Vol. 282, Issue 6, H2091-H2098, June 2002
Parasympathetic effects on cardiac electrophysiology during
exercise and recovery
Prince J.
Kannankeril and
Jeffrey J.
Goldberger
Division of Cardiology, Department of Medicine, Northwestern
University, Chicago, Illinois 60611
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ABSTRACT |
Depressed parasympathetic tone is
associated with an increased risk of sudden cardiac death. Exercise and
the postexercise recovery period, which are associated with
parasympathetic withdrawal, are high risk periods for sudden death.
However, parasympathetic effects on cardiac electrophysiology during
exercise and recovery have not been described. Electrophysiology
studies were performed using noninvasive programmed stimulation (NIPS)
in nine subjects (age 59 ± 18 yr) with implanted dual-chamber
devices and normal left ventricular function during multiple bicycle
exercise sessions. NIPS was performed at rest, during exercise, and in
the early recovery period both before and after parasympathetic
blockade with atropine. Parasympathetic effect was defined as the value of the parameter of interest in the absence of atropine minus the value
of the parameter in the presence of atropine. During exercise, sinus
cycle length, atrioventricular (AV) block cycle length, AV interval,
and ventricular effective refractory period shortened; in recovery, the
values were intermediate between the rest and exercise values
(P < 0.0001 by ANOVA). Parasympathetic effects on
sinus cycle length, AV block cycle length, AV interval, and
ventricular effective refractory period were 247 ± 140, 58 ± 20, 76 ± 20, and 8.6 ± 7.5 ms at rest, 106 ± 20, 37 ± 14, 24 ± 13, and 2.6 ± 7.8 ms during exercise,
and 209 ± 114, 50 ± 23, 35 ± 21, and 9.5 ± 11.8 ms during recovery, respectively. There was poor correlation among the
parasympathetic effects noted at the sinus node, AV node, and
ventricle. Further work evaluating parasympathetic effects on cardiac
electrophysiology during exercise and recovery in patients with heart
disease is required to elucidate its role in modulating the risk of
sudden cardiac death noted at these times.
exercise
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INTRODUCTION |
THE RISK OF SUDDEN
DEATH is increased nearly 17-fold during and immediately after
exercise (2, 23). While there are several potential
mechanisms for this marked increased risk of sudden cardiac death, it
is possibly related in part to the acute changes in autonomic tone that
accompany exercise. Exercise is associated with increased sympathetic
tone and parasympathetic withdrawal in normal subjects (11, 12,
36). Numerous clinical and experimental studies have provided
evidence linking diminished parasympathetic nervous system activity at
rest with increased mortality and sudden cardiac death (6, 16,
18, 28, 31). Experimental data suggest that dogs with myocardial
infarctions prone to ventricular fibrillation during exercise and
induced ischemia have greater reductions in parasympathetic
tone, as measured by heart rate variability, during exercise compared
with nonsusceptible animals (7). Recent human data have
shown that a small heart rate decrease in the early recovery phase
after exercise is associated with an increased mortality (9, 10,
27). These data suggest that depressed parasympathetic tone
during exercise or depressed recovery of parasympathetic tone after
exercise may be important factors resulting in an increased risk of
sudden cardiac death. Conversely, enhanced parasympathetic tone
may be protective against sudden death (39).
One potential mechanism for the protective effect of parasympathetic
tone is related to its direct effects on cardiac electrophysiology (35). Parasympathetic effects on cardiac electrophysiology
have been described in animal (30) and human
(32) subjects at rest. However, parasympathetic effects on
cardiac electrophysiology during exercise and recovery have not been
described. This study was designed to evaluate parasympathetic effects
on cardiac electrophysiology during rest, exercise, and recovery. We
hypothesized that there are demonstrable parasympathetic effects on
cardiac electrophysiology during exercise and recovery.
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METHODS |
Study design.
