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(Circulation. 1997;96:1551-1556.)
© 1997 American Heart Association, Inc.
Articles |
Hysteresis of the RT Interval With Exercise
A New Marker for the Long-QT Syndrome?
From the Division of Cardiology, Department of Medicine, University of Western Ontario, Canada.
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Abstract |
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Background The diagnosis of the long-QT syndrome (LQTS) may be difficult to establish in patients with normal or borderline prolongation of the QT interval. Noninvasive markers are needed to identify patients with LQTS.
Methods and Results Fourteen patients with known LQTS, 9
unaffected family members, and 40 control subjects underwent modified
Bruce protocol exercise testing. The RT interval (peak of R wave to
peak of T wave) and rate-corrected RT interval (RTc) were measured
during exercise and recovery. The RT interval at 1 minute into recovery
was subtracted from the RT interval at a similar heart rate during
exercise (
RT). The RTc shortened by 61 milliseconds (ms) in the LQTS
patients compared with 23 to 26 ms in the other two groups
(P=.003 by ANOVA). The RT interval shortened in a linear
fashion in all patients but demonstrated persistent shortening during
recovery in the LQTS patients. This was manifested as a hysteresis loop
in the curve relating the RT interval to cycle length. The hysteresis
loop was present in 13 of 14 LQTS patients and only 4 of 40 control
subjects. RT >25 ms had a sensitivity of 73%, a specificity of
92%, a positive predictive value of 79%, and a negative predictive
value of 90% for LQTS.
Conclusions Hysteresis of the RT interval with exercise may be useful for the diagnosis of LQTS.
Key Words: exercise • electrocardiography • intervals • death, sudden
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The long-QT syndrome (LQTS) is characterized by exercise- or stress-induced syncope or sudden death associated with a prolonged corrected QT interval (QTc) and polymorphic ventricular tachycardia. Recent studies1 2 3 4 in several large kindreds using DNA linkage analysis have demonstrated at least three different culprit genes associated with LQTS. These genetic markers are useful predictors of genotypic carrier status among family members of patients with LQTS, but phenotypic expression of the underlying gene is assessed by clinical presentation and abnormalities of the QT interval. The latter may be intermittent or equivocal. We describe the marked persistence of exercise-induced shortening of the RT interval (peak of R wave to peak of T wave) during the immediate postexercise recovery period in patients with LQTS that is not observed in normal subjects and may provide the basis for a useful noninvasive marker for LQTS.
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Methods |
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Patients
Patients were divided into three groups. Group 1 included 14 patients who scored
4 points according to the 1993 LQTS
diagnostic criteria indicating definite LQTS.5
Patients were drawn from five kindreds with known LQTS. All patients
had a positive family history of exercise-induced syncope or premature
sudden cardiac death. Group 2 included 9 family members of group 1
patients who were free of symptoms and had a normal QT interval. Group
3 included 40 normal control subjects who were healthy volunteers free
of structural heart disease, syncope, or family history of
exercise-induced syncope or sudden cardiac death.
Investigations
Exercise Testing
All patients underwent a symptom-limited treadmill test using a
modified Bruce protocol. Twelve-lead ECGs were recorded on all
patients at rest in the supine and upright positions; at 3-minute
intervals during exercise; at peak exercise; and at 1, 2, 4, and 6
minutes after peak exercise during recovery. Blood pressure, heart
rate, and symptoms were monitored during exercise and recovery. All
patients had discontinued ß-blockers or antiarrhythmic agents at
least five drug half-lives before testing. No patient had evidence of
hypertrophic cardiomyopathy or arrhythmogenic right
ventricular dysplasia on physical examination or with
myocardial imaging.
