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1 Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla 92093; and 2 Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, California 92350
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Exercise-induced arterial
hypoxemia (EIAH) has been reported in male athletes, particularly
during fast-increment treadmill exercise protocols. Recent reports
suggest a higher incidence in women. We hypothesized that 1-min
incremental (fast) running (R) protocols would result in a lower
arterial PO2 (PaO2) than 5-min
increment protocols (slow) or cycling exercise (C) and that women would
experience greater EIAH than previously reported for men. Arterial
blood gases, cardiac output, and metabolic data were obtained in 17 active women [mean maximal O2 uptake
(
O2 max) = 51 ml · kg
1 · min1]. They were studied in
random order (C or R), with a fast
O2 max protocol. After recovery, the
women performed 5 min of exercise at 30, 60, and 90% of
O2 max (slow). One week later, the
other exercise mode (R or C) was similarly studied. There were no
significant differences in O2 max
between R and C. Pulmonary gas exchange was similar at rest, 30%, and
60% of O2 max. At 90% of
O2 max, PaO2 was lower
during R (mean ± SE = 94 ± 2 Torr) than during C
(105 ± 2 Torr, P < 0.0001), as was ventilation
(85.2 ± 3.8 vs. 98.2 ± 4.4 l/min BTPS,
P < 0.0001) and cardiac output (19.1 ± 0.6 vs.
21.1 ± 1.0 l/min, P < 0.001). Arterial
PCO2 (32.0 ± 0.5 vs. 30.0 ± 0.6 Torr,
P < 0.001) and alveolar-arterial O2 difference
(A-aDO2; 22 ± 2 vs. 16 ± 2 Torr,
P < 0.0001) were greater during R. PaO2
and A-aDO2 were similar between slow and fast.
Nadir PaO2 was 
80 Torr in four women (24%) but only
during fast-R. In all subjects, PaO2 at
O2 max was greater than the lower 95%
prediction limit calculated from available data in men
(n = 72 C and 38 R) for both R and C. These data
suggest intrinsic differences in gas exchange between R and C, due
to differences in ventilation and also efficiency of gas exchange. The
PaO2 responses to R and C exercise in our 17 subjects do not differ significantly from those previously observed in men.
arterial blood gases; normal subjects; maximal exercise; acetylene uptake
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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A REDUCTION IN THE EFFICIENCY of pulmonary gas exchange during exercise has been reported many times in the literature (6, 11, 17, 23) and is manifest by an increase in the alveolar-arterial difference of oxygen (A-aDO2) and limited alveolar hyperventilation. Particularly in male athletes capable of high aerobic work, the magnitude of the impairment has been sufficient to cause a reduction in arterial PO2 (PaO2) and hemoglobin O2 saturation (SaO2) (6, 23, 26). This phenomenon, termed exercise-induced arterial hypoxemia (EIAH), defined by some authors as a fall in PaO2 of >10 Torr from resting values (13), offers a potentially significant impairment to aerobic athletic performance (10, 24). Ventilation-perfusion inequality, alveolar-end capillary diffusion limitation, and inadequate hyperventilation have all been proposed as mechanisms for EIAH (15, 26), which affects as many as 50% of the highly aerobic male athletes (23). Typically, the exercise protocol used in studies of EIAH has used treadmill running exercise with rapid workload increments of 1- or 2-min duration.
Women have significantly smaller lung volumes and a lower resting diffusing capacity for CO than men, even when corrected for body size and lower hemoglobin levels (21, 28, 29). A recent study reports a high incidence of EIAH in active women during treadmill exercise with 2.5-min workload increments (13). Of the 29 subjects studied, 22 (76%) experienced EIAH as previously defined.
Studies investigating pulmonary gas exchange during exercise
and using the multiple inert-gas technique, which allows the contribution of ventilation-perfusion inequality and pulmonary diffusion limitation to the A-aDO2, usually use
cycling exercise. This is because of the number and location of
catheters for infusion of the inert gases and the collection of
arterial and pulmonary mixed venous blood. Five-minute work rate
increments are also standard in inert-gas studies because they allow
development of steady-state gas-exchange conditions necessary for inert
gas measurements. A review of data obtained from men undergoing
multiple inert gas elimination studies in our laboratory
(8, 18, 22, 32) indicates that, under these exercise conditions, very few
subjects experience EIAH, even when data from the subjects with the
highest maximal O2 uptake
(O2 max) are considered.