In this study, cardiac electrophysiologic parameters were measured
using noninvasive programmed stimulation (NIPS) in subjects with
implanted dual-chamber devices (pacemakers or defibrillators). With the
use of the device, electrophysiological studies could be performed at
rest, during exercise, and during recovery. Directed electrophysiological studies were performed to assess parasympathetic effects at the sinus node, atrioventricular (AV) node, and ventricle. Because most people do not exercise to peak exertion levels and a
several-minute period of "stable" exercise was required to obtain all the electrophysiological measurements, a moderate level
of exertion was used. To evaluate parasympathetic effects, subjects were studied on multiple occasions, so that each state (rest, exercise,
and recovery) was evaluated at least twice: once in the setting of
intact autonomic tone and once after pharmacologic parasympathetic
blockade with atropine. Parasympathetic effect at any state for a given
electrophysiological parameter was defined as the value of the
parameter in the absence of atropine (no parasympathetic blockade)
minus the value of the parameter in the presence of atropine (with
parasympathetic blockade). For example, if sinus cycle length during
exercise was 600 ms and during exercise with atropine was 500 ms, the
parasympathetic effect on sinus cycle length during exercise was 100 ms. In a recent committee report, it was stated that the gold standard
for estimating cardiac vagal tone in humans is derived from
pharmacological blockade (5).
Subjects.
The study group consisted of nine subjects (3 men and 6 women; mean age
59 ± 18 yr) with normal left ventricular function and a
dual-chamber pacemaker (n = 8) or defibrillator
(n = 1) capable of NIPS (Medtronic: 7860 DR, 7960i, KDR
701, GEM DR 7271; Pacesetter: 2360, 5330). A tenth subject was excluded
due to excessive ventricular ectopy during exercise. Because most
patients with devices have some inherent conduction system disease,
attempts were made to recruit subjects with chronotropic competence and intact AV conduction. All nine subjects had some degree of chronotropic competence, defined by an increase in the sinus rate of >15 beats/min during moderate exercise at the first study. Eight of nine subjects had
intact AV node conduction, defined by no more than first-degree heart
block as an underlying rhythm during rest, exercise, and recovery; the
ninth subject had 2:1 AV block during exercise and was not included in
the analysis of AV node function. Table 1 describes the subjects' clinical characteristics and medications. Subjects were on a stable medical regimen throughout the study period.
No subjects had evidence of unstable angina, congestive heart failure,
or myocardial infarction within the preceding 3 mo. Subjects
participated in regular aerobic exercise an average of 150 ± 95 min/wk. Written informed consent was obtained before the study. The
study was approved by the Northwestern University Institutional Review
Board.
Exercise tests.
Subjects were studied in four separate sessions, separated by at least
24 h each for the first three sessions. The third and fourth
sessions were separated by at least 48 h. Subjects were attached
to a pacemaker programmer and electrocardiogram (ECG) machine
(Marquette MAC VU; Milwaukee, WI). All measurements were taken with
subjects seated on a mechanically braked bicycle ergometer (Monark
818E; Vansbro, Sweden). At the first session, a baseline heart rate and
blood pressure were recorded. NIPS (see below) was performed through
the device before exercise. Subjects then performed exercise, keeping
pedal speed between 50 and 60 rpm, with a starting workload of
25-50 W, and adjusting resistance every 2 min until the heart rate
reached 100-110 beats/min. If the target heart rate was not
achieved, a target workload was chosen that would allow the subject to
maintain exercise comfortably at that level for ~10 min. One minute
after reaching the target heart rate or stage, NIPS was repeated during
exercise. Peak heart rate and blood pressure were recorded at the end
of exercise. One minute after exercise ended, NIPS was performed during
recovery, and heart rate and blood pressure were recorded. At the first session, the appropriate bicycle resistance (target workload) was
determined, and the feasibility of NIPS was evaluated.
