Reduced leg blood flow during dynamic exercise

in older endurance-trained men

DAVID N. PROCTOR, PETER H. SHEN, NIKI M. DIETZ, TAMARA J. EICKHOFF,
LORI A. LAWLER, ETHAN J. EBERSOLD, DARRELL L. LOEFFLER,
AND MICHAEL J. JOYNER
Department of Anesthesiology and General Clinical Research Center,
Mayo Clinic, Rochester, Minnesota 55905
Proctor, David N., Peter H. Shen, Niki M. Dietz,
Tamara J. Eickhoff, Lori A. Lawler, Ethan J. Ebersold,
Darrell L. Loeffler, and Michael J. Joyner. Reduced leg
blood flow during dynamic exercise in older endurancetrained men. J. Appl. Physiol. 85(1): 6875, 1998.It is
currently unclear whether aging alters the perfusion of active
muscles during large-muscle dynamic exercise in humans. To
study this issue, direct measurements of leg blood flow
(femoral vein thermodilution) and systemic arterial pressure
during submaximal cycle ergometry (70, 140, and 210 W)
were compared between six younger (Y; 2230 yr) and six
older (O; 5568 yr) chronically endurance-trained men. Whole
body O2 uptake, ventilation, and arterial and femoral venous
samples for blood-gas, catecholamine, and lactate determinations were also obtained. Training duration (min/day), estimated leg muscle mass (dual-energy X-ray absorptiometry; Y,
21.5 6 1.2 vs. O, 19.9 6 0.9 kg), and blood hemoglobin
concentration (Y, 14.9 6 0.4 vs. O, 14.7 6 0.2 g/dl) did not
significantly differ (P . 0.05) between groups. Leg blood flow,
leg vascular conductance, and femoral venous O2 saturation
were ,2030% lower in the older men at each work rate (all
P , 0.05), despite similar levels of whole body O2 uptake. At
210 W, leg norepinephrine spillover rates and femoral venous
lactate concentrations were more than twofold higher in the
older men. Pulmonary ventilation was also higher in the older
men at 140 (124%) and 210 (139%) W. These results indicate
that leg blood flow and vascular conductance during cycle
ergometer exercise are significantly lower in older endurancetrained men in comparison to their younger counterparts.
The mechanisms responsible for this phenomenon and the
extent to which they operate in other groups of older subjects
deserve further attention.
exercise hyperemia; respiratory muscles; catecholamines;
master athlete

EXERCISE PERFORMANCE declines with advancing age.

Blood flow to active skeletal muscles is a potentially
important factor in the decline in exercise performance
associated with aging (8, 1416, 18). During the performance of small-muscle-mass exercise such as handgripping, active muscle blood flow appears to be well
preserved in healthy older humans (8). Similar findings
have been reported in studies involving single-leg
cycling (3) and unilateral or bilateral isolated knee
extensions (14). However, in each case the size of the
active muscle mass was substantially less than that
recruited during conventional whole body exercise such
as bicycling, walking, or running.
To our knowledge, only one investigation has examined the influence of age on active muscle blood flow
during large-muscle-mass exercise in humans (34). In
that study, Wahren et al. (34) reported that leg blood

68

flow responses during upright leg cycling were 1015%

lower in older endurance-trained men compared with
those reported in an earlier investigation of younger
athletes (10). However, the cardiac output responses of
older and younger endurance athletes at a given sub O2)
maximal power output or whole body O2 uptake (V
appear to be similar (22, 28). This latter finding has
often been interpreted to suggest that even during
large-muscle-mass exercise, blood flow to exercising
muscles should be well maintained with aging (31).
With this information as a background, the present
study was designed to determine whether leg blood flow
and vascular conductance during submaximal, largemuscle-mass exercise are reduced in older vs. younger
humans. To do this, we made direct measurements of
leg blood flow (femoral vein thermodilution) and systemic arterial pressure in younger (2230 yr) and older
(5568 yr) chronically endurance-trained men during
submaximal bouts of two-leg cycle ergometry. Trained
subjects were used rather than sedentary subjects to
ensure that comparisons of leg hemodynamic and metabolic responses between the age groups would not be
confounded by the normal age-related decline in physical activity or by differences in subject motivation and
to ensure that the older subjects could be studied across
a wide range of submaximal power outputs (i.e., at the
same power outputs as the younger subjects). A secondary objective was to determine whether the relation O2, power output, and whole body V O2
ships among leg V
during dynamic exercise in older subjects are similar to
those previously reported in younger subjects (6, 12, 19,
20). Our primary hypothesis was that leg blood flow
and vascular conductance at a given power output
would be lower in the older subjects as a result of
augmented sympathetic restraint of vasodilation in the
active (i.e., leg) muscles.
METHODS

