Download Maximal Heart Rate and Treadmill Performance of

TREADMILL TESTS OF HEALTHY WOMEN/Sheffield et al.
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quantitated treadmill exercise electrocardiograms with arteriographic
location of coronary artery disease. Am J Cardiol 30: 747, 1972
Kaplan MA, Harris CN, Aronow WS, Parker DP, Ellestad MH:
Inability of the submaximal treadmill stress test to predict the location of
coronary disease. Circulation 47: 250, 1973
Robertson D, Kostuk WJ, Ahuja SP: The localization of coronary artery
stenoses by 12 lead ECG response to graded exercise test: support for intercoronary steal. Am Heart J 91: 437, 1976
Goldschlager N, Selzer A, Cohn K: Treadmill stress tests as indicators of
presence and severity of coronary artery disease. Ann Intern Med 85:
277, 1976
Stuart RJ Jr, Ellestad MH: Upsloping S-T segments in exercise stress
testing. Six year follow-up study of 438 patients and correlation with 248
angiograms. Am J Cardiol 37: 19, 1976
Kurita A, Chaitman BR, Bourassa MG: Significance of exercise-induced
junctional depression. Am J Cardiol (in press)
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27. Goldman S, Tselos S, Cohn K: Marked depth of ST-segment depression
during treadmill exercise testing. Indicator of severe coronary artery disease. Chest 69: 729, 1976
28. Cheitlin M, Davia J, DeCastro C, Barrow EA, Anderson WT: Correlation of "critical" left coronary artery lesions with positive submaximal
exercise tests in patients with chest pain. Am Heart J 89: 305, 1975
29. Wagniart P: Problemes particuliers souleves par la comparaison des tests
d'effort et de la coronarographie - Essai de quantification. de l'insuffisance coronaire. In Les 6preuves d'effort en cardiologie, Paris, Sandoz, 1975, p 195
30. Wagniart P, Chaitman BR, Krantz D, Ferguson RJ, Bourassa MG:
Relation entre le moduit frequence - pression A 1'exercice et l'etendue
des obstruction des arteres coronaires. In Les epreuves d'effort en cardiologie. Bourdeaux, Labaz, 1978, in press
31. Ellestad MH, Wan MKC: Predictive implications of stress testing. Circulation 51: 363, 1975
Maximal Heart Rate and Treadmill Performance
of Healthy Women in Relation to Age
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L. THOMAS SHEFFIELD, M.D., JOHN A. MALOOF, M.D.,
JAMES A. SAWYER, M.D., AND DAVID ROITMAN, M.D.
SUMMARY Maximal treadmill exercise heart rate, work
capacity and electrocardiographic response were studied in 95
asymptomatic, predominantly sedentary women between the ages of
19 and 69 years. Average maximal heart rate (MHR) was found inversely related to age, such that MHR = 216 - 0.88 (years of
age) ± 10 beats/min (Xi 1 SD).
Treadmill exercise endurance was 7.64 min ± 1.99. The reduction
of treadmill endurance with advancing age was not statistically
significant.
Asymptomatic ST-segment depression occurred in 6% of subjects.
In 5% the ST segment sloped upward, and in 1% it was flat. Mean age
of women with ST depression was 52 years, compared with 39 years
mean age of all subjects. Premature beats during exercise were
found in 20 of 95 subjects, and were not related to age.
Graded exercise testing of women employing target heart rates
should use heart rate tables developed especially for women. These
tables do not require correction for athletically trained or sedentary
IN ORDER PROPERLY TO EVALUATE the results of
maximal or near maximal treadmill tests for coronary
artery disease or for the quantification of cardiovascular
reserve in valvular heart disease or cardiomyopathies, normal response values are required for comparison. These
reference values should include the maximal treadmill work
capacities of normals, the heart rates attained in performing
maximal exercise and the electrocardiographic responses of
normals to such testing.