Because of these observations, we hypothesized that
PaO2 would be lower during running than during cycling
exercise, particularly during rapid incremental protocols. In addition,
because of the pulmonary differences previously described, we
hypothesized that PaO2 at a given
O2 max would be less in women than
previously reported in men.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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This study was approved by the Human Subjects Committee of the
University of California, San Diego. Seventeen female subjects (O2 max = 42-61 ml · kg1 · min1) were recruited by
advertisement and, after written informed consent was given, agreed to
further study. All were healthy nonsmokers who exercised regularly and
had a negative medical history. The subjects came from a
variety of athletic backgrounds. Five of the subjects were runners (3 were competing at half-marathon distance), five were triathletes (1 professional and 4 competitive age group triathletes), three were
collegiate soccer players, three were cyclists (including 1 former
world championship medalist), and one was a collegiate swimmer.
Preliminary Screening
A screening history and physical examination were performed; subjects were screened for pulmonary [spirometry, lung CO diffusing capacity (DLCO)] and hematological (hemoglobin, hematocrit) abnormalities. Subjects taking prescription medications, with the exception of oral contraceptives, were excluded. All subjects were screened for pregnancy the day before the start of the study. The following morning, the subjects returned to the laboratory for either the cycle or running test. The order of the two tests was randomized.Subject Preparation
Under continuous electrocardiogram (Lifepak 6, Physio-Control, Redmond, WA) monitoring, a 20-gauge arterial cannula was placed in the radial artery of the nondominant hand, using sterile techniques. A sterile, rapid response (<0.1 s) thermistor (18T, Physitemp Instruments, Clifton, NJ) was placed through the injection hub into the lumen of a small-volume (0.6 ml) extension set with "T" (Abbott Hospitals, North Chicago, IL), which was flushed with saline and connected to the arterial cannula. The thermistor was thus exposed to arterial blood in the cannula when blood was sampled. The peak deflection of the temperature was used as arterial blood temperature (16). Blood was obtained for serum progesterone concentration, which was measured using radioimmunoassay (Diagnostic Products, Los Angeles, CA).Data Collection Protocol
The study took place in two parts. In the first part (fast-increment protocol), the pulmonary gas-exchange responses to either cycling or running exercise were characterized using a standard test ofO2 max with an increase in
workload every minute. Each set of measurements (described below)
consisted of metabolic measurements and a single arterial blood-gas
sample obtained during the last 20 s of each workload.
Cardiac output was obtained using a quasi-steady-state acetylene uptake
method (1) on alternate workloads, to allow for clearance
of recirculating acetylene. Each subject was seated on a bike or on a
chair on the treadmill and breathed through a mouthpiece for 10 min
before the start of the resting measurements. After resting
measurements were obtained, the fast-increment exercise protocol was
started and the subjects exercised to exhaustion. This test was used to
calculate workloads that represented ~30, 60%, and 90% of
the subject's O2 max.
Subjects were then allowed to recover for at least 30 min, after which
the slow-increment protocol was started. This protocol consisted of
5-min increments at workloads producing ~30, 60%, and 90% of
O2 max. Data were collected after 10 min of breathing through the mouthpiece at rest and during the last 2 min at each exercise level. Each set of measurements (described below)
consisted of duplicate arterial blood gases and single metabolic and
cardiac output measurements. The results of the duplicate samples were
averaged (r = 0.91). The following week, the subjects
returned and the study was repeated using the other exercise mode. The
order of the exercise tests was randomized.
Exercise Tests
Cycle ergometer.