Subject Screening
Six younger (2230 yr) and six older (5568 yr) chronically
endurance-trained men volunteered to participate and completed the study. All were nonsmokers, and none were taking
medications. Their exercise training histories were reviewed
in detail by questionnaire and personal interview. Each of the
subjects was chronically trained and successful in local and
regional competitions, but none were elite-level competitors.
The older men completed a graded treadmill test with 12-lead
electrocardiograph (ECG) and blood pressure monitoring 12
wk before the invasive blood flow study to screen for occult
cardiovascular disease. Overall, the subjects physical charac O2
teristics, training histories, and cycle ergometer peak V

8750-7587/98 $5.00 Copyright r 1998 the American Physiological Society

http://www.jap.org

EXERCISE, LEG BLOOD FLOW, AND AGING

Table 1. Subject characteristics

Age, yr
Height, cm
Weight, kg
Body fat, %
Fat-free mass, kg
Leg muscle, kg
O2 peak , l/min
V
Hemoglobin, g/dl
Training
yr
h/wk
Mode

Younger

Older

27 6 1
181 6 2
72.5 6 3.6
11.5 6 1.3
64.3 6 3.6
21.5 6 1.2
4.28 6 0.24
14.9 6 0.4

63 6 2*
179 6 2
78.5 6 3.3
21.0 6 2.0*
61.8 6 2.2
19.9 6 0.9
3.04 6 0.13*
14.7 6 0.2

12 6 2
761
4 Runners
2 Cyclists

18 6 3
661
4 Runners
2 Cyclists

Values are means 6 SE. Body composition variables were estimated by using dual-energy X-ray absorptiometry. Peak O2 uptake
O2 peak ) was measured during upright cycle ergometry. Hemoglobin
(V
values are for venous blood measured at rest.

O2 peak) levels (Table 1) are similar to those of younger and

(V
older male endurance athletes we recently studied (22). Five
of the 12 subjects (3 older, 2 younger) had served as subjects
in previous studies in our laboratory on related issues (22,
23). Subjects were informed of the risks of the study before
giving written consent in accordance with the Mayo Clinic
Institutional Review Board guidelines.
Subject Preparation
Subjects were instructed to eat a light breakfast (no
caffeine) at least 3 h before arriving at the General Clinical
Research Center on the morning of the leg blood flow studies.
When the subject arrived, a venous blood sample was drawn
to ensure that his hemoglobin concentration was adequate for
repeated blood sampling (i.e., $12.9 g/dl). A dual-energy
X-ray absorptiometry (DEXA) scan was also performed at this
time to estimate the subjects body fat percent and leg (i.e.,
entire lower extremity) muscle mass as described previously
(23).
Catheterization of the femoral vein (for leg blood flow and
venous blood sampling) and radial artery (arterial pressure
and gases) was performed by using aseptic procedures and
local anesthetic. After infiltration of 1% lidocaine into the
right groin, an 18-gauge flexible single-lumen catheter (Cook
royal flush II 4.0-French angiographic catheter) was inserted
just below the right inguinal ligament into the femoral vein
and advanced ,10 cm distally. This infusion catheter was
open ended and had 10 lateral side ports to facilitate mixing
of the iced saline and femoral venous blood (20). A second
18-gauge catheter was then inserted 23 cm below the
inguinal ligament and advanced ,5 cm proximally into the
same femoral vein. A thermister (IT-18, Physitemp Instruments, Clifton, NJ) was subsequently introduced into this
catheter. The catheter was then removed, leaving the thermister in the vein. The infusion catheter and the thermister
were carefully secured into place with adhesive tape. Subsequently, a 20-gauge Teflon catheter (Arrow arterial catheterization set FA-04020) was inserted into the right radial artery
under local anesthesia for arterial pressure measurements
and blood sampling.
Measurements of Leg Blood Flow and Arterial Pressure
The constant infusion thermodilution technique (1, 20, 25)
was used to measure leg blood flow. During exercise, iced
saline (35C) was infused for 1015 s until femoral vein
blood temperature had decreased to a stable level. The rate of