Maximal exercise heart rate and work capacity
throughout childhood and adulthood in women and men are
sparsely documented.'-4 Published studies on women have
tended to concentrate on fairly narrow age ranges as in
studies of college students,5' 6 studies limited to individuals
actively engaged in physical education programs,2 or studies
limited to symptomatic patients who should not be classified
as normal.7 One of the largest groups of women was
studied by Cumming and colleagues, 357 women between
the ages of 20 and 83 years.10 However these authors did not
state what evidence they employed to confirm that their subjects were normal, nor was it reported whether the
volunteers were taking any medications at the time of
testing. Only if the range and variability of maximum exercise heart rate in women is known is it possible to apply the
graded exercise test principle appropriately to women, i.e.,
to know with reasonable confidence what level of tachycardia represents 90% of average maximum exercise heart rate
for a given age, in order to recognize when in the course of
an exercise test a near maximal intensity of exercise is taking
place.' Additionally, it would be desirable to establish normal ranges of treadmill exercise endurance with respect to
the age of normal women volunteers.
From the Allison Laboratory of Exercise Electrophysiology, Department
of Medicine, University of Alabama School of Medicine, Birmingham,
Alabama.
Supported in part by Cardiovascular Program Project Grant HE- 11310 of
the National Heart, Lung, and Blood Institute.
Dr. Maloof's present address is 7091 1st Avenue South, Birmingham,
Alabama.
Dr. Sawyer's present address is 509 West Main Street, Dothan, Alabama.
Address for reprints: L. Thomas Sheffield, M.D., Department of Medicine,
University Station, Birmingham, Alabama 35294.
Received April 20, 1977; revision accepted August 22, 1977.
Subjects and Methods
The volunteers studied were 95 asymptomatic women
between the ages of 19 and 69 years. Their mean age was
38.9 years, and there was quite even distribution of their
ages as shown in figure 1. Their mean height was 164.8
cm ± 5.8 (in this and subsequent values, the number
preceding the ± symbol represents the mean; the number
following it, one standard deviation of the mean). Mean
life-style.
CIRCULATION
80
100
90
Is
80
70
t
60
"I
50
.S.
o
s
40
II
a)
I
(L 30
20
4!
10
10
16
22
28
34
28
34
40
46
52
58
64
40
46
52
58
64
70
70
Age, years
FIGURE
1.
Cumulative distribution of subject
age.
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weight was 59.8 + 7.8 kg. Both height and weight values
were also smoothly distributed. Volunteers were recruited
from medical center personnel, local churches and high
school faculties by making general announcements of the
study and the need for subjects. No subject was currently under treatment for an acute illness although three were taking
mild antihypertensive medications. All denied episodic chest
discomfort, palpitation, fainting spells or undue dyspnea on
exertion, and none had been told that she had cardiovascular disease (other than elevated blood pressure). Habitual
physical activity level was assessed by asking whether the
subject engaged in any type of vigorous physical exertion in
sessions lasting at least thirty minutes each, and taking place
at least three times a week. A negative answer was interpreted as indicating athletically untrained or sedentary state.
Physical examination procedure included indirect blood
pressure measurement, peripheral arterial and venous pulse
examination, cardiopulmonary auscultation and examination of the feet and ankles. All blood pressures were between
100 and 160 mm Hg systolic and between 60 and 90 mm Hg
diastolic. No abnormalities of heart, lungs or musculoskeletal systems were noted, and no pitting edema was present. Resting 12 lead ECGs or Frank lead ECGs on all subjects were within normal limits.
The exercise test procedure was explained to each
volunteer. We stressed the importance of keeping us apprised of symptoms when they appeared. Each understood
she was agreeing to continue exercise as long as she could
tolerate doing so; that the experiment would be only as valid
as her conscientious effort to perform maximum exertion.
Each subject was made aware of her right to withdraw her
participation at any moment, and each gave informed consent to be tested. Each subject had the treadmill operation
demonstrated to her, and each familiarized herself with the
treadmill and the other equipment in the laboratory. None
of these women had undergone maximal or near maximal
treadmill exercise testing before.
Continuous heart rate and rhythm monitoring was
provided by the use of an exercise ECG patient cable attached to self-adhering fluid-coupled electrodes on the chest.
The first 51 subjects were monitored by means of Frank
X,Y,Z leads and Wilson V,. On the following 44 subjects a
single bipolar lead, CM-5, which resembles V5, was used.
The ECG was continuously displayed on a multichannel oscilloscope and recorded on magnetic tape. Heart rate was
VOL 57, No 1, JANUARY 1978
monitored with a digital cardiotachometer but the rates
reported here were all measured from ECG strips recorded
at 50 mm/sec at one minute intervals. ECG recorder chart
speed accuracy (± 1%) was reconfirmed at every test.