O2 max was determined on an
electronically braked cycle ergometer (Excaliber, Quinton Instruments,
Gronigen, Netherlands). After a 5-min warmup at 50 W, the subjects rode
a progressive exercise test (25 W/min) until they were unable to
continue. Heart rate was monitored by a cardiac monitor (Lifepak 6, Physio-Control). The subjects breathed through a non-rebreathing valve
(2700, Hans-Rudolph, Kansas City, MO). Expired gas was sampled
continuously from a heated mixing chamber, and O2 and
CO2 concentrations were measured (mass spectrometer 1100, Perkin-Elmer, Ponoma, CA). Expired gas flow was measured using a
pneumotach (no. 3, Fleisch) and differential pressure transducer
(DP45-14, Validyne, Northridge, CA), and the electrical
signals from the mass spectrometer and the pneumotach were logged at
100 Hz using a 12-bit analog-to-digital converter. Minute ventilation
(E), O2 consumption
(O2), and CO2 production (CO2) were calculated using a
commercially available software package (Consentius Technologies, Salt
Lake City, UT). O2 max was calculated
as the average of the four highest consecutive 15-s measurements of
O2 uptake. All subjects fulfilled at least two of the
following four criteria for O2 max:
1) heart rate 
the age-predicted maximum,
2) respiratory exchange ratio >1.10, 3) no
further increase or a decrease in O2
with increasing workload, and 4) no further increase in
heart rate despite an increase in workload.
Treadmill running.
For resting measurements, subjects were seated on a chair on the
treadmill while breathing through the respiratory circuit as described
above. After resting measurements were made, subjects were allowed to
walk for 5 min at 2.5 miles/h (mph) and 0% grade, and data were
collected in the last minute of this workload. Subjects then warmed up
for 5 min at a treadmill speed of 4.5-5.0 mph and 0% grade, and
data were collected in the last minute of this workload. Next, the
treadmill speed was increased to a comfortable running speed
(determined during a prior visit), which ranged from 5.0 to 7.0 mph.
After 1 min at this speed and 0% grade, the treadmill grade was
increased 2% every minute until volitional fatigue. For the cycling
tests, subjects were allowed to recover for at least 30 min and then
measurements were made at rest and in the last minute of 5 min at 30, 60, and 90% of the previously determined O2 max.
Cardiac Output Measurements
Cardiac output was measured on alternate workloads during the fast incremental protocols and every workload during the slow incremental protocols using an open-circuit acetylene (C2H2) uptake technique (1, 3). The details of this method have been previously reported and show excellent agreement with direct Fick methods for measurement of cardiac output (1). Briefly, at each workload for which cardiac output was measured, subjects were given a gas mixture containing C2H2 (0.5%), helium (1%), O2 (20.9%), and balanced nitrogen to breathe in an open circuit until the helium showed complete mixing plus 12 breaths. Ventilation, end-tidal PCO2, C2H2 partial pressure, and helium partial pressure were measured using a second Perkin-Elmer mass spectrometer. The difference between inspired C2H2 and end-tidal C2H2 (corrected for mixing with the ratio of inspired helium to end-tidal helium) was calculated for each breath. This difference was then extrapolated back to breath 1 to account for C2H2 recirculation. The blood-gas partition coefficient for C2H2 in blood for each subject was measured directly in a standard manner (31). Cardiac output (
T; l/min) was
calculated according to the following equation
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E is the expired ventilation
rate (l/min BTPS),
PECO2 is mixed
expired PCO2,
PACO2 is end-tidal
PCO2,
PIC2H2
is inspired C2H2 partial pressure,
PAC2H2 is end-tidal
C2H2 partial pressure at breath 1 of
the procedure, and 
= C2H2 blood:gas
partition coefficient (BTPS). Cardiac output for
intermediate workloads during the fast incremental protocols was
estimated from the regression of cardiac output and
O2 for each individual subject's
data and each exercise mode (all R > 0.9).