69

saline infusion was adjusted with a roller-pump controller to

achieve an ,1C drop in femoral vein temperature at each
workload. Thermister signals and saline bag weight changes
(Grass displacement transducer FT10C) were displayed on
personal computer-based WinDaq software, which enabled
real-time observation of each measurement. Leg blood flow
was calculated by using the thermal balance equation detailed by Anderson and Saltin (1) and doubled to give two-leg
blood flow (l/min). Simultaneous recordings from the radial
artery pressure transducer (Baxter PX-MK099) were also
displayed and recorded by using WinDaq. The arterial pressure transducer was zeroed at heart level for each subject.
Mean arterial pressure (MAP) represents the true mean of
the arterial waveform, and leg vascular conductance was
calculated as leg blood flow/MAP.
Exercise Protocol
Before exercise, resting blood samples were collected with
the subject supine and also 1015 min after he was positioned
on the bike seat. Exercise was performed on an electronically
braked cycle ergometer (Lode Excalibur Sport) with toe clips,
and the subject was not permitted to lean forward or stand.
After a 5- to 10-min warm-up, subjects completed two continuous, incremental exercise bouts (70, 140, and 210 W, 710
min at each power output). Approximately 15 min of light
pedaling and rest separated the two incremental bouts. These
three power outputs were chosen because preliminary studies
O2 peak),
indicated that these corresponded to light (,40% V
O2 peak), and very heavy (,90% V O2 peak)
moderate (,65% V
workloads in older endurance-trained men. These power
outputs were also within the range of available reference
values for younger male subjects (12, 13, 19, 20) and corre O2 peak), light (,50% V O2 peak),
sponded to very light (,30% V
O2 peak) workloads in younger endurand moderate (,70% V
ance-trained men. A large fan was placed in front of the
subjects, and they were encouraged to drink water between
bouts to ensure that they remained well hydrated.
O2, CO2 production, minute
Pulmonary gas exchange [V
E)] was monitored during the last 34 min of
ventilation (V
each submaximal power output by using an automated
breath-by-breath system (21). Heart rates were measured
with a five-lead ECG (CM-5) during the same time period.
Blood flow and arterial pressure measurements (described in
Measurements of Leg Blood Flow and Arterial Pressure) were
obtained at least three times during each workload (at ,3, 5,
and 7 min), and arterial and deep venous blood samples were
obtained between the second and third flow measurement (at
,56 min).

O2 Calculations
Blood-Gas Measurements and Leg V
The arterial and venous blood-gas samples (3 ml each)
were collected anaerobically in heparinized plastic syringes,
placed on ice, and analyzed within 15 min. Total hemoglobin,
methemoglobin, and percent oxyhemoglobin saturation were
measured by using an AVOX CO-oximeter (model 2000).
Blood PO2, PCO2, and pH were analyzed by using an IL-1620
blood-gas analyzer. All blood-gas measurements were made
at 37C and corrected to the femoral vein blood temperature
obtained immediately before blood sampling (12). Blood O2
content was calculated as [1.39 3 corrected hemoglobin
concentration 3 %O2 saturation] 1 [0.003 3 blood PO2]. Leg
arteriovenous O2 content difference was calculated as the
difference between arterial and venous blood O2 content. Leg
arteriovenous O2 content difference and leg blood flow (2 legs)
O2 (l/min).
were then multiplied to give leg V

70

EXERCISE, LEG BLOOD FLOW, AND AGING

Catecholamines and Lactate

Blood samples for arterial and venous plasma catecholamine concentrations (5 ml each) were measured by using
high-performance liquid chromatography (4). Rate of norepinephrine spillover (net overflow) from the leg was calculated
as described previously (29). Arterial and venous lactate
concentrations (2 ml each) were also measured at each power
output by using a standard enzymatic assay (catalog no.
735-10, Sigma Chemical). Approximately 200250 ml of blood
were collected from each subject over the course of the study.
Statistical Analysis
All data are presented as means 6 SE. Leg blood flow and
other primary-dependent variables (i.e., leg vascular conductance, plasma catecholamines) were reproducible across the
two incremental exercise bouts (intraclass correlations .0.98,
P . 0.05). Therefore, it was decided to combine the data for
the two incremental bouts before age-group comparisons
were made. For most of the age-group comparisons, t-tests
were conducted at each power output (70, 140, and 210 W)
and where possible at baseline. Age-group comparisons at a
given power output, rather than across power outputs (regres O2 at each
sion approach), were justified because whole body V
of these power outputs was essentially identical in the two
age groups (Table 2). The P # 0.05 level was used for all
statistical tests.