The second session was identical to the first except that resistance
was set to the target workload (which produced a heart rate of
100-110 beats/min) at the beginning of exercise and was maintained
throughout the duration of exercise. NIPS was performed at rest, during
exercise, and during recovery. The third session was similar to the
second. However, during exercise, just before NIPS, subjects underwent
complete parasympathetic blockade with intravenous atropine (0.04 mg/kg) in divided doses (0.01 mg/kg every 30 s) (15).
NIPS was then performed during exercise with parasympathetic blockade.
Because this dose is effective for at least 1 h (21),
recovery measurements made during NIPS on session 3 were
also performed during parasympathetic blockade. On a fourth session,
subjects were seated on the bicycle ergometer, but exercise was not
performed. NIPS was performed at baseline and then repeated after
administration of intravenous atropine (0.04 mg/kg).
One subject experienced chest pain after atropine administration during
exercise on the third session, causing cessation of testing. For that
subject, only data from the first two sessions are included in the
analysis. One subject each declined to continue after the first and
third test session. Thus nine subjects completed at least one session
of the protocol. Two sessions were completed by eight subjects, three
sessions by seven subjects, and all four sessions by six subjects.
Noninvasive programmed stimulation.
Before NIPS on session 1, atrial and ventricular pacing
thresholds were measured. All subsequent stimulation was performed at a
fixed output of approximately twice the late diastolic threshold. Rate-responsive features were turned off for the duration of the test.
Lower rate limits and (when possible) paced AV intervals were adjusted
to allow for sinus rhythm with native AV conduction. Each study
consisted of the following.
A 12-lead rhythm strip was recorded for measurement of sinus cycle
length (measured as the mean R-R interval over a 10-s period). Atrial
and ventricular electrograms were recorded when possible through the
device. Atrial pacing was performed with a 12-beat drive train at 500, 400, and 330 ms. The AV interval at these fixed paced cycle lengths was
measured from the onset of the atrial pacing stimulus to the onset of
the QRS complex or ventricular electrogram. The Q-T interval (after the
last paced beat) was also measured at these fixed paced cycle lengths
unless AV block occurred. The Q-T interval could be measured only
during rest and recovery, due to excessive motion artifact during
exercise. The measurement of AV interval and Q-T interval at fixed
cycle lengths allowed for evaluation of the rate-independent effects on
these parameters. The atrial pacing cycle length was then decremented by ~10-ms intervals to determine AV block cycle length, defined as
the longest cycle length that did not result in 1:1 AV conduction. Ventricular effective refractory period was assessed after a 1-min conditioning period in which drive trains of eight stimuli (S1) at the
drive cycle length without an extrastimulus (S2) were applied with
~4-s intertrain pauses (generally related to the delay inherent in
using the pacemaker programmer for NIPS). The ventricular effective refractory period was then measured using the extrastimulus technique, with a drive train of eight stimuli and shortening the extrastimulus by
8- to 10-ms intervals until ventricular capture did not occur or a
minimum coupling interval of 200 ms was reached. The effective refractory period was defined as the longest S1-S2 interval that did
not result in ventricular capture. The minimum S1-S2 interval of 200 ms
precluded assessment of changes in ventricular effective refractory
period in only one subject. Attempts were made to measure ventricular
effective refractory period at drive cycle lengths of 500, 450, and 400 ms so that effective refractory periods were available in each subject
at a particular cycle length for all conditions. The ventricular
effective refractory periods available at the longest cycle length for
all conditions were used for analysis of parasympathetic effect.
At the end of the session, devices were programmed back to pretest settings.
Parasympathetic effect.
Parasympathetic effect on the above parameters at each condition was
defined as the difference in the parameter with and without atropine.
Atropine was given on session 3 during exercise, so measurements made during exercise and recovery on session 3 were in the setting of parasympathetic blockade. The difference between values obtained during exercise and recovery on session 3 and those obtained during exercise and recovery on sessions
1 and 2 defined parasympathetic effect during exercise
and recovery. Atropine was given on session 4 at rest;
therefore, the difference between values obtained after atropine at
session 4 and those obtained at rest preatropine at
session 4 and at sessions 1-3 defined
parasympathetic effect at rest.