Blood-Gas Measurements
Arterial samples (2 ml) were collected and maintained on ice until analyzed for PO2, PCO2, and pH, using an IL1306 (Instrumentation Laboratories, Lexington, MA) blood-gas analyzer. Hemoglobin and O2 saturation for each sample was measured with an IL482 cooximeter (Instrumentation Laboratories), and hematocrit was determined. The blood gases were measured at 37°C and corrected to measured arterial blood temperature.Statistical Analyses
We made the following statistical comparisons. To compare the effects of exercise mode and work rate, the data corresponding to rest and ~30, 60, and 90% ofO2 max from
the fast increment protocols were selected and compared with the
measured values from the slow-increment protocols. Thus, at the same
relative (and absolute; see RESULTS)
O2, we compared four exercise
conditions: cycle-fast increment, cycle-slow increment, run-fast
increment, and run-slow increment. ANOVA for repeated measures
(SuperANOVA version 1.11, Abacus Concepts, Berkeley, CA) was used to
statistically test changes in the dependent variables between exercise
conditions at each exercise intensity. Preplanned contrasts were used
to compare the changes in the major dependent variables between
exercise mode and ramp increment. In addition, because the lowest
PaO2 for most of the subjects occurred during the
fast-increment running protocol, we examined relationships between the
nadir PaO2 during this protocol and
E, O2 max, cardiac
output, arterial PCO2 (PaCO2),
A-aDO2, and pulmonary function data. Similarly, we examined the relationship between corresponding
A-aDO2 and O2 max, cardiac output, and pulmonary
function data. Significance was accepted at P < 0.05 (two tailed). Data are presented as means ± SE throughout.
We also made comparisons between the PaO2 at
O2 max and data obtained from male
subjects. We collated data from several studies in men that either
cycled (2, 16, 18,
19, 22, 26, 30,
32) or ran (6, 17,
20) at an intensity of 90-100% of
O2 max and developed ±95% prediction
limits for PaO2 as a function of
O2. The limits define the range of predicted values of PaO2 as a function of
O2 max.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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General Data
All subjects tolerated the study well. The subjects were an average of 26.9 ± 1.4 yr old, 165.4 ± 1.3 cm (height), and 58.7 ± 1.1 kg (weight). Pulmonary function data are given in Table 1. All the pulmonary function tests were within normal limits. As we have found for male athletes, on average, forced expiratory volume in 1 s, total lung capacity, and DLCO were greater (9, 9, and 21%, respectively; all P < 0.005) than predicted for normal nonathletic female subjects. However, as expected, vital capacity and spirometry results were less than that predicted for men of similar age and stature. Serum progesterone levels were not different between cycling or running tests (mean ± SE = 1.3 ± 0.5 for cycling, 2.4 ± 1.3 for running; P = 0.3).
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Comparison of Exercise Protocols
Data atO2 max from the two
maximal protocols are presented in Tables
2 and
3. O2 max
was not significantly different between the two exercise protocols and
averaged 50 ml · kg1 · min1
for cycling and 51 ml · kg1 · min1 for running. There were no significant differences
in maximal cardiac output between the two exercise protocols (22.0 ± 0.9 l/min for cycling and 20.8 ± 0.9 l/min for running;
P = 0.16), but heart rate was significantly lower
during cycling than during running (184 ± 2 and 189 ± 2 beats/min, respectively; P < 0.01). Cycling exercise
resulted in greater maximal exercise E (116.2 ± 5.2 l/min BTPS for cycling and 106.6 ± 4.0 l/min
BTPS for running; P < 0.01) and alveolar
ventilation (A; 102.6 ± 4.5 l/min
BTPS for cycling and 92.2 ± 3.6 l/min BTPS
for running; P < 0.05), associated with a
greater tidal volume (VT; 2.90 ± 0.25 liters for
cycling and 2.30 ± 0.13 liters for running; P < 0.05).
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Metabolic and Ventilatory Data
Data obtained at rest and during exercise at ~30, 60, and 90% ofO2 max for each
of the four protocols are presented in Tables 2 and 3.
Subjects had a similar O2 at
rest and during 60 and 90% of
O2 max for the
four different exercise protocols. At 30%
of O2 max,
O2 was significantly
(P < 0.001) lower during the running protocols than
during the cycling protocols; CO2,
E, and cardiac output were also similarly lower.
This was due to the difficulties in matching
O2 with the transition from walking to
running. At 60% of O2 max, there were
no significant differences between the four protocols for
E, A,
CO2, heart rate, or cardiac output.
Respiratory frequency was lower during cycling than during running
(P < 0.0001), VT values were greater
(P < 0.0001), and the dead space-to-VT ratio (VDS/VT) was less (P < 0.005).