E at 140 and 210 W in the older

older men. The higher V
group resulted from their higher breathing frequency.
No significant age differences were seen for heart rate
or MAP.
Leg Blood Flow and Conductance Responses
Reproducibility. Leg blood flow measurements at a
given power output (typically n 5 3/subject) were
highly reproducible, with coefficients of variation averaging between 5 and 7% for both age groups at each
power output (i.e., 70, 140, and 210 W). Mean leg blood
flow and MAP responses at a given power output were
also reproducible across the two incremental exercise
bouts in both age groups (i.e., intraclass correlations
.0.98, P . 0.05). Therefore, it was decided to average
the data for the two incremental bouts before age-group
comparisons were made.
Age effects. At a given power output, absolute leg
blood flow responses were ,2030% lower in the older
men (P , 0.05) during both trials (Fig. 1A). Values
averaged 6.3, 10.2, and 13.2 l/min in the younger men
but only 4.8, 7.5, and 10.2 l/min in the older men at 70,
140, and 210 W, respectively. Similarly, leg vascular
conductances were reduced 2630% in the older vs.
younger men (Fig. 1B).

RESULTS

Blood Measurements (Table 3)

Systemic Responses
Table 2 shows the mean systemic responses to graded
cycle ergometer exercise averaged across the two incre O2
mental bouts. At a given power output, whole body V
was similar between age groups. Respiratory exchange
ratio was similar in both groups except at 210 W, where
E (l/min)
it was higher in the older men. Pulmonary V
was similar between groups at 70 W but was significantly higher at 140 (124%) and 210 W (139%) in the

Table 2. Systemic responses of the younger and older

subjects during graded submaximal cycle ergometry
Power Output, W
Variable

Group

70

140

210

O2 , l/min
V

Younger 1.38 6 0.07 2.10 6 0.06 2.89 6 0.06

Older
1.29 6 0.05 2.02 6 0.04 2.81 6 0.05
RER
Younger 0.85 6 0.05 0.89 6 0.02 0.93 6 0.03
Older
0.85 6 0.01 0.93 6 0.01 1.04 6 0.01*
E, l/min
V
Younger 32.6 6 3.0
48.6 6 4.4
67.9 6 6.6
Older
37.4 6 1.4
63.6 6 2.5* 111.8 6 9.0*
f, breaths/min Younger
21 6 4
24 6 4
27 6 4
Older
28 6 2
32 6 3
42 6 4*
Tidal volume, Younger 1,725 6 240 2,266 6 318 2,670 6 223
ml/breath
Older
1,365 6 70
2,019 6 102 2,694 6 130
HR, beats/min Younger
93 6 3
118 6 5
146 6 6
Older
99 6 5
128 6 6
156 6 7
MAP, mmHg
Younger
99 6 2
106 6 3
113 6 4
Older
106 6 5
114 6 6
124 6 6

Values are means 6 SE for 6 subjects per group and represent

O2 ,
steady-state responses averaged over 2 bouts for each workload. V
E, minute ventilation;
O2 uptake; RER, respiratory exchange ratio; V
f, breathing frequency; HR, heart rate; MAP, mean arterial pressure
measured directly by using radial artery catheter. * Significant
difference vs. the younger group, P # 0.05.