ECG Measurements
ECGs were acquired at a paper speed of 25 mm/s. The QT
interval was measured from the onset of the QRS complex to the point of
return of the T wave to baseline. In the presence of U waves, the point
of intersection of the downsloping T wave with the isoelectric baseline
was used as the end of the T wave. The longest QT interval measured in
the precordial leads was used. Because of the difficulty in
measuring the QT interval at rapid heart rates and the subjective
nature of the measurement of the termination of the T wave, the RT
interval was measured at rest and during exercise.6 It was
defined as the interval from the peak of the R wave to the peak of the
T wave in the precordial lead with the maximally peaked R and T
waves during peak exercise (usually V2 through
V4). The same lead was used at rest and throughout exercise
for calculation of the RT interval. This technique, which used the
peaks of the R and T waves, minimized the potential for observer bias
in the manual acquisition of data. All measurements were made manually
by a single observer. RT intervals in all LQTS patients were measured
with manual calipers as well as with a crosshairs mouse with a
digitizing tablet calibrated at the time of reading. The correlation
coefficient (r) of the two techniques in individual patients
ranged from .994 to .999. The mean difference in RT measurements
between two observers was 4.1 ms (interobserver variability), and the
mean difference between separate blinded readings by a single observer
(A.K.) was 3.2 ms (intraobserver variability).
The QT and RT intervals were corrected for rate using Bazett's
formula (QT or RT/
RR interval measured in seconds).7
The RT interval at 1, 2, and 4 minutes during recovery was compared
with the RT interval at a similar heart rate (within 10 bpm) during
exercise. The RT was defined as the exercise RT interval minus the
recovery RT interval at a similar heart rate. To correct for small
differences in heart rate in the calculation of RT, the corrected
RT (RTc) was also calculated using Bazett's formula as well as
the correction of Sagie et al8 based on a linear
regression model [QTLC=QT+0.154(1-RR)].
Statistical Analysis
Continuous variables were compared by use of ANOVA and a
two-tailed t test. Multiple comparisons were performed by
use of a t test with a Bonferroni correction. Categorical
variables were compared by 
2 test. A
correlation coefficient (r) was calculated for the QT and RT
intervals. Sensitivity was defined as the number of true-positives
divided by the sum of true-positives and false-negatives. Specificity
was defined as the number of true-negatives divided by the sum of
true-negatives and false-positives. A receiver operator curve (ROC) for
the RT was generated plotting sensitivity (y axis) versus
1-specificity (x axis). Data are presented as
mean±SD. A value of P<.05 was considered significant.
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Results |
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Clinical characteristics of the three groups were similar (Table 1
). The resting RT, QT, RTc, and QTc
intervals were significantly longer in group 1 than in the other two
groups (P<.001 by t test, P<.001 by
ANOVA). There was no difference in the resting or peak heart rate,
change in heart rate, duration of exercise, or metabolic
equivalents performed. The QTc and RTc intervals were longer in women
in all four groups. The QT and RT intervals at rest for all patients
were highly correlated (r=.75, P<.001). The
exercise RT interval was strongly correlated with the QT interval in
the three group 1 and three group 3 patients tested (r=.90
to .97, P<.001).
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Change in RTc With Exercise
Group 1 patients demonstrated a prolonged RTc interval at rest
that shortened significantly with exercise and remained shortened
during the early recovery period (Fig 1).
In contrast, the other two groups had a minimal change in RTc interval
with exercise, with no significant RTc shortening in the recovery
phase. The RTc interval shortened by 61 ms in group 1 compared with 26
and 23 ms in groups 2 and 3, respectively (Table 2) (P=.003 by ANOVA).
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RT Interval and Cycle Length
The relationship between RT interval and cycle length during
exercise and recovery was examined in all three groups. Patients in
group 1 showed a linear relation between the RT interval and cycle
length with exercise (Fig 2). During the
recovery phase, the RT interval remained shortened despite a
decelerating heart rate, forming a hysteresis "loop" in the curve
relating the RT interval to the cycle length (Fig 3). Patients in groups 2 and 3
demonstrated similar linear shortening of the RT interval with
exercise, but the marked persistent shortening seen in early recovery
was not evident.
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RT Interval
To determine the magnitude of hysteresis, the RT interval at 1, 2,
and 4 minutes into recovery was compared with the RT interval at a
similar heart rate during exercise (RT and RTc). Patients in
group 1 demonstrated a significantly higher RT and RTc than group
2 and 3 patients at all three time intervals (P
.001 at 1
and 2 minutes, P<.05 at 4 minutes by ANOVA). Use of the
RTc interval to correct for small differences in the heart rate did
not improve discrimination between the three groups with either the
Bazett's or linear regression technique. When the RT was expressed
as a percentage of the baseline RT, the results remained significant at
1 and 2 minutes (P<.001 by ANOVA) but not at 4 minutes
(P=.09 by ANOVA).