Treadmill exercise took place in successive uninterrupted
three minute stages at speeds and elevations as follows: stage
1, 2.7 kph, 10% grade; stage 2, 4.0 kph, 12% grade; stage 3,
5.5 kph, 14% grade; stage 4, 6.8 kph, 16% grade; stage 5, 8.0
kph, 18% grade.'1
Treadmill speed (± 2%) and elevation accuracy (± 0.5%
grade) were confirmed before and after the study. The exercise laboratory temperature was maintained between 21 °C
and 23°C.
Exercise was terminated upon request of the subject;
further inquiry determined whether this was because of inability to continue or for a discretionary reason. Exercise
was also terminated if the subject became in need of holding
onto the handrails in order to maintain her position on the
treadmill. Exercise would have been stopped upon recognition of any disorder of cerebral or myocardial perfusion,
blood pressure regulation or neuromuscular coordination,
cardiac rhythm or conduction had any of these occurred.
Observation and recording were continued for six minutes
after exercise with the subject in a sitting position. Blood
pressure was measured indirectly during each stage of exercise and every two minutes after exercise.
Results
All exercise tests herein reported represented convincingly
good effort on the part of each subject. No instances of
hypotension occurred. No tests were interrupted by anyone
other than subjects themselves. No disagreeable side effects
or misadventures were encountered.
These women did not appear to stress themselves as
severely as have men volunteers in similar test situations
participating in maximal exercise studies.4 These subjects
persevered until they had to grasp handrails to stay in place,
or refraining from this actually lost ground. Despite this,
they usually did not develop impressively fast, labored
breathing, cool, clammy skin or staggering gait just before
stopping as had most of our men volunteers.
Treadmill exercise duration ranged from 3.5 min to 12.5
min, mean 7.64 min ± 1.00 SD. Exercise duration was
weakly related to maximum heart rate (r = 0.22) but interestingly the expected inverse relationship to subject age
was insignificant (P = 0.3). None of the other variables we
studied was significantly related to exercise duration. Height
and weight of subject were not related to exercise endurance
or other variables but were related to each other (r = 0.48).
Specifically, there was no established tendency toward increased weight with advancing age.
All heart rate observations were related to subject age and
to each other. Resting heart rate was inversely but weakly
related to age (r = - 0.33). At the end of each 3 min exercise stage the relationship to age strengthened, and at peak
exercise the maximum heart rate showed its closest correlation with age (r = - 0.76). Maximum heart rate in women
may be predicted by the equation, MHR = 216 - 0.88
(years of age) (fig. 2). This prediction has a coefficient of
variation of 5.5% (standard deviation, ± 10 beats/min;
r' = 0.56). No significant relationship was found between
TREADMILL TESTS OF HEALTHY WOMEN/Sheffield
et
al.
81
2401
220
220
200
'
E
**
180
200
160
180
1401
160
120
X0
I
80
@
140
4
120
HR=2 16 -0.88 (age)
+10 b/m (lsd)
R' =0.58
60
40
100
I
80
20
60
10
0
20
40
50
bU
70
.11
80
Age, Years
40
FIGURE 2. Maximum exercise heart rate in relation
to age.
[
20 [
o
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resting heart rate and maximum exercise heart rate. On the
other hand, by adding both resting heart rate and the heart
rate attained at the end of the first 3 minute exercise stage,
approximately 10% improvement in prediction is possible:
MHR = 162 + 0.266 (resting heart rate) + 0.164 (3 min exercise heart rate) -0.70 (age). With this equation the
coefficient of variation is reduced to 5.0% and standard
deviation is reduced to 9 beats/min. (Even this is hardly an
exact prediction, since the 95% confidence limit is ± 18
beats, or a total of 36 beats/min in range.)
The mean heart rate and one standard deviation from the
mean at the end of the first 3 minute stage of exercise is
139 ± 19 beats/min; at the end of the second stage,
165 + 18 beats/min; and at the end of the third stage,
176 + 14 beats/min (fig. 3). Only two women completed the
fourth stage and none completed the fifth or higher stages.