At 90% of O2 max, E
and A were significantly (both P < 0.0001) greater in both of the cycling protocols compared with the
running protocols (E = 98.2 ± 4.4 l/min
BTPS for cycling and 85.2 ± 3.8 l/min
BTPS for running). There was no significant difference
between the slow and fast increments. There were no significant
differences in VDS/VT for the four exercise
protocols. Frequency was not different, but VT was larger
during cycling than during running (P < 0.0001); there
was no significant difference between slow and fast increments.
Interestingly, although heart rate was not significantly different
between the four exercise protocols, cardiac output was greater during
cycling exercise than during running (21.0 ± 0.6 and 19.2 ± 0.06 l/min, respectively; P < 0.0005), stroke volume
was larger (P < 0.001), and calculated mixed venous
PO2 was higher (P < 0.0001).
Arterial Blood Gases
At rest and at 30 and 60% ofO2 max, there were no significant
differences between the slow- and fast-increment protocols or cycle and
run protocols for PaO2 or
A-aDO2 (Fig. 1
and Table 2). At rest, PaCO2 was lower in the
slow-increment (P < 0.01) protocols than in the
fast-increment protocols, most likely an ordering effect, since the
slow-increment tests were the second test conducted. Significant
differences were observed between cycling and running protocols at 90%
of O2 max: PaO2 was
greater during cycle than during run (105 ± 2 and 94 ± 2 Torr, respectively; P < 0.0001) associated with both a
smaller A-aDO2 (16 ± 2 vs. 22 ± 2 Torr,
respectively; P < 0.0001) and a lower PaCO2 (30 ± 1 vs. 32 ±1 Torr, respectively,
P < 0.0005). Thus the difference in PaO2
between cycling and running was due to both a difference in efficiency
in gas exchange and a difference in A. In
comparing slow- and fast-increment protocols, there were small but
significant differences between the two work rate increments:
PaO2 was greater during the slow-increment protocol than the during the fast (101 ± 2 and 98 ± 2 Torr,
respectively; P < 0.05), explained by a slightly
smaller A-aDO2 (18 ± 2 vs. 20 ± 2 Torr,
respectively; P < 0.05). There were no significant differences between the two work rate increments for
PaCO2. Consequently, the protocol associated with the
highest PaO2 was the slow-increment cycling protocol
and the one resulting in the lowest PaO2 was the
fast-increment running protocol. Nadir PaO2 values
from the fast cycle and run protocols are shown in Fig.
2. Of the 17 subjects studied, 14 had
lower PaO2 during running than during cycling (P < 0.0005).
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Exercise-Induced Hypoxemia in Female Subjects
We examined the fast-increment treadmill running exercise data for evidence of EIAH. Individual subject data are given in Fig. 3. Our subjects were hyperventilating during the rest period, reflected by lowered PaCO2. This is probably because the resting sample was obtained while the subject sat on a chair placed on the treadmill, anticipating the exercise bout. Because we expected PAO2 and thus PaO2 to be elevated from hyperventilation, we could not use a decrement in PaO2 from the resting data as the criterion for EIAH. Instead, assuming a normal resting PaO2 of ~100 Torr for this population, we defined no EIAH as nadir PaO290 Torr (n = 7, PaO2 = 97 ± 1 Torr), mild EIAH as nadir
PaO2 = 81-89 Torr (n = 6, PaO2 = 86 ± 1 Torr), and severe EIAH
as nadir PaO280 Torr (n = 4, PaO2 = 77 ± 1 Torr). None of the women who
fell into this last category had a similarly low
PaO2 during cycling exercise.
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We used regression analysis to analyze the nadir
PaO2 data (Fig. 4) and
corresponding A-aDO2 data. Nadir
PaO2 during the fast-increment running protocol
was significantly and negatively related to
A-aDO2 (R2 = 0.85, P < 0.0001) and to
O2 (R2 = 0.24, P < 0.05) but not to
PAO2, ventilation, PaCO2,
cardiac index, or any resting test of pulmonary function.
