cellular and ionic mechanisms underlying the arrhythmia substrate could be studied.7 The present study adds a new element to our understanding of the cellular electrophysiological basis of AF by showing that experimentally induced ventricular failure produces a substrate for AF with different AP and ionic changes from those caused by atrial tachycardia. Both of these experimental paradigms are important for our understanding of the cellular basis of AF in humans. When AF begins in patients with CHF, the underlying cellular electrophysiological milieu is established by the ionic current abnormalities caused by CHF. Should AF persist, the resulting atrial tachycardia will cause further atrial cellular remodeling, superimposing tachycardia-induced changes on the underlying CHF substrate. This dynamic nature of the cellular substrate for AF is important to appreciate in order to understand the factors controlling the occurrence and perpetuation of the arrhythmia.
Potential Limitations
IK is very sensitive to isolation
procedures,10 and therefore, changes in isolation
technique could contribute to differences in
IK when several groups are compared. To
minimize possible effects of time-dependent changes in enzymes,
isolation procedure, etc, animals from each group were studied
concurrently in an alternating fashion. Rundown can be a problem in
studies of IK and
ICa. All current protocols were applied in
the same order for control and CHF cells. Cells with significant
rundown (>10% over 20 minutes) were rejected.
We studied a specific animal model of CHF, which has a clinical counterpart in tachycardia-induced ventricular cardiomyopathies28 but which may be different in specific aspects of pathophysiology from other forms of clinical CHF. Furthermore, such issues as the rate of development of CHF, the neuroendocrine response, and the distribution of hemodynamic load may be important determinants of ionic changes. Ionic heterogeneity is significant in the canine atrium,29 and it is therefore essential to compare cells from the same region(s) in CHF dogs versus normal dogs. We studied cells from right atrial pectinate muscles to compare with previous studies of tachycardia-induced ionic remodeling performed with right atrial pectinate myocytes.7 Further work on regional variability in remodeling would be interesting but is outside the scope of this study.
Conclusions
We have found that experimental CHF promotes AF and causes
discrete changes in atrial AP properties and currents. NCX
overexpression may be particularly important by promoting the
occurrence of arrhythmogenic afterdepolarizations. The differences
between CHF-induced atrial cellular
electrophysiological remodeling and that
caused by atrial tachycardia point to the potentially
variable ionic pathophysiology associated with different substrates
for AF. These results are of fundamental importance for our
understanding of basic atrial arrhythmia mechanisms and the
response to antiarrhythmic drugs.
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Acknowledgments |
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This work was supported by the Medical Research Council of Canada and the Quebec Heart Foundation. Danshi Li is a Heart and Stroke Foundation of Canada (HSFC) fellow, and Peter Melnyk is an HSFC student. The authors thank Emma De Blasio and Mirie Levi for technical assistance and France Thériault for secretarial help.
Received October 12, 1999; revision received December 14, 1999; accepted December 22, 1999.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Murgatroyd F, Camm AJ. Atrial arrhythmias. Lancet. 1993;341:1317–1322.[Medline] [Order article via Infotrieve]
2.
Mary-Rabine L, Albert A, Pham TD, et al. The
relationship of human atrial cellular electrophysiology to clinical
function and ultrastructure. Circ Res. 1983;52:188–199.
3. Ouadid H, Albat B, Nargeot J. Calcium currents in diseased human cardiac cells. J Cardiovasc Pharmacol. 1995;25:282–291.[Medline] [Order article via Infotrieve]
4.
Koumi SI, Arentzen CE, Backer CL, et al.
Alterations in muscarinic K+ channel response to
acetylcholine and to G protein–mediated activation in atrial myocytes
isolated from failing human hearts. Circulation. 1994;90:2213–2224.
5. Le Grand B, Hatem S, Deroubaix E, et al. Depressed transient outward and calcium currents in dilated human atria. Cardiovasc Res. 1994;28:548–556.[Medline] [Order article via Infotrieve]
6.