We considered the question whether women with greater
exercise capacity might have a different age regression of
maximum heart rate from that of women with lesser
capacity. Age regressions were calculated separately for
women with above average treadmill exercise durations and
those with below average duration. No significant difference
in the slopes of the regressions was found, and indeed the
two curves were virtually identical. It should be emphasized
that nearly all subjects were classified by us as sedentary
rather than physically trained. It is possible that a different
result would have occurred if the tested population had included an appreciable number of athletes.
In these asymptomatic women heart rate dropped rapidly
following termination of exercise, from a mean MHR of 181
to 145 beats/min after one minute of rest. Deceleration of
heart rate receded in the second minute postexercise by a
mean of 22 beats to 123/min. This trend persisted to the
fourth minute when the mean was 107/min. By this time
heart rate slowing became very gradual; at 6 minutes the
mean heart rate was 102. All postexercise heart rates, as well
as resting and exercise heart rates, clearly had an inverse
relation to age, which diminished slightly in the postexercise period; at stop of exercise r = 0.76; 2 min postexercise, r = 0.61; 4 min postexercise, r =-0.54; 6 min
postexercise, r = 0.48.
We expected women with greatest physical fitness, and
therefore with longest treadmill endurance, would show a
Rest 03
Control
06
09
Exercise
...2
01
-12r
Stop
02
03
04
04
0.
05
06
Post Exercise
FIGURE 3. Mean heart rate and one and two standard deviations
of the mean at rest, at the end of each stage of exercise, and at one
and two minute intervals postexercise.
more rapid deceleration of heart rate after exercise than
those with shorter exercise times. No such correlation with
treadmill exercise time was noted, however.
Electrocardiographic Findings
In this group of asymptomatic women no clinical symptoms or signs suggested the presence of ischemic heart disease during or after the exercise stress. Completely in the
absence of chest pain, however, six of 95 subjects (6%)
developed ST-segment depression which was greater than
0.1 mV at the J point and at least 0.1 mV 80 msec after the J
point* (fig. 4). Five of the six cases were of the slowly ascending ST-segment variety and the remaining one was flat.
The mean age of the women with ST depression was 52
years, and only one was as young as 38. Since the mean age
of all subjects was 39, those with ST depression were notably
older than the average.
Of the six with ST depression, two persons had blood
pressures over 130/84. One was a 60-year-old woman with
blood pressure 160/88, and the other a 59-year-old with
blood pressure 150/90. Neither was receiving antihypertensive therapy.
One-fifth (20 of 95) of the subjects manifested premature
beats during the test (fig. 5). The number of premature beats
from a single subject ranged from one to fifty. One subject
had junctional premature beats, three had atrial premature
beats, and 16 had ventricular premature beats. Of those with
ventricular premature beats, three had a single instance each
of paired multiform premature beats. In all other instances
the premature beats were uniform in contour and coupling
interval, and not encroaching on preceding T waves. In contrast with ST-segment depression, premature beats were not
-
-
-
*Since the beginning of this study Froelicher has shown that lead CM-5 has
about 50% more amplitude sensitivity than Wilson V6.12 Therefore we reexamined all CM-5 recordings to see whether there were any with ST depression whose classification might be changed by this difference in sensitivity.
There were none.
VOL 57, No 1, JANUARY 1978
CIRCULATION
82
.......
...
..
±H± ±H±
4+
FIGURE 4.
concentrated in the older subjects but
throughout the group.
Two examples of slowly ascending ST-segment depression.
were
well distributed
Discussion
Heart Rate Response
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The maximum heart rates found in Astrand's study are
remarkably similar to those we found, and in fact any
difference in age regression of maximum heart rate could be
explained by chance variation (table 1). The two groups are
dissimilar with respect to exercise history. Astrand's subjects were members of a group regularly taking part in
.LLIJ.LLLLL
organized exercise since leaving school. Had these women
participated in our study we would have classified them as
physically trained. Of our 95 volunteers only three fell into
the physically trained category, and the remainder were
classified as sedentary.