However, A-aDO2 was significantly related to
O2 (R = 0.69, P < 0.005) and cardiac output (R = 0.60, P < 0.05). The PaO2 at
O2 max was closely correlated with the
nadir PaO2 (R2 = 0.86, P < 0.001) but averaged 4 Torr higher than the nadir PaO2 (P < 0.005).
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Gender Effects
We were able to compile arterial blood-gas and metabolic data from 72 male subjects during cycling exercise at 90-100% ofO2 max (2,
16, 18, 19, 22,
26, 30, 32). In these male
subjects, there was a weak but significant relationship between
PaO2 and O2 max
(R = 0.33, P < 0.01). On the basis of
this relationship, we generated a ±95% prediction limit for
PaO2 as a function of
O2 max. Data obtained at
O2 max during the fast-increment
cycling protocol from the present study are compared with data obtained
from 70 men during cycling at 90-100% of
O2 max in Fig.
5. All of the PaO2
values from our female subjects lie above the lower limit of the
analyses as defined for men. A similar analysis for running exercise is also presented in Fig. 5, using data obtained from 38 men
(7, 17, 20). There was a weak
relationship between PaO2 and
O2 max (R = 0.27, P = 0.051). Similar to our results from cycling
exercise, the data from our subjects during running exercise fell above the lower limit of the 95% prediction interval for
PaO2 for men during running exercise.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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In this study of 17 healthy woman, we found significant
differences in PaO2 between running and cycling but
only during very heavy exercise. At 90% of
O2 max, running exercise resulted in a
PaO2 that was lower than for cycling
at the same exercise intensity. Although running resulted in lower
exercise ventilation, less alveolar hyperventilation, and higher
PaCO2, the lower PaO2 was
also related to a greater A-aDO2 during running
than during cycling. Although the effect of work rate increment was
less pronounced, fast incremental protocols resulted in a lower
PaO2 associated with a wider
A-aDO2 without differences in
A. Consequently, on the basis of these findings,
fast-increment running protocols, such as those commonly used with
treadmill O2 max tests, would be most
likely to be associated with significant EIAH.
We were interested in the overall incidence of EIAH and the
gas-exchange response of these healthy female subjects to two types of
maximal exercise. Consequently, we did not confine our data collection
to the midfollicular phase of the menstrual cycle. We chose to collect
data throughout all phases of the menstrual cycle and included women
who were taking oral contraceptives, if they otherwise met the study
criteria. Progesterone is a ventilatory stimulant, and, during the
follicular phase, it is expected that A will be
lower than during the luteal phase. However, progesterone levels were
not different for cycling and running protocols and thus cannot explain
the differences in PaO2 and PaCO2
between the two exercise types.
Cycling Compared With Running
There were no significant differences between cycling and running protocols forO2 max. Generally,
treadmill running protocols are associated with a higher
O2 max than cycle ergometer protocols,
but this difference appears to be minimized in subjects who are
experienced cyclists, as were 12 of our subjects. Maximal cardiac
output values were not significantly different between the two exercise
modes, although heart rate was higher during running exercise. However,
at 90% of O2 max, there was a small
but statistically significant difference in cardiac output between
running and cycling, with the difference being opposite to the expected
direction (running lower than cycling). The reason for the difference
in cardiac output between these two types of exercise at the same
O2 is unknown and has not been
previously reported.
Ventilation.
At 90% of O2 max, ventilation was
greater during the cycling tests than during the running tests, even at
the same absolute O2.
A was also greater during cycling than during running, as was VT. There was no difference in
VDS/VT between the two exercise modalities. As
mentioned earlier, this cannot be explained by menstrual phase
differences. Possibly, pulmonary mechanics may differ between the two
exercise modes. Running is associated with a greater change in
end-expiratory lung volume (EELV) than is cycling, likely because of
increased recruitment of abdominal muscles (14). Although
a lower EELV would be expected to optimize diaphragmatic shortening and
facilitate active expiration, the lung may be displaced to the alinear
portion of the pressure-volume curve and reduce lung compliance
(25). It is also possible that the differences in
ventilation were due to differences in the degree of entrainment
between the two exercise modalities. The extent to which subjects
entrain during different exercise modalities is controversial, but it
is likely that specific training may enhance entrainment during any
given exercise modality (4). Among triathletes,
entrainment is higher during cycling than during running exercise
(5). As mentioned earlier, the majority of the subjects
regularly included some cycle exercise as part of their training
regimen, and it is possible that the extent of entrainment may increase
exercise ventilation at any given workload.