Blood gases. Arterial PO2 along with O2 saturation

and content were maintained across all power outputs
within normal levels in both age groups. By contrast,
femoral vein O2 saturation (Fig. 1C) and content at
each power output were significantly lower in the older
group. Consequently, leg arteriovenous O2 content differences averaged ,2 ml/dl higher (P 5 0.080.11) in
O2
the older group at these power outputs. Mean leg V
responses tended to be lower in the older group (Table
3), but these differences did not reach statistical significance. Arterial PCO2 was maintained at 41 Torr during
all three power outputs in the younger men but fell in
the older men from an average of 37 Torr at 70 W to 33
Torr at 210 W.
Catecholamines and lactate. Baseline levels (i.e.,
seated rest before exercise; data not shown) of arterial
and venous norepinephrine, epinephrine, and lactate
concentrations were similar in the two groups. During
exercise, norepinephrine spillover rates (Fig. 2A) and
venous lactate concentrations (Fig. 2B) were not significantly different between the two age groups except at
210 W, where increases in both variables were larger in
the older men.
DISCUSSION

The primary new finding of this study is that leg

blood flow and vascular conductance during submaximal cycle ergometry are reduced substantially in fit
older men relative to their younger counterparts. These
results are not likely to be confounded by significant
age differences in leg muscle mass, cycling experience,
or arterial O2-carrying capacity, because these variables were similar between these two groups of younger

71

EXERCISE, LEG BLOOD FLOW, AND AGING

and older men. Our findings are unique because they

differ from those reported for exercise involving smaller
muscle masses, where active muscle perfusion appears
to be well preserved up to ,70 yr of age in healthy
subjects (3, 8, 1416).

Table 3. Blood measurements

Power Output, W
Variable

Arterial PO2 , Torr

Group

Younger*
Older
Arterial PCO2 , Torr Younger*
Older
Arterial O2
Younger*
saturation, %
Older
Arterial O2 content, Younger*
ml/dl
Older
Venous PO2 , Torr
Younger
Older
Venous PCO2 , Torr
Younger
Older
Venous O2 saturYounger
ation, %
Older
Venous O2 content, Younger
ml/dl
Older
Arteriovenous O2
Younger
difference, ml/dl
Older
O2 , l/min
Leg V
Younger
Older
Leg O2 extraction, % Younger
Older

70

140

210

100 6 2
92 6 4
41 6 2
37 6 1
97.0 6 0.4
96.5 6 0.4
20.5 6 0.7
20.0 6 0.5
25 6 1
18 6 2
60 6 3
57 6 1
36.7 6 2.7
21.9 6 3.3
7.2 6 0.4
4.4 6 0.7
13.4 6 0.8
15.7 6 0.8
0.94 6 0.14
0.75 6 0.04
65.8 6 2.9
78.1 6 3.4

98 6 4
93 6 5
41 6 2
36 6 1
96.1 6 0.2
95.6 6 0.5
20.3 6 0.8
19.8 6 0.4
25 6 2
19 6 2
64 6 3
62 6 1
31.8 6 2.4
19.7 6 2.1
6.3 6 0.3
3.9 6 0.4
14.0 6 0.8
15.9 6 0.7
1.45 6 0.18
1.19 6 0.06
68.6 6 2.0
80.2 6 2.7

92 6 3
95 6 8
41 6 2
33 6 1
95.4 6 0.5
94.8 6 0.7
20.1 6 1.0
20.7 6 0.5
23 6 1
18 6 1
71 6 5
67 6 2
23.8 6 1.2
16.3 6 1.6
4.9 6 0.2
3.4 6 0.4
15.2 6 0.9
17.4 6 0.7
1.95 6 0.20
1.76 6 0.09
75.5 6 1.3
83.8 6 1.8

Values are means 6 SE for 4 younger and 6 older subjects except

where indicated (*6 subjects) and represent steady-state responses
averaged over 2 bouts for each workload. Arterial and venous
measurements represent radial artery and femoral vein samples,
respectively. All blood gases are corrected for venous blood tempera O2 and O2 extraction are given
ture. Formulas used to compute leg V
in the text. Significant difference vs. younger group, P # 0.05.