Van Wagoner DR, Pond AL, McCarthy PM, et al. Outward
K+ current densities and Kv1.5 expression are
reduced in chronic human atrial fibrillation. Circ Res. 1997;80:772–781.
7.
Yue L, Feng J, Gaspo R, et al. Ionic remodeling
underlying action potential changes in a canine model of atrial
fibrillation. Circ Res. 1997;81:512–525.
8.
Kääb S, Nuss HB, Chiamvimonvat N, et al.
Ionic mechanism of action potential prolongation in
ventricular myocytes from dogs with pacing-induced heart
failure. Circ Res. 1996;78:262–273.
9. Mukherjee R, Hewett KW, Spinale FG. Myocyte electrophysiological properties following the development of supraventricular tachycardia-induced cardiomyopathy. J Mol Cell Cardiol. 1995;27:1333–1348.[Medline] [Order article via Infotrieve]
10.
Yue L, Feng J, Li GR, et al. Transient outward and
delayed rectifier currents in canine atrium: properties and role of
isolation methods. Am J Physiol. 1996;270:H2157–H2168.
11.
Yue L, Feng J, Li GR, et al. Characterization of an
ultrarapid delayed rectifier potassium channel involved in canine
atrial repolarization. J Physiol (Lond). 1996;496:647–662.
12. Li GR, Nattel S. Demonstration of an inward Na+-Ca2+ exchange current in adult human atrial myocytes. Ann N Y Acad Sci. 1996;779:525–528.[Medline] [Order article via Infotrieve]
13.
O’Rourke B, Kass DA, Tomaselli GF, et al. Mechanisms
of altered excitation-contraction coupling in canine
tachycardia-induced heart failure, I: experimental studies.
Circ Res. 1999;84:562–570.
14.
Blaustein M, Lederer WJ. Sodium/calcium exchange: its
physiological implications. Physiol Rev. 1999;79:763–854.
15.
Boyden PA, Hoffman BF. The effects on atrial
electrophysiology and structure of surgically induced right atrial
enlargement in dogs. Circ Res. 1981;49:1319–1331.
16. Boyden PA, Tilley LP, Pham TD, et al. Effects of left atrial enlargement on atrial transmembrane potentials and structure in dogs with mitral valve fibrosis. Am J Cardiol. 1982;49:1896–1908.[Medline] [Order article via Infotrieve]
17.
Boyden PA, Tilley LP, Albala A, et al. Mechanisms for
atrial arrhythmias associated with
cardiomyopathy: a study of feline hearts with
primary myocardial disease. Circulation. 1984;69:1036–1047.
18.
Yue L, Melnyk P, Gaspo R, et al. Molecular mechanisms
underlying ionic remodeling in a dog model of atrial fibrillation.
Circ Res. 1999;84:776–784.
19.
Courtemanche M, Ramirez RJ, Nattel S. Ionic targets for
drug therapy and atrial fibrillation-induced electrical remodeling:
insights from a mathematical model. Cardiovasc Res. 1999;42:477–489.
20. Thuringer D, Deroubaix E, Coulombe A, et al. Ionic basis of the action potential prolongation in ventricular myocytes from Syrian hamsters with dilated cardiomyopathy. Cardiovasc Res. 1996;31:747–757.[Medline] [Order article via Infotrieve]
21.
Sen L, Smith TW. T-type Ca2+
channels are abnormal in genetically determined
cardiomyopathic hamster hearts. Circ Res. 1994;75:149–155.
22.
Beuckelmann DJ, Nabauer M, Erdmann E. Alterations of
K+ currents in isolated human
ventricular myocytes from patients with terminal heart
failure. Circ Res. 1993;73:379–385.
23. Nattel S, Li D, Yue L. Basic mechanisms of atrial fibrillation: very new insights into very old ideas. Annu Rev Physiol. 2000;62:51–77.[Medline] [Order article via Infotrieve]
24.