When the mean differences in RT at the three time intervals (1, 2,
and 4 minutes) were compared, the RT at 1 minute showed the greatest
discrimination between groups. Fig 4
presents individual data points for the RT at 1 minute for all
three groups. An arbitrary cutoff value of 25 ms for the RT at 1
minute was chosen to differentiate group 1 patients from group 3
control subjects, ie, the 1-minute recovery RT interval had to be at
least 25 ms shorter than the RT interval at a similar heart rate during
exercise. When this cutoff was used, the sensitivity was 73%, the
specificity was 92%, the positive predictive value was 79%, and the
negative predictive value was 90%. Fig 5
is an ROC that examines the use of the RT at 1 minute to
discriminate normal subjects from group 1 patients. The area under the
ROC curve was 0.90 (95% CI, 0.77 to 0.98).
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To further characterize the changes in RT interval, the change in RTc
and RT at 1 minute was examined by family (Table 3). The first family with the largest
shortening of the RTc had late-peaking low-amplitude T waves
consistent with LQT3 associated with a mutation of the sodium
channel gene on chromosome 3 (SCN5A). The single affected
member of family 4 had similar late-peaking T waves. This patient had
poor exercise tolerance, performing only 6 minutes of the modified
Bruce protocol, increasing her heart rate from 90 to 146 bpm. The third
family had a QTc near the upper limit of normal with exercise-induced
syncope, sudden death in two family members, and a documented
ventricular fibrillation arrest in one patient. The fifth
family with the least RTc shortening had broad-based and notched T
waves in keeping with a defect on chromosome 11. The remaining family
had inverted T waves in the precordial leads that were not
sufficiently typical to characterize their likely genetic defect.
Within Group 1 patients with LQTS, there was a correlation between the
magnitude of change in RTc with exercise and the RT at 1 minute
(r=.55, P=.04). There was no correlation in the
other two groups (P>.3).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The RT interval in patients with LQTS in this study shortened with exercise to a greater extent than in normal control subjects. Eggeling et al9 found no change in QTc with exercise or with autonomic maneuvers in 14 patients with LQTS. Vincent et al10 examined change in QT and QTc intervals with exercise in 27 LQTS patients and found an increase in the QTc with exercise. Similarly, Shimizu et al11 demonstrated QTc prolongation in 11 LQTS patients during exercise. The mean age in these series was 21, 24, and 21 years, respectively, considerably younger than our mean of 30 years. Recent genetic studies1 2 3 4 have identified three genetic loci responsible for LQTS on chromosomes 3, 7, and 11 with evidence of further genetic heterogeneity, implying other, as-yet-unidentified genetic loci. These defects have been linked with abnormalities of specific intracardiac ion channel genes, SCN5A on chromosome 3 (coding for a sodium channel)3 and HERG on chromosome 7 (coding for a specific potassium channel).1 Because there are electrocardiographic differences between the LQTS types,12 13 it may well be that the QTc response to exercise differs between the different genotypic defects in LQTS on the basis of the underlying ion channel affected. A recent report14 suggested that the defect in chromosome 3 linked to a mutation of the SCN5A sodium channel gene is associated with proportionally greater shortening of the QTc than that associated with defects in chromosomes 7 and 11. The present study involved LQTS patients from five different kindreds. Because genetic typing has not been performed in our patients, it may be that the observed shortening of the RTc in our series reflects a different patient population than those studied by some authors, ie, a larger representation of the SCN5A defect. This is supported by the largest change in the RTc with exercise in the family with late-peaking low-amplitude T waves, in keeping with the chromosome 3 defect.
Patients with LQTS in our series demonstrated a hysteresis loop in the
curve relating the RT interval to cycle length with persistent
shortening of the RT interval during the recovery phase in the context
of normal rate deceleration. Hysteresis of the QT interval with
exercise has been described in normal subjects by Sarma et
al.15 Persistent shortening of the QT interval during
recovery was noted in 14 patients undergoing stress testing for various
reasons. Four of the patients were receiving ß-blockers and 2 were
receiving antiarrhythmic drugs. The authors calculated the area under
the exercise curve in the first 150 ms of RR-interval prolongation
after peak exercise to express hysteresis. Arnold et al16
also noted a lag between change in heart rate and subsequent adaptation
of the QT interval in 3 healthy volunteers. Sundqvist and
Sylven17 found a 26-ms difference between the exercise and
30-second–recovery QT intervals in 11 healthy volunteers and noted
that most of this hysteresis phenomenon was explained by differences in
the Q-wave–to–peak T-wave measurement. Rickards and
Norman18 did not see evidence of hysteresis in 25 patients
undergoing exercise testing for investigation of chest pain. We found a
small degree of hysteresis in our normal population, with a 10- to
16-ms difference between the exercise and recovery curves at 1 to 4
minutes of recovery (RT). Hysteresis was much more marked in the
LQTS population, with a 28- to 48-ms difference in the two curves
between 1 and 4 minutes.