Data analysis.
There were up to four baseline and two exercise and recovery
measurements per subject. The reproducibility of these multiple measurements was assessed by linear regression or, in the case of more
than two measurements, by calculating the intraclass correlation coefficient. For the baseline states, the intraclass correlation coefficients were as follows: 0.82 for sinus cycle length, 0.71 for AV
block cycle length, 0.74 for AV interval, 0.81 for Q-T interval, 0.83 for ventricular effective refractory period at 500 ms, and 0.75 for
ventricular effective refractory period at 450 ms. For the exercise
states, regression analysis revealed the following
R2 values: 0.82 for sinus cycle length, 0.73 for
AV block cycle length, 0.62-0.73 for AV interval (at various paced
cycle lengths), and 0.94-0.99 for ventricular effective refractory
period (at various drive cycle lengths). For the recovery states, the
R2 values were 0.73 for sinus cycle length, 0.87 for AV block cycle length, 0.68-0.96 for AV interval (at various
paced cycle lengths), and 0.75-0.89 for ventricular effective
refractory period (at various drive cycle lengths). Thus
electrophysiological data had good-to-excellent reproducibility, and
the results from the multiple sessions were averaged for analysis.
Changes in electrophysiological parameters and parasympathetic effect
among the rest, exercise, and recovery states were assessed with
repeated-measures ANOVA. Pairwise comparisons were performed with
Student's t-test. Parasympathetic effects on different
parameters were correlated using linear regression analysis. All tests
were two-tailed. A P value <0.05 was considered significant.
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RESULTS |
Exercise.
Resting heart rate was 67 ± 11 beats/min; resting systolic and
diastolic blood pressures were 128 ± 17 and 69 ± 11 mmHg.
Subjects exercised for 12 ± 2 (range 7-15) min at a workload
of 70 ± 27 (range 25-100) W. NIPS was performed at 5.5 ± 1.3 min into exercise when the heart rate was 100 ± 9 beats/min. Upon completion of NIPS, heart rate was 107 ± 8 beats/min. At the end of exercise, systolic and diastolic blood
pressures were 165 ± 18 and 77 ± 13 mmHg. During recovery,
NIPS started 1 min after exercise (heart rate was 83 ± 10 beats/min) and was completed by 6.6 ± 1.0 min when the heart rate
was 79 ± 12 beats/min. Systolic and diastolic blood pressures
were 125 ± 20 and 69 ± 9 mmHg after NIPS was completed in recovery.
Electrophysiological changes with exercise and recovery.
The changes in electrophysiological parameters among baseline,
exercise, and recovery states are shown for each parameter in Figs.
1-5.
As expected, sinus cycle length shortened, from 925 ± 157 ms at
rest to 604 ± 56 ms during exercise, and increased to 731 ± 106 ms 1 min in recovery (P < 0.0001 by ANOVA; all
pairwise comparisons, P < 0.005). AV interval at a
paced cycle length of 500 ms was 259 ± 28 ms at rest, shortened
to 217 ± 31 ms during exercise, and increased to 232 ± 29 ms during recovery (P < 0.0001 by ANOVA; pairwise
comparisons significant for baseline vs. exercise, P < 0.0001, and baseline vs. recovery, P = 0.0003). AV
block cycle length was 392 ± 53 ms at rest, 304 ± 37 ms
during exercise, and 338 ± 48 ms during recovery
(P < 0.0001 by ANOVA; all pairwise comparisons,
P < 0.005). Q-T interval, measured at a fixed atrial pacing rate of 500 ms, was 356 ± 23 ms at rest and shortened to 331 ± 18 ms in recovery (P < 0.002 ).
Ventricular effective refractory period at a drive cycle length of 500 ms was 257 ± 19 ms at rest, shortened to 229 ± 16 ms during
exercise, and lengthened to 246 ± 16 ms in recovery
(P < 0.0001 by ANOVA; all pairwise comparisons, P < 0.005).
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Fig. 1.