These women volunteers did not appear to become as
completely exhausted in the course of performing maximal
exercise tests as men volunteers had become in previous
studies. This observation raised the question whether maximum effort had indeed taken place. At the time of testing
each subject understood the procedure, had been cooperative
and continued exercise until unable to maintain position on
the treadmill without holding on. Wilmore has found that
strong motivation will result in subjects being able to
demonstrate increased power or endurance. However indices
of maximal aerobic capacity such as maximal oxygen consumption or maximal exercise heart rate are not increased
by motivation.'3 He explains that motivation has the power
of increasing the degree of anaerobic metabolism tolerated
by the body, while not affecting maximal aerobic
mechanisms. Our findings are consistent with other studies
in which maximal oxygen consumption was documented by
actual measurement. Therefore we are convinced that the
volunteers we studied actually did perform maximal aerobic
exercise, but that they probably did not force themselves
into anaerobic metabolism at the peak of exercise to the
degree that previous volunteers had done. It should be
remembered, however, that physiologic documentation of
maximal aerobic performance requires measuring a plateau
of oxygen consumption in spite of increasing work output.
We did not monitor oxygen consumption.
Our maximum heart rate results are similar also to those
of Profant and colleagues'4 in comparable age ranges.
By use of the maximum exercise heart rate age regression
found in this study it is possible to construct a graded exercise test target heart rate table for women (table 2), consisting of 90% of the average maximum heart rate found in
each half-decade studied. This table is considerably different
TABLE 1. Reported Average Maximal Exercise Heart Rate
Responses by Decades
Author
FIGURE 5. Premature beats provoked by exercise. Top) Supraventricular premature complex. Middle) Pair of multiform ventricular
premature complexes occurring one minute postexercise. Bottom)
Pair of multiform ventricular premature complexes occurring at
peak exercise, chart speed 50 mm/sec.
Astrand2
Benestad et al.26
Cumming et al.'0
Metheny et al.6
Profant et al.14
Sheffield et al.
Number of
Age range (yr)
subjeots 20-29 30-39 40-49 50-59 60-69 70-79
44
10
357
17
144
95
187 185 178 170
153
197 192 179 167 158 145
197
184 180 177 160
194 186 178 166 165
TREADMILL TESTS OF HEALTHY WOMEN/Sheffield et al.
83
TABLE 2. Graded Exercise Test Target Heart Rates for Women
Age (yr)
Stress level
100% (Max)
90% (GXT)
20
25
30
35
40
45
50
55
60
65
198
179
194
175
190
171
185
167
181
163
177
159
172
155
168
151
163
147
159
143
from the target heart rate values developed for men.15 For
example, at age 60 the target heart rate for women is 13
beats/min lower than that recommended for sedentary men.
As is the case with men, women's target heart rates are for
comparative purposes, to give a general indication as to
whether a test subject has put forth near maximal effort.
Target heart rate should never be misused to prolong an exercise test after a clinically valid reason for stopping has occurred, nor should it be used as the only basis for terminating a test when a subject does not appear adequately
stressed.
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Exercise Capacity
Work capacity is known to be greater in men who engage
in regular strenuous physical activity than in sedentary men
of the same age.4 11,16 This effect has also been observed in
women by Astrand and by Bruce's group.2 14 Nearly all of
our subjects were classified as sedentary, so we had no opportunity to observe the effect of physical training on the exercise capacity of women. However the treadmill performance of our subjects corresponds closely with the sedentary
group reported by Profant et al.'4 and shows lower exercise
capacity than their group of physically active women.
Exercise capacity is known to decline with advancing age
in both men and women.2 14, 7 Our group has found the
effect of age to be much less in asymptomatic women than in
men, however; while the treadmill endurance time was
reduced 10% per decade of age in men, we found a reduction
of only 2% per decade in women under 60. Due to sample
size (less than 30 persons per decade), this regression of exercise capacity with age was statistically insignificant
(P > 0.05), but on the basis of the above and other
studies'8 20 there is good reason to believe the effect of age is
real. Another reason for the small effect of age on exercise
capacity in our subjects probably lies in the study design
itself. Frolicher and colleagues found similar results in
studying 192 special project volunteers at the School of
Aerospace Medicine.21 Although they ranged from 25 to 45
years in age, maximal treadmill endurance time for the older
subjects was the same as that for the younger ones. This consequence of using an asymptomatic volunteer group was anticipated at the outset and accepted, since our aim was not to
study the incidence of disability with age but to characterize
the reactions and capacities of normal, healthy individuals.
We believe the volunteer-preselection effect was also responsible for our finding no relationship between subject body
weight and age. It is known that women's weight increases
with age in the general population (as does men's), and this
was also found in the studies of Astrand, Profant et al. and
Andersen.2 14, 1 One gathers from these studies that the
common trend of aging is to reduce daily physical activity,
gain weight and lose exercise capacity.23 Our study shows
that women who are asymptomatic and consider themselves
in good health may not follow this pattern at all.