The mechanism of the RT hysteresis phenomenon is unclear. Several authors19 20 21 have examined the effect of sudden change in stimulation rate on action-potential duration in isolated ventricular and His-Purkinje preparations, similar to the sudden change in rate that accompanies the early postexercise recovery period. Persistent shortening of action-potential duration after sudden prolongation of stimulation-cycle length has been observed in some but not all species studied. In addition, the time course to return to steady state varies between models, from as little as 40 seconds in the dog21 to 10 minutes in the frog.20 Because the early recovery period is characterized by a sudden slowing of heart rate, it is possible that the rate change alone, independent of the effect of circulating catecholamines, contributes to the hysteresis phenomenon.
Arrowood et al22 examined the change in QT interval with exercise in cardiac transplant patients and found a similar QT-shortening response in transplant patients compared with control subjects. The authors concluded that QT shortening is largely mediated by circulating catecholamines. Of interest, studies in cell preparations have demonstrated that norepinephrine and epinephrine slightly lengthen ventricular action-potential duration.23 24 Rickards and Norman18 demonstrated that the degree of QT shortening with exercise is not obtained with pacing at similar rates and that exercise with fixed-rate pacing was associated with QT shortening, further supporting the role of circulating catecholamines in QT shortening. Plasma norepinephrine levels rise with exercise and continue to rise early in recovery, with a half-life of 2.8 minutes.25 26 It is possible that the persistent catecholamine effect early in the recovery period explains the modest degree of hysteresis found in normal subjects in the present study, resulting in ongoing QT shortening during parasympathetically mediated heart rate deceleration. The marked hysteresis in LQTS patients may reflect an exaggerated response of the underlying abnormal sodium or potassium channel to persistent catecholamines in the early recovery period or an exaggerated phase lag in shortening of recovery of the culprit channel.
Hysteresis was also seen in two patients with a normal resting QT
interval and exercise-induced syncope but in only a small proportion of
normal subjects. In a large international registry, 6% of patients
subsequently diagnosed with LQTS had a QTc 440 ms, 15% did not have
a family member with a prolonged QTc, and 40% had a negative family
history for syncope or sudden death.27 28 Follow-up of
these individuals may yet reveal progressive QT abnormalities or
document an arrhythmia in conjunction with symptoms.
Study Limitations
The RT interval was used in this study as a surrogate of the QT
interval, the accepted measurement to quantify repolarization. However,
the abnormal configuration of repolarization in LQTS patients often
makes the precise end of the T wave difficult to determine in LQTS
patients. This problem is further hampered by fusion of the T and p
waves at higher rates with exercise. Several recent studies have shown
that the RT interval or QT peak is also prolonged in patients with LQTS
and correlates with the QT interval in normal subjects and LQTS
patients.6 12 29 Use of the RT interval facilitates the
development of automated technology to measure and quantify the
duration of repolarization and the extent of hysteresis. The use of the
peaks of the R and T waves minimized the potential for observer bias in
the manual acquisition of data. Manually acquired data were used in
several other series that examined the change in QT interval with
exercise.9 10 11
Second, these observations were made on a small sample and require
validation in a larger cohort of LQTS patients. However, the infrequent
occurrence of marked hysteresis among a modest sample of normal control
subjects suggests that a normal range can be identified for comparative
use with other LQTS or suspected LQTS patients. In addition,
correlation with genetic typing may reveal different QT "loops"
in the various LQTS types. This is supported by the correlation between
the degree of RTc shortening with exercise and the extent of hysteresis
as measured by the RT at 1 minute.
Third, the manual measurement of data points at normal paper speed raises concern about measurement error. Subsequent validation of these observations should involve an accurate and automated method of measurement.