Our results quite consistently indicate that the fit

older men studied had ,25% lower leg blood flows at
the three submaximal work rates assessed. Because of
the cross-sectional design of this study, we cannot
entirely rule out the possibility that these age-group
comparisons might reflect genetically influenced adaptations to training in either of the two groups. Differences in skeletal muscle plasticity in response to exercise training at a given age are also a possibility
because the older men were not continuously active in
endurance sports throughout their adulthood (i.e., average age of commencing endurance training was ,45 yr;
Table 1). However, we attempted to minimize these and
other potential influences by recruiting nonelite younger and older subjects with similar endurance training
habits over at least the past 5- to 10-yr period (e.g.,
training mode and hours per week, Table 1). Both
groups of subjects also had similar results in age-group
competitions that placed them in the good but not
elite category. Five of the six older subjects also
indicated involvement in high school and/or college
sports. Thus the question of nature or nurture probably has limited relevance to the findings of this study.
Validity of Leg Blood Flow Results
Fig. 1. Leg blood flow (A), leg vascular conductance (B), and femoral
venous O2 saturation levels (C) in the younger (open bars) and older
(solid bars) groups during leg cycle ergometer exercise at the same
absolute submaximal power outputs. Values are means 6 SE and
represent average responses from the 2 incremental bouts. * Significant age differences at a given power output, P , 0.05.

We are confident that the blood flow differences

detected between these two age groups are valid for the
following reasons. First, before conducting this study
we constructed a hydraulic model to validate our saline
infusion system against volume displacement. Second,
the present in vivo results are based on direct measure-

72

EXERCISE, LEG BLOOD FLOW, AND AGING

Fig. 2. Leg norepinephrine (NE) spillover rates (A) and femoral

venous lactate concentrations (B) in younger (open bars) and older
(solid bars) groups during leg cycle ergometer exercise at the same
absolute submaximal power outputs. Values are means 6 SE and
represent average responses from the 2 incremental bouts. * Significant age differences at a given power output, P , 0.05.

ments of leg blood flow that are highly reproducible in

our laboratory (within-trial coefficient of variation 5
7%). Third, the magnitude of the age difference in this
study is substantially larger than the reported technical variability (,510%) of the technique (12, 13, 20).
Fourth, the blunted leg blood flow response in the older
men was observed during both incremental bouts,
indicating that this is a reproducible difference. Fifth,
O2 of 2.1
blood flow to the legs at 140 W (whole body V
l/min) averaged ,10 l/min in the younger men, which is
nearly identical to values previously reported (19, 32,
O2 values (Table 3) are
34). Finally, our calculated leg V
consistent with what is considered a physiologically
O2; Refs. 19,
valid range (i.e., 6075% of whole body V
20) in the absence of an absolute gold standard for
O2 values for our younger subcomparison. The leg V
jects are nearly identical to values previously reported
(19, 20).

Normal aging is associated with changes in vascular

compliance and possibly other physical properties of
human blood vessels (33). However, we see nothing
about aging per se that invalidates the assumptions of
femoral vein thermodilution for assessing limb blood
flow in healthy older humans. For example, the drop in
blood temperature during the iced-saline infusion period occurs rapidly (510 s) and is primarily dependent
on adequate mixing of saline with blood. In addition,
there are no major age-dependent differences in viscosity (i.e., hematocrit; Ref. 5) or other physical properties
of human blood that would be expected to alter the
specific heat constant (0.92) used in the equation for
calculating blood flow (1). The possibility that atherosclerotic vascular disease might somehow impact thermodilution measurements of leg blood flow is also
remote considering that venous infusion and sampling
were used and that the subject population we studied
consisted of healthy and fit older subjects. Finally, it
should also be noted that Magnusson et al. (14) used
essentially the same technique and reported no ageassociated differences in leg blood flow during smallmuscle-mass exercise (isolated knee extensions).
Our findings are in general agreement with the study
of Wahren et al. (34), who used a different (indocyanine
green dilution) technique to measure leg blood flow
during cycle ergometry in trained 52- to 59-yr-old men.
Their reported age-associated differences in leg blood
flow were 1015% lower in comparison to younger
historical controls (10). As in the present study, they
found significantly larger exercise-induced increases in
femoral arteriovenous O2 difference in the older vs.
younger subjects. This latter measurement provides an
independent indication that leg blood flow is reduced
during cycle ergometry in fit older men.
Potential Mechanisms
The lower absolute levels of leg blood flow in the older
men did not appear to be attributable to a significant
age-associated loss of total limb muscle mass, at least
as estimated by using DEXA. However, it is possible
that an age-related preferential atrophy or loss of
fast-twitch (type II) muscle fibers might alter the
quantity of active muscle or motor unit recruitment
patterns during exercise in humans (2). However, even
in the absence of any age differences in total muscle
mass or insight into muscle recruitment patterns, it
seems reasonable to speculate that the percentage of
leg muscle mass recruited by the older men at a given
work rate was at least the same or higher than it was in
the younger men because of the differences in relative
O2 peak in older men at a
work intensity (i.e., higher %V
given work rate). Collectively, these observations argue
against the possibility that quantity of active muscle
during cycle ergometry is significantly less in fit older
men, at least to the degree that it may explain the large
(i.e., 25%) differences in leg blood flow compared with
younger men having a similar training background.