Electrocardiographic Observations
Profant et al. reported the incideni e of ST-segment
depression in asymptomatic women to vary from zero in the
third decade to 67% in the seventh. ST deviations were,
however, predominantly of the upsloping variety." Of 144
women tested they observed only two with flat or downsloping ST-segment reaction to exercise. This is comparable to
our finding one such instance in 95 women. In addition,
five of our subjects manifested ST-segment depression of the
upsloping variety.
We found premature beats on exercise in one-fifth of our
subjects, while Astrand found them in nearly half (19 of 44)
of hers.2 When one compares the occurrence of ventricular
premature beats, however, the results are similar: 14% in her
subjects and 16% in ours. Ventricular premature beats are
known to have an adverse prognostic effect in persons with
known coronary heart disease,24' 25 but the significance of
their occurrence in persons with a normal cardiovascular
history is unknown.
Conclusions
Women who continue to consider themselves healthy have
little reduction in exercise capacity with advancing age, and
these women do not tend to become obese. They have a maximum heart rate regression with age that is different from
men's. This should be taken into account when evaluating
results of strenuous exercise tests. If graded exercise tests
are carried out on women using target heart rates, a heart
rate table based specifically on women's exercise response
should be used.
Acknowledgment
The authors are grateful to the ninety-five women who generously agreed to
be the subjects of this study, to the technicians of the Allison Laboratory, to
David Hurst, Ph.D. and Seng-jaw Soong, Ph.D., who performed numerical
analysis of our data, and to Mrs. Florence Driskill and Mrs. Juanita Brasher
who assisted in the preparation of this manuscript.
References
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code" for ECG classification. Adaptation to CR leads and modification
of the code for ECGs recorded during and after exercise. Acta Med
Scand (suppl 481): 3, 1967
2. Astrand I: Aerobic work capacity in men and women with special
reference to age. Acta Physiol Scand 49 (suppl 169): 1, 1960
3. Strandell T: Electrocardiographic findings at rest, during and after exercise in healthy old men compared with young men. Acta Med Scand 174:
479, 1963
4. Lester FM, Sheffield LT, Reeves TJ: Electrocardiographic changes in
clinically normal older men following near maximal and maximal exercise. Circulation 36: 5, 1967
5. Lepeschkin E, Surawicz B: Characteristics of true-positive and falsepositive results of electrocardiographic Master two-step exercise tests. N
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6. Metheny E, Brouha L, Johnson RE, Forbes WH: Some physiologic
responses of women and men to moderate and strenuous exercise: A comparative study. Am J Physiol 137: 318, 1942
7. Sketch MH, Mohiuddin SM, Lynch JD, Zencka AE, Runco V: Significant sex differences in the correlation of electrocardiographic exercise
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CIRCULATION
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8. Linhart JW, Laws JG, Satinsky JD: Maximum treadmill exercise electrocardiography in female patients. Circulation 50: 1173, 1974
9. Barry AJ, Webster GW, Daly JW: Validity and reliability of a multistage
exercise test for older men and women. J Gerontol 24: 284, 1969
10. Cumming GR, Dufresne C, Kich L, Samm J: Exercise electrocardiogram patterns in normal women. Br Heart J 35: 1055, 1973
11. Doan AE, Peterson DR, Blackmon JR, Bruce RA: Myocardial ischemia
after maximal exercise in healthy men. Am Heart J 69: 11, 1965
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MR Jr, Triebwasser JH, Lancaster MC: A comparison of two bipolar exercise electrocardiographic leads to lead V5. Chest 70: 611, 1976
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14. Profant GR, Early RG, Nilson KL, Kusumi F, Hofer V, Bruce RA:
Responses to maximal exercise in healthy middle-aged women. J Appl
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Dis 19: 33, 1976
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17. Andersen KL: Respiratory recovery from muscular exercise of short
duration. Acta Physiol Scand 48 (suppl 168): 1, 1960
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18. Astrand PO: Experimental studies of physical working capacity in relation to sex and age. Copenhagen, Ejnar Munksgaard, 1952, pp 19-20
19. Grimby GN, Nilsson J, Saltin B: Cardiac output during submaximal and
maximal exercise in active middle-aged athletes. J Appl Physiol 21: 1150,
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20. Rodahl K, Astrand PO, Birkhead NC, Hettinger T, Issekutz B Jr, Jones
DM, Weaver R: Physical work capacity. Arch Environ Health 2: 499,
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21. Froelicher VF Jr, Allen M, Lancaster MC: Maximal treadmill testing of
normal USAF aircrewmen. Aerosp Med 45: 310, 1974
22. The Framingham Study: an epidemiological investigation of cardiovascular disease. Bethesda, U.S. National Heart Institute, Sec. 9,
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23. Gwinup G: Effect of exercise alone on the weight of obese women. Arch
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24. Rodstein M, Wolloch L, Gubner RS: Mortality study of the significance
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Alpha and Beta Adrenergic Effects on Human
Atrial Specialized Conducting Fibers
LUC MARY-RABINE, M.D., ALLAN J. HORDOF, M.D., FREDERICK 0. BOWMAN, M.D.,
JAMES R. MALM., M.D., AND MICHAEL R. ROSEN, M.D.