Finally, insufficient data points for individual patients precluded the
accurate statistical comparison of the actual slope of the exercise and
recovery RT-RR curves. However, simple comparison of the RT interval 1
minute into recovery promises to be a readily accessible means of
quantifying hysteresis. The sensitivity and predictive value of the
RT are imperfect but are in keeping with other accepted screening
tests. The combination of this information with other phenotypic
markers may enhance diagnostic yield.
In spite of these limitations, the RT hysteresis "loop" may prove
to be a useful noninvasive marker for the phenotypic expression of
LQTS. The hysteresis loop and measurement of the RT are easily
obtained from established exercise test technology. This test may prove
to be useful in patients suspected of having LQTS who do not have
diagnostic ECGs.
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Footnotes |
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Reprint requests to Dr Andrew Krahn, University Campus, London Health Sciences Center, 339 Windermere Rd, London, Ontario, Canada N6A 5A5.
Received January 2, 1997; revision received April 11, 1997; accepted April 18, 1997.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Curran ME, Splawski I, Timothy KW, Vincent M,
Green ED, Keating MT. A molecular basis for cardiac
arrhythmia: HERG mutations cause long QT syndrome.
Cell. 1995;80:795-803.[Medline]
[Order article via Infotrieve]
-
Towbin JA, Li H, Taggart T, Lehmann MH, Schwartz PJ,
Satler CA, Ayyagari R, Robinson JL, Moss A, Hejtmancik JF.
Evidence of genetic heterogeneity in Romano-Ward long
QT syndrome: analysis of 23 families.
Circulation. 1994;90:2635-2644.
[Abstract/Free Full Text]
-
Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson
JL, Moss AJ, Keating MT. SCN5A mutations cause an inherited
cardiac arrhythmia, long QT syndrome. Cell. 1995;80:805-811.[Medline]
[Order article via Infotrieve]
-
Jiang C, Atkinson D, Towbin JA, Splawski I, Lehmann
MH, Li H, Timothy K, Taggart RT, Schwartz PJ, Vincent GM, Moss A,
Keating MT. Two long QT syndrome loci map to chromosomes 3 and 7
with evidence for further heterogeneity.
Nat Genet. 1994;8:141-147.[Medline]
[Order article via Infotrieve]
-
Schwartz PJ, Moss AJ, Vincent GM, Crampton RS.
Diagnostic criteria for the long QT syndrome.
Circulation. 1993;88:782-784.
[Free Full Text]
-
Merri M, Benhorin J, Alberti M, Locati E, Moss
AJ. Electrocardiographic quantitation of ventricular
repolarization. Circulation. 1989;80:1301-1308.
[Abstract/Free Full Text]
-
Bazett HC. An analysis of time
relations of electrocardiograms.
Heart. 1920;7:353-370.
-
Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy
D. An improved method for adjusting the QT interval for heart
rate (the Framingham Heart Study). Am J
Cardiol. 1992;70:797-801.[Medline]
[Order article via Infotrieve]
-
Eggeling T, Hoeher M, Osterhues HH, Weismueller P,
Hombach V. Significance of noninvasive diagnostic
techniques in patients with long QT syndrome. Am J
Cardiol. 1992;70:1421-1425.[Medline]
[Order article via Infotrieve]
-
Vincent GM, Jaiswal D, Timothy KW. Effects of
exercise on heart rate, QT, QTc and QT/QS2 in the Romano-Ward inherited
long QT syndrome. Am J Cardiol. 1991;68:498-503.[Medline]
[Order article via Infotrieve]
-
Shimizu W, Ohe T, Kurita T, Shimomura K.
Differential response of QTU interval to exercise, isoproterenol, and
atrial pacing in patients with congenital long QT syndrome.
Pacing Clin Electrophysiol. 1991;14:1966-1970.[Medline]
[Order article via Infotrieve]
-
Moss AJ, Zareba W, Benhorin J, Locati EH, Hall WJ,
Robinson JL, Schwartz PJ, Towbin JA, Vincent GM, Lehmann MH, Keating
MT, MacCluer JW, Timothy KW. ECG T-wave patterns in genetically
distinct forms of the hereditary long QT syndrome.
Circulation. 1995;92:2929-2934.