Sinus cycle length is plotted for all subjects at rest
and during moderate exercise and recovery. Each symbol represents an
individual subject.
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Fig. 2.
Atrioventricular (AV) block cycle length is plotted for
all subjects at rest and during moderate exercise and recovery. Each
symbol represents an individual subject.
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Fig. 3.
AV interval at 500-ms atrial paced cycle length is
plotted for all subjects at rest and during moderate exercise and
recovery. Each symbol represents an individual subject.
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Fig. 4.
Q-T interval at 500-ms atrial paced cycle length is
plotted for all subjects at rest and during recovery. Each symbol
represents an individual subject.
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Fig. 5.
Ventricular effective refractory period (VERP) at 500-ms
drive cycle length is plotted for all subjects at rest and during
moderate exercise and recovery. Each symbol represents an individual
subject.
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Parasympathetic effects.
Parasympathetic effects on all parameters during rest, exercise, and
recovery are shown in Table 2 and Fig.
6. At rest, parasympathetic effects
were noted on the sinus cycle length (247 ± 140 ms,
P < 0.008), AV block cycle length (58 ± 20 ms,
P < 0.003), AV interval (76 ± 20 ms,
P < 0.02), ventricular effective refractory period (8.6 ± 7.5 ms, P < 0.06), and Q-T interval
(17.9 ± 15.9 ms, P < 0.1). During exercise,
there was also significant parasympathetic effect on the sinus cycle
length (106 ± 20 ms, P < 0.0001), AV block cycle
length (37 ± 14 ms, P < 0.001), and AV interval
(24 ± 13 ms, P < 0.007); no significant
parasympathetic effect on ventricular effective refractory period was
noted. During recovery, parasympathetic effects were noted on the sinus
cycle length (209 ± 114 ms, P < 0.003), AV block
cycle length (50 ± 23 ms, P < 0.003), AV
interval (35 ± 21 ms, P < 0.02), ventricular
effective refractory period (9.5 ± 11.8 ms, P < 0.005), and Q-T interval (19.2 ± 14.6 ms, P < 0.02).
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Table 2.
Parasympathetic effects on cardiac electrophysiology at rest, during
moderate exercise, and during recovery
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Fig. 6.
Mean (± SD) parasympathetic effect (in ms) at rest (R), during
exercise (Ex), and during recovery (Rec) on sinus cycle length, AV
block cycle length, AV interval at a paced cycle length of 400 ms, and
VERP. *Significant parasympathetic effect (see Table 2).
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Overall, there was poor correlation between parasympathetic effects on
the sinus and AV nodes, the sinus node and the ventricular effective
refractory period, and the AV node and the ventricular effective
refractory period. There was no correlation between the parasympathetic
effect on sinus cycle length and parasympathetic effect on AV block
cycle length (n = 17, R2 = 0.002, P = 0.84). There was a weakly positive
correlation between parasympathetic effect on sinus cycle length and
parasympathetic effect on ventricular effective refractory period
(n = 17, R2 = 0.30, P = 0.02). Finally, there was no correlation between parasympathetic effect on the AV node and parasympathetic effect on
ventricular effective refractory period (n = 14, R2 = 0.06, P = 0.38).
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DISCUSSION |
This study provides the first comprehensive assessment of cardiac
electrophysiology during exercise and recovery. Moderate exercise is
associated with a shortening of sinus cycle length, AV block cycle
length, AV interval, and ventricular effective refractory period. This
study also provides the first assessment of parasympathetic effects on
cardiac electrophysiology during exercise and recovery. Although
exercise is known to be associated with parasympathetic withdrawal,
there are still measurable parasympathetic effects at the sinus node,
AV node, and ventricle during moderate exercise and recovery.
Parasympathetic effects during exercise are less than those noted at
rest. Parasympathetic effects in the early postexercise recovery period
trend toward the resting values. These data have important implications
on the interaction between exercise, autonomic tone, and the risk for
sudden death.