With the technical assistance of Nan E. Perry
SUMMARY We determined the effects of epinephrine on
automaticity and action potential characteristics of right atrial
specialized fibers (RAF) from human atria obtained during cardiac
surgery. RAF were studied with standard microelectrode techniques
during superfusion with Tyrode's solution at 37°C. A biphasic
response to epinephrine was seen, rate slowing at low agonist concentrations and increasing at high concentrations. The epinephrine-induced slowing of spontaneous rate was due to a decrease in the slope
of phase 4 depolarization. At the high epinephrine concentrations
RAF hyperpolarized. The a-adrenergic blocker, phentolamine,
shifted the dose-response curve upward and to the left and enhanced
the hyperpolarization of RAF. The /3 blocker, propranolol, shifted the
curve to the right and decreased the degree of hyperpolarization. Our
study suggests the presence of a and ,B receptors in RAF. The a
response consists of a slowing of rate, the # response of an acceleration of rate and hyperpolarization of RAF.
THE EFFECTS OF ADRENERGIC AMINES on the
electrophysiologic properties of cardiac fibers have been
studied extensively. Both and adrenergic effects on
/ adrenergic.l' 2 In studies of Purkinje fiber automaticity low
a
mammalian Purkinje fibers'
6
and atria7'
8
have been
described. Phenylephrine, primarily an a agonist, prolongs
Purkinje fiber action potential (AP) duration as does
norepinephrine in the presence of propranolol. This action
adrenergic. The A agonist,
has been referred to as
isoproterenol, and norepinephrine in the presence of phentolamine both decrease AP duration, an action referred to as
a
From the Departments of Pharmacology, Surgery, and Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.
Supported in part by USPHS-NHLBI grant HL-12738 and a grant from
the New York Heart Association.
Dr. Mary-Rabine is a fellow of the Fonds National de la Recherche Scientifique Belge.
Address for reprints: Michael R. Rosen, M.D., Department of Pharmacology, Columbia University College of Physicians and Surgeons, 630
West 168th Street, New York, New York 10032.
Received February 17, 1977; revision accepted August 8, 1977.
concentrations of epinephrine have been shown to decrease
spontaneous rate3 4 and K+ uptake,3 5 and high concentrations to increase these variables.3-r The decreases in spontaneous rate and K+ uptake are blocked by phentolamine
and have been interpreted as alpha adrenergic;4 5 the increase in rate is blocked by propranolol and has been interpreted as ,B adrenergic.4 The epinephrine-induced increases
in automaticity have been attributed to a selective effect on
the kinetics of iK2 (pacemaker current), and both epinephrine effects on automaticity and on iK2 are blocked by propranolol.6
Despite these studies of adrenergic effects on mammalian
cardiac fibers no information is yet available concerning the
presence of a and ,B adrenergic receptors in human cardiac
specialized conducting fibers. For this reason we studied the
effects of epinephrine and of a and ,B blockade on human
atrial fibers. We found changes in automaticity consistent
with the presence of a and / receptors.
Maximal heart rate and treadmill performance of healthy women in relation to age.
L T Sheffield, J A Maloof, J A Sawyer and D Roitman
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Circulation. 1978;57:79-84
doi: 10.1161/01.CIR.57.1.79
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