[Abstract/Free Full Text]
-
Lehmann MH, Suzuki F, Fromm BS, Frankovich D, Elko P,
Steinman RT, Fresard J, Baga JJ, Taggart RT. T wave `humps' as
a potential electrocardiographic marker of the long QT
syndrome. J Am Coll Cardiol. 1994;24:746-754.[Abstract]
-
Schwartz PJ, Priori SG, Locati EH, Napolitano C, Cantu
F, Towbin JA, Keating MT, Hammoude H, Brown AM, Chen LSK, Colatsky
TJ. Long QT syndrome patients with mutations of the
SCN5A gene and HERG genes have differential
responses to Na+ channel blockade and to increases in heart
rate: implications for gene-specific therapy. Circulation. 1995;92:3381-3386.
[Abstract/Free Full Text]
-
Sarma JSM, Venkataraman K, Samant DR, Gadgil U.
Hysteresis in the human RR-QT relationship during exercise and
recovery. Pacing Clin Electrophysiol. 1987;10:485-491.[Medline]
[Order article via Infotrieve]
-
Arnold L, Page J, Attwell D, Cannell M, Eisner
DA. The dependence on heart rate of the human
ventricular action potential duration.
Cardiovasc Res. 1982;16:547-551.[Medline]
[Order article via Infotrieve]
-
Sundqvist K, Sylven C. Cardiac repolarization
properties during standardized exercise test as studied by QT, QT peak
and terminal T-wave intervals. Clin Physiol. 1989;9:419-425.[Medline]
[Order article via Infotrieve]
-
Rickards AF, Norman J. Relation between QT
interval and heart rate: new design of
physiologically adaptive cardiac
pacemaker. Br Heart J. 1982;45:56-61.
[Abstract/Free Full Text]
-
Nolasco JB, Dahlen RW. A graphic method for the
study of alternation in cardiac action potentials. J
Appl Physiol. 1968;25:191-196.
[Free Full Text]
-
Carmeliet E. Repolarisation and frequency in
cardiac cells. J Physiol (Lond). 1977;73:903-923.
-
Boyett MR, Jewell BR. Analysis of the
effects of changes in rate and rhythm upon electrical activity in the
heart. Prog Mol Biol. 1980;36:1-52.
-
Arrowood JA, Kline J, Simpson PM, Quigg RJ, Pippin JJ,
Nixon JV, Mohanty PK. Modulation of the QT interval: effects of
graded exercise and reflex cardiovascular
stimulation. J Appl Physiol. 1993;75:2217-2223.
[Abstract/Free Full Text]
-
Morad M, Rolett EL. Relaxing effects of
catecholamines on mammalian heart. J
Physiol (Lond). 1972;224:537-558.
[Abstract/Free Full Text]
-
Reuter H. Localization of beta adrenergic
receptors, and effects of noradrenaline and cyclic
nucleotides on action potentials, ionic currents and
tension in mammalian cardiac muscle. J Physiol
(Lond). 1974;242:429-451.
[Abstract/Free Full Text]
-
Hagberg JM, Hickson RC, McLane JA, Ehsani AA, Winder
WW. Disappearance of norepinephrine from the
circulation following strenuous exercise. J Appl
Physiol. 1979;47:1311-1314.
[Abstract/Free Full Text]
-
Dimsdale JE, Hartley LH, Guiney T, Ruskin JN,
Greenblatt D. Postexercise peril: plasma
catecholamines and exercise. JAMA. 1984;251:630-632.[Abstract]
-
Moss AJ, Schwartz PJ, Crampton RS, Tzivoni D, Locati
EH, MacCluer J, Hall WJ, Weitkamp L, Vincent GM, Garson A, Robinson JL,
Benhorin J, Choi S. The long QT syndrome: prospective
longitudinal study of 328 families. Circulation. 1991;84:1136-1144.
[Abstract/Free Full Text]
-
Garson A, Macdonald D II, Fournier A, Gillette PC,
Hamilton R, Kugler JD, Van Hare GF, Vetter V, Vick GW. The long
QT syndrome in children: an international study of 287
patients. Circulation. 1993;87:1866-1872.
[Abstract/Free Full Text]
-
Benhorin J, Merri M, Alberti M, Locati E, Moss AJ, Hall
WJ, Cui L. Long QT syndrome: new electrocardiographic
characteristics. Circulation. 1990;82:521-527.
[Abstract/Free Full Text]
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