Exercise is characterized by sympathoexcitation and parasympathetic
withdrawal. Whereas the shortening of sinus cycle length with exercise
is well known, the direct effects of exercise on AV nodal and
ventricular electrophysiology have not been directly measured. The lack
of investigations on electrophysiological changes during exercise
likely stems from the practical difficulties of performing
electrophysiological studies in exercising subjects. The effects of
sympathoexcitation on AV nodal and ventricular electrophysiology have
been studied with catecholamine infusions. In this setting, AV nodal
conduction is enhanced, and there is a decrease in ventricular
refractoriness (4, 8, 24, 25, 40). However, catecholamine
infusion may not be a perfect model for the autonomic changes that
occur with exercise. The relative changes in sympathovagal balance may
differ and may change from exercise to recovery, although both states
are characterized by sympathoexcitation. Robinson et al.
(36) showed that upright tilt and exercise titrated to
produce similar heart rates that were associated with different
autonomic effects. They state "It is thus apparent that achievement
of the same heart rate involved a different balance of autonomic
activity, depending on whether the stimulus was provided by exercise in
supine position or by tilting." The present study provides, to our
knowledge, the first direct electrophysiological data on the AV
node and ventricle during exercise and recovery. During exercise, we
observed marked effects on AV node conduction and ventricular effective
refractory period, which trended toward resting values within minutes
of cessation of exercise.
Parasympathetic effects on cardiac electrophysiology have been studied
by nerve stimulation or pharmacological blockade in resting conditions
(13, 22, 30, 32). Parasympathetic activation prolongs sinus cycle length, AV conduction time, and ventricular refractory period. Our findings that parasympathetic blockade at
rest shortened sinus cycle length, AV block cycle length, AV interval,
Q-T interval, and ventricular effective refractory period are
consistent with these prior data. Previous studies attempting to
evaluate parasympathetic tone during exercise have utilized heart rate
variability. Most (but not all) of these studies demonstrated a
decrease in high-frequency power, felt to be a marker of
parasympathetic modulation, during exercise (3, 26, 29, 37,
38). Generally, no further changes in "parasympathetic"
components of heart rate variability are noted after reaching
50-60% maximal oxygen consumption (26, 37, 38).
Whether this reflects complete parasympathetic withdrawal or withdrawal
to some continual level of parasympathetic effect cannot be ascertained
from these data. The present study documents that there are significant
parasympathetic effects on cardiac electrophysiology during moderate exercise.
The recovery period after exercise is also associated with autonomic
changes. Heart rate is known to decrease and likely reflects both
sympathetic withdrawal and parasympathetic reactivation
(14). Yet, studies of heart rate variability during
recovery provide conflicting results. Compared with exercise,
high-frequency power in recovery has been noted to increase
(3) or decrease (29), although heart rate
variability in recovery has consistently been shown to be diminished
compared with baseline evaluations (1, 3, 29). In this
study, parasympathetic effects were clearly demonstrated in recovery
and were intermediate between those noted at rest and those noted
during exercise.
Parasympathetic innervation of the heart demonstrates regional
differences (34). Vagal preganglionic pathways to the
sinus node are situated in the pulmonary vein fat pad, whereas those supplying the AV node lie in the fat pad overlying entry of the coronary sinus into the inferior interatrial septum. Compared with the
sinus and AV nodes, there are relatively few ganglia found in
ventricular tissues. Parasympathetic nerves are distributed to highly
restricted regions of the heart over discrete anatomical pathways,
which can be selectively altered (33). On the basis of
these differences in innervation, it is reasonable to presume that
parasympathetic effects at these different sites may differ. In fact,
no consistent or strong correlations among the parasympathetic effects
at the sinus node, AV node, or ventricle were noted.
Limitations.
In the present study, the parasympathetic effect was measured as the
difference in the parameter of interest noted in the absence and
presence of parasympathetic blockade. Pharmacological parasympathetic
blockade with atropine has effects on multiple muscarinic receptors.