EXERCISE, LEG BLOOD FLOW, AND AGING

It is also unlikely that the reduced leg blood flows

seen in the older men of the present study can be
attributed to age differences in systemic cardiac output.
This is because we (22) and others (28) have shown that
O2 relationship during submaxithe cardiac output-V
mal cycle ergometry is well maintained with age in
endurance-trained subjects. Additionally, there is no
evidence that maximal vasodilatory capacity of the leg
muscles is reduced in endurance-trained older men.
Martin et al. (15, 16) have reported that the magnitude
of hyperemia after ischemic calf exercise (toe raises) is
the same in endurance-trained younger and older men.
We also observed this in a subset of subjects from the
present study (unpublished observations). These findings are consistent with the observation that capillary
density is similar in the leg muscles of younger and
older endurance-trained men (24). Muscle blood flow is
also reportedly similar in fit younger and older men
during submaximal contractions with small-muscle
groups (14). Finally, blood flow to the legs of the older
men did not appear to be limited by arterial perfusion
pressure because there were no significant age-group
differences in systemic arterial pressure at any of the
three work rates studied. Collectively, these observations indicate that the older subjects had sufficient
muscle mass, cardiac output reserve, and peripheral
vasodilatory capacity to achieve the blood flow values
seen in the younger subjects but that blood flow was
somehow limited in these older subjects during two-leg
cycle ergometry.
The reduced blood flow in the older subjects was
associated with a reduced vascular conductance. These
age differences were roughly the same across the three
workloads studied (all 2030% lower in older men;
Fig. 1B). The blunted vasodilation in these older men
could be due to either reduced vascular responsiveness
to local vasodilator substances or less release of such
substances at a given workload. We have no direct
evidence for either of these possible mechanisms, but
the fall in pH and rise in lactate were much higher in
the older men at 210 W, suggesting an augmented
vasodilatory stimulus at this workload. The increased
norepinephrine spillover in the older subjects at 210 W
raises the possibility that sympathetic restraint of
active muscle blood flow (30) also contributed to the
reduced vasodilation of these subjects at this very
heavy workload.
Finally, it could be argued that the blood flow deficit
seen in the older men is simply an appropriate hemodynamic response given the age difference in relative
exercise intensity. During dynamic exercise, blood pressure and regional vascular resistance (each determinants of organ blood flow) are thought to be regulated
according to the relative, rather than absolute, work
intensity (26). In this regard it is interesting that the
mean levels of MAP were nearly identical in the two
groups when comparisons were made at a similar
relative work intensity (i.e., 210 W for younger vs. 140
O2 peak). However, the leg blood
W for older; ,6570% V
flow values averaged 13.2 l/min in the younger men at
210 W vs. only 7.5 l/min in the older subjects at 140 W.

73

Where is the Extra Blood Flow Going?