Blood gases.
PaO2 was higher during cycling than during running
exercise partly because of increased ventilation during cycling
exercise compared with running. PaCO2 was lower and
A was higher during cycling than during running
exercise. This is also reflected by the fact that, on average, the
alveolar PO2 was 5 Torr higher during cycling
than during running. These results confirm the results of Gavin and
Stager (9), who demonstrated a lower
SaO2 (measured with ear oximetry)
and lower exercise ventilation during uphill treadmill running compared
with bicycle ergometry in subjects with documented EIAH. However,
averaged over both of the incremental protocols, the
A-aDO2 was 6 Torr greater during running than
during cycling. Possible contributors to the
A-aDO2 results are shunt, pulmonary diffusion
limitation, and ventilation-perfusion inequality. We can only speculate
on the significantly greater A-aDO2 during both
running protocols compared with the cycling protocols, since we did not
directly measure any of these factors. Calculated mixed venous
PO2 was lower during running exercise than
during cycling. Because these were healthy, normal female subjects,
without evidence of heart or lung disease, they were unlikely to have
significant cardiac or pulmonary shunts. In the case of cycling
exercise, the A-aDO2 could be explained by
~1% shunt, but, during running, the shunt would have to be >2% to
account for the blood-gas data. Postpulmonary shunt (from
bronchial and thebesian veins) has been estimated at ~0.2%
(30), and intrapulmonary and cardiac shunts are typically
measured at <0.2% (11, 18,
30). Thus, even given the differences in mixed venous
PO2 between cycling and running, it is
difficult to envision that the amount of shunt would approximately
double between cycling and running. Pulmonary diffusion limitation
could account for the differences in PaO2 between the
two types of exercise, but, because cardiac output was lower during
running than during cycling, one would have to hypothesize either that
pulmonary capillary blood volume was reduced in running compared with
cycling or that the membrane diffusing capacity of the lung was lower;
both explanations appear implausible. Finally, another possible
explanation is differences in ventilation-perfusion matching between
the two exercise types. As noted above, the two different exercise
modalities result in differing EELVs, which in turn may affect
ventilation-perfusion matching.
Slow- Compared with Fast-Increment Protocol
PaO2 was higher and the A-aDO2 was less during the slow-increment protocols compared with the fast-increment protocols. However, the order of the slow- and fast-increment tests was not randomized, and the increase in PaO2 during the second slow-increment test may in part be due to an ordering effect. Repeat exercise has been shown to result in a lower A-aDO2 and a greater PaO2 (12). The mechanism is unknown but may relate to a reduction in pulmonary vascular resistance and improved distribution of blood flow with repeat exercise (33).Exercise-Induced Hypoxemia in Female Subjects
Virtually all of our subjects were hyperventilating at the first preexercise resting sample; thus we could not use a change from resting values to define EIAH. In contrast to the study of Harms et al. (13), which used treadmill exercise and 2.5-min work rate increments, only 24% of our subjects developed severe EIAH compared with 51% of subjects in the Harms et al. study. A major finding of the study by Harms et al. was the occurrence of EIAH in 40% of their subjects with aO2 max that was within
15% of the predicted normal values. In the present study, the four
subjects who experienced severe EIAH all had a
O2 max >50 ml · kg1 · min1 (average 180%
predicted), and there was a significant relationship between nadir
PaO2 and O2 max.
We are unable to explain the differences between our study
and this previous work (13). These differences are not
likely due to different ways of defining EIAH, since the average
PaO2 for our subjects during running
exercise is almost 10 Torr greater and the corresponding
A-aDO2 is 7 Torr less. It is also not due to
differences in aerobic fitness, as
O2 max did not differ significantly
between the two studies (P = 0.2) and the differences
persisted even when subjects of the same
O2 range are considered. One possibility
is the small but significant (P < 0.05) difference in
diffusing capacity between the subjects in the two studies. We are
uncertain why the two study populations should differ in this aspect of
pulmonary function. However, pulmonary diffusing capacity has been
shown to be lower during menses and the midfollicular phase of the
menstrual cycle than during the rest of the menstrual cycle
(27), both in normal menstruating women and in those
taking oral contraceptives. Because the subjects of Harms et al.