However, as used in the present study, atropine administration is
considered the gold standard for estimating cardiac vagal tone in
humans (5). It is well known that there may be significant
sympathetic-parasympathetic interactions. These interactions may result
in enhanced parasympathetic effects (17, 22) during
exercise and/or recovery, a phenomenon termed "accentuated antagonism" (17, 19, 20, 25). Nevertheless, the
physiology of interest is the parasympathetic effect that is noted
during exercise and recovery, when there is enhanced sympathetic tone.
The present study also relied on repeated measurements of cardiac
electrophysiological parameters. Day-to-day variability and variability
due to the changing autonomic conditions associated with exercise and
recovery may affect the measurements. Nevertheless, good to excellent
correlation of the multiple measurements was noted.
Because the study protocol required pacemakers or defibrillators, the
subjects do not represent a "normal" population. Most subjects had
at least some degree of conduction system disease. However, attempts
were made to select patients who were not pacemaker dependent; all
subjects had an increase in heart rate with exercise. Although all
subjects had normal left ventricular function, they were not free of
cardiovascular disease and some were taking cardioactive medications.
As previously noted, cardiac parasympathetic effects may be reduced in
individuals with cardiovascular disease. Thus the parasympathetic
effects defined during this study may be an underestimate of the
parasympathetic effect present in a truly normal population. While
medications may alter the autonomic regulation of the heart, all
subjects were on stable doses of medications throughout the study
period. Thus the identified changes in electrophysiological properties
due to parasympathetic blockade do reflect the parasympathetic effects
present in these subjects. It is therefore important to note that this
study provides qualitative (rather than quantitative) evidence
regarding the persistence of parasympathetic effects during exercise
and recovery. It is also likely that the parasympathetic effects are
not exaggerated in the presence of mild conduction system and/or
cardiovascular disease (they are more likely to be understated).
Implications.
There are several important findings related to parasympathetic tone,
exercise, and mortality that highlight the implications of the current
study. There is a large body of work demonstrating that decreased
markers of parasympathetic activity are associated with increased
mortality in patients with cardiovascular disease (6, 16, 18, 28,
31). This epidemiological finding has been shown consistently,
but the pathophysiological link between diminished parasympathetic tone
and increased mortality remains uncertain. It has also been shown that
the risk of sudden cardiac death is increased nearly 17-fold during and
immediately after exercise compared with sedentary periods (2,
23). Recently, abnormal "heart rate recovery" has been
identified as a predictor of mortality (9, 10, 27). A drop
in heart rate of <12 beats/min from peak exercise to 1 min in recovery
was associated with an increased risk of mortality, even after
adjusting for age, sex, risk factors, and medications. These findings
suggest that the autonomic milieu during exercise and recovery may
predispose susceptible patients to sudden death.
One proposed mechanism for the adverse prognosis related to diminished
parasympathetic tone is that the presence of parasympathetic tone
provides cardiac protection. For example, prolongation of ventricular
refractoriness may provide an "antiarrhythmic" effect. We
demonstrated that during moderate exercise in subjects with normal left
ventricular function, there are persistent parasympathetic effects on
cardiac electrophysiology. In subjects with left ventricular dysfunction, there is diminished parasympathetic tone at rest. Exercise
(and recovery) may be associated with further decreases in
parasympathetic tone, thereby increasing the risk of sudden cardiac
death at these times. Further studies investigating the "antiarrhythmic" effect of parasympathetic tone during exercise and
recovery in both normal and diseased populations will provide a better
understanding of the pathophysiological relationship among diminished
parasympathetic tone, exercise, and increased mortality.
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FOOTNOTES |
Address for reprint requests and other correspondence: J. J. Goldberger, Northwestern Univ. Medical Center, 251 E. Huron St., FEIN 8-542, Chicago, IL 60611 (E-mail:
j-goldberger{at}northwestern.edu).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published January 31, 2002;10.1152/ajpheart.00825.2001
Received 19 September 2001; accepted in final form 18 January 2002.
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