Li D, Fareh S, Leung TK, et al. Promotion of atrial
fibrillation by heart failure in dogs: atrial remodeling of a different
sort. Circulation. 1999;100:87–95.
25.
Benardeau A, Hatem SN, Rucker-Martin C, et al.
Contribution of Na+/Ca2+
exchange to action potential of human atrial myocytes. Am J
Physiol. 1996;271:H1151–H1161.
25. Fenelon G, Manders T, Stambler BS. Atrial tachycardia in dogs with ventricular pacing-induced congestive heart failure originates from multiple foci in the crista terminalis and pulmonary veins: experimental evidence supporting the "atrial ring of fire" hypothesis. Circulation. 1997;96:I-237. Abstract.
25. Li D, Benardeau A, Nattel S. Contrasting efficacy of dofetilide in differing experimental models of atrial fibrillation. Circulation. In press.
26.
Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial
fibrillation begets atrial fibrillation: a study in awake chronically
instrumented goats. Circulation. 1995;92:1954–1968.
27.
Morillo CA, Klein GJ, Jones DL, et al. Chronic rapid
atrial pacing: structural, functional, and
electrophysiological characteristics of a
new model of sustained atrial fibrillation. Circulation. 1995;91:1588–1595.
28. Packer DL, Bardy GH, Worley SJ, et al. Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction. Am J Cardiol. 1986;57:563–570.[Medline] [Order article via Infotrieve]
29.
Feng J, Yue L, Wang Z, et al. Ionic mechanisms of
regional action potential heterogeneity in the canine
right atrium. Circ Res. 1998;83:541–551.
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 P. Khairy and S. Nattel New insights into the mechanisms and management of atrial fibrillation Can. Med. Assoc. J., October 29, 2002; 167(9): 1012 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
R. F Bosch and S. Nattel Cellular electrophysiology of atrial fibrillation Cardiovasc Res, May 1, 2002; 54(2): 259 - 269. [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel Therapeutic implications of atrial fibrillation mechanisms: can mechanistic insights be used to improve AF management? Cardiovasc Res, May 1, 2002; 54(2): 347 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
K. Shinagawa, D. Li, T. K. Leung, and S. Nattel Consequences of Atrial Tachycardia-Induced Remodeling Depend on the Preexisting Atrial Substrate Circulation, January 15, 2002; 105(2): 251 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shivkumar and J. N Weiss Atrial fibrillation: from cells to computers Cardiovasc Res, November 1, 2001; 52(2): 171 - 173. [Full Text] [PDF]
|
|
|
|
|
|
W. Han, D. Chartier, D. Li, and S. Nattel Ionic Remodeling of Cardiac Purkinje Cells by Congestive Heart Failure Circulation, October 23, 2001; 104(17): 2095 - 2100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.J.G.M. Crijns, T. van Noord, and I.C. van Gelder Recurrence of atrial fibrillation and the need for new definitions Eur. Heart J., October 1, 2001; 22(19): 1769 - 1771. [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 C.-C. Shieh, M. Coghlan, J. P. Sullivan, and M. Gopalakrishnan Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities Pharmacol. Rev., December 1, 2000; 52(4): 557 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nattel Acquired delayed rectifier channelopathies: how heart disease and antiarrhythmic drugs mimic potentially-lethal congenital cardiac disorders Cardiovasc Res, November 1, 2000; 48(2): 188 - 190. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
D. Li, L. Zhang, J. Kneller, and S. Nattel Potential Ionic Mechanism for Repolarization Differences Between Canine Right and Left Atrium Circ. Res., June 8, 2001; 88(11): 1168 - 1175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Boixel, W. Gonzalez, L. Louedec, and S. N. Hatem Mechanisms of L-Type Ca2+ Current Downregulation in Rat Atrial Myocytes During Heart Failure Circ. Res., September 28, 2001; 89(7): 607 - 613. [Abstract] [Full Text] [PDF]
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