| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Medicine, Division of Physiology, University of California, San Diego, CA, USA2 Department of Anaesthesiology and Critical Care Medicine, Innsbruck Medical School, A-6020 Innsbruck, Austria
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
O2 max (
48 ml kg–1 min–1) during normoxic and hypoxic (inspired PO2= 95 Torr) cycle exercise. Resting lung function was similar between the sexes, except for a lower carbon monoxide diffusing capacity (DLCO) in women (P < 0.05). Arterial PO2,PCO2 and alveolar–arterial O2 difference (A–aDO2) were not significantly different in men and women. Despite a lower diffusing capacity for O2 (DLO2) in women, the ratio DLO2/ß
(which estimates pulmonary end-capillary diffusion equilibrium) was similar between men and women and estimates of diffusion limitation during hypoxic exercise were not different between the sexes. Ventilation–perfusion inequality (described by the second moment of the perfusion distribution, logSD) increased during both normoxic and hypoxic exercise. Surprisingly, logSD values were slightly lower for women under all conditions (P < 0.05), but this did not significantly affect gas exchange. These data indicate that these active women, despite a lower DLCO and DLO2, do not experience greater exercise-induced abnormalities in gas exchange than men matched for age, height, aerobic capacity and lung size. Possibly fitness level and lung size are more important in determining whether or not pulmonary gas exchange impairment occurs during exercise than sex per se.
(Received 14 October 2003;
accepted after revision 22 February 2004;
first published online 27 February 2004)
Corresponding author I. M. Olfert: Department of Medicine 0623A, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0623, USA. Email: molfert{at}ucsd.edu
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
O2 max compared to the O2 max required in men with EIAH (Harms et al. 1998, 2000). For example, EIAH is typically reported only in males with O2 max > 60 ml kg–1 min–1; however, recent studies have found significant EIAH in women with O2 max in the range of 40–55 ml kg–1 min–1 (Harms et al. 1998, 2000).
The potential causes of hypoxaemia during exercise include (1) hypoventilation, (2) O2 diffusion limitation, (3) ventilation/perfusion (A/) mismatching, and (4) pulmonary shunts. While there is evidence that hypoventilation may play an important role in the pulmonary gas exchange impairment in women during exercise, it appears that ventilation alone cannot fully compensate for the excessively widened A–aDO2 (McClaran et al. 1998; Wall et al. 2002). Thus far, however, no studies