As indicated in Potential Mechanisms, we and others
have reported that the absolute level of cardiac output
O2 (#70% of V O2 peak) during
at a given submaximal V
cycle ergometry is well maintained in the older endurance-trained subject. If so, then a significant amount of
flow not reaching the exercising leg muscles must be
distributed to other regional circulations. Saltin (28)
originally raised this question and suggested that older
trained athletes might shunt more blood to the skin.
However, Kenney and co-workers (11) have recently
demonstrated that older fit men actually shunt less
blood flow to the skin during exercise and/or heat stress
compared with younger subjects.
During exercise, visceral blood flow (i.e., renal and
splanchnic circulations) decreases in an intensitydependent manner because of increased sympathetic
nervous activity to this region (26). Ho et al. (7) recently
reported that fit older men shunt less blood flow away
from their splanchnic and kidney circulations than
younger control (i.e., untrained) subjects do during
exercise and/or heat stress. This suggests that fit older
men may experience less visceral vasoconstriction during exercise than younger men do (i.e., less blood is
being shunted away from the visceral organs to the
exercising leg muscles in the older men), even though
venous plasma norepinephrine spillover rates at a
given workload increase with age (17). This could
account for some (perhaps 0.51.0 ml/min; Refs. 7, 11,
28), but not all, of the leg blood flow deficit.
The finding that pulmonary ventilation was significantly higher in the older men at the two highest work
rates suggests that some of the extra blood flow may
be directed to the respiratory muscles. The higher
ventilations seen in the older men at 140 and 210 W
probably result from an age-associated increase in the
dead space-to-tidal volume ratio and increased ventilatory drive associated with greater acidosis at a given
absolute power output. The reduced chest wall compliance of older subjects would also tend to increase their
work of breathing at any given level of ventilation (e.g.,
70 W) (9). The increased demand for respiratory muscle
blood flow in exercising older humans may result in
greater competition between respiratory and locomotor
muscles for blood flow. In this context, the higher
ventilation in the older men at 210 W would conservatively require 200 ml more O2 per minute (see Fig. 5.8 of
Ref. 9). This additional O2 cost would require on the
order of ,11.5 l/min more blood flow (assuming ,6
O2). If anything, these
liters blood flow per liter V
calculations would probably underestimate the extra
blood flow requirements of breathing in older subjects
due to mechanical factors affecting their work of breathing (9).
The existence of such a respiratory muscle steal
phenomenon during exercise has recently been demonstrated in younger male athletes with respiratory
muscle loading and unloading. Harms et al. (6) reported that unloading the respiratory muscles at maximal exercise via proportional-assist ventilation in-

74

EXERCISE, LEG BLOOD FLOW, AND AGING

creased leg blood flow and reduced norepinephrine

spillover in younger trained men, whereas respiratory
muscle loading elicited the opposite responses. However, it is unclear what regulatory mechanism that
governs sympathetic outflow to muscle would be engaged by these maneuvers.
The high ventilatory demands associated with largemuscle-mass exercise could also explain why we observed an age-associated reduction in leg blood flow,
whereas Magnusson et al. (14) did not. In that study,
leg blood flow responses during knee-extensor exercise
were the same in physically active older and younger
men. However, it is likely that the demand for respiratory muscle blood flow is far less during the knee
extension exercise model than it is during conventional
cycle ergometer exercise.
Taken together, a blunted skin blood flow response to
exercise, reduced shunting from visceral organs (e.g.,
0.51.0 l/min), and increased blood flow to respiratory
muscles (e.g., 11.5 l/min) could theoretically account
for a substantial amount of the leg blood flow deficit
seen in the older men in the present study (i.e., 23
l/min).
Summary
The findings of this study demonstrate that perfusion
of the leg muscles during conventional cycle ergometry
is significantly lower in older chronically endurancetrained men in comparison to their younger counterparts. A variety of mechanisms that might be responsible for this observation have also been discussed. The
potential mechanisms responsible for the age-associated differences in leg blood flow observed in fit older
and younger men and their possible impact on muscle
blood flow regulation and exercise tolerance in other
groups of older subjects deserve further investigation.
We thank each subject for enthusiastic participation. We thank
Drs. Peter Wagner, Russell Richardson, and Jerome Dempsey for
their helpful recommendations during the process of setting up the
femoral vein thermodilution technique. We also acknowledge Dr.
John Halliwill for setting up the WinDaq data-acquisition system,
Paul Odenbach for assisting with preparation of tables and figures,
Janet Beckman for secretarial assistance, and Dr. Bruce Johnson for
helpful advice. Finally, we appreciate the efforts of the Mayo Clinic
General Clinical Research Center staff for the screening and follow-up care of our subjects and the General Clinical Research Center
immunochemical core laboratory for performing the blood catecholamine and lactate assays.
This study was supported by National Institutes of Health Grants
HL-46493, NS-32352, RR-00585-25, and RR-00585-24S2 and by the
Glen L. and Lyra M. Ebling Cardiology Research Endowment.
Address for reprint requests: D. N. Proctor, Anesthesia Research,
Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (E-mail:
proctor.david@mayo.edu).

4.

5.
6.

7.
8.
9.
10.
11.

12.

13.

14.
15.
16.

17.

18.
19.

20.

21.

Received 5 November 1997; accepted in final form 10 March 1998.

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