(13) were all standardized to the midfollicular phase of
their menstrual cycle and our subjects were studied randomly throughout
the menstrual cycle, this may explain the difference in
DLCO between the two groups of subjects.
Whether the lower diffusing capacity can explain the greater incidence
of EIAH in their subjects is unknown. Perhaps, most importantly, it is
essential to recognize that between these two studies, only 46 women
have been studied in total. In men, the blood-gas response to exercise is remarkably heterogeneous. The two studies likely represent different
parts of the same response spectrum.
As shown in Fig. 5, all of our subjects fell above the 95% prediction
limits for PaO2 as a function of
O2max during both cycling and running
exercise, using published data from healthy normal male subjects. We
were able to compile data from only 38 males during running exercise,
the majority of whom were athletes. Consequently, the mean
O2 max for the male subjects was greater than the mean for our female study population (67 ml · kg1 · min1 in men vs. 51 ml · kg1 · min1 in women), and the
comparison between populations for running exercise must be viewed with
some caution. However, the PaO2 of 15 of the 17 female
subjects lies above the regression line for males. During cycling
exercise, there is considerable overlap between the two study
populations and the mean O2 max values
are similar (53 ml · kg1 · min1 in men vs. 50 ml · kg1 · min1 in women). Thus we cannot conclude that our subjects
are any more susceptible to EIAH than their male counterparts.
Mechanisms of EIAH
In our study, only four subjects developed EIAH; thus conclusions regarding the mechanism are limited. However, we did not find a relationship between PaO2 and PaCO2 in the present study, suggesting that, in our population,A was not a factor explaining the differences
between subjects (although there are clear differences within subjects
for different exercise modes). Rather, there was a close correlation
between the A-aDO2 and PaO2,
suggesting that the efficiency of gas exchange is the major determinant
of arterial oxygenation. At the nadir PaO2, the
corresponding A-aDO2 was significantly related
to cardiac output, suggesting that high pulmonary blood flow may affect
the efficiency of pulmonary gas exchange. We found appreciable EIAH
only during rapid incremental treadmill running. Thus, under conditions
of the same demand for O2, the ability to supply it differs
with differing exercise modalities, and those who do experience EIAH
may not do so under all exercise conditions.
In summary, during heavy exercise, we found significant differences in
arterial oxygenation, ventilation, and efficiency of gas exchange
between running and cycling exercise protocols in fit women. The
reasons for the differences in gas-exchange efficiency are unknown but
may relate to differences in mixed venous O2 content or
ventilation-perfusion matching. We also found a lower incidence of EIAH
in women than found in previous studies (13) and only in
subjects with a O2 max >50 ml · kg1 · min1. The
PaO2 values during maximal exercise in our subjects do
not differ from those previously obtained in males.
| |
ACKNOWLEDGEMENTS |
|---|
We thank Jerome Dempsey and Bruce Johnson for generously sharing original data. We also thank our subjects for enthusiastic participation. The technical assistance of Larry Nava, Rita Klabacha, Nick Busan, and Jeff Struthers is gratefully acknowledged.
| |
FOOTNOTES |
|---|
This work was supported by National Institutes of Health Grants HL-17731, HL-07212, and M01-RR-00827. T. P. Gavin was supported in part by a National Research Service Award HL-09624.
Address for reprint requests and other correspondence: S. R. Hopkins, Dept. of Medicine 0623, Univ. of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0623 (E-mail: shopkins{at}ucsd.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. §1734 solely to indicate this fact.
Received 14 May 1999; accepted in final form 11 January 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
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DISCUSSION
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; n = 17) and for male subjects at
exercise intensities close to or at
;
n = 72 cycling men, 38 running men). A:
cycling results. B: running results. Dotted lines represent
±95% prediction limits for PaO2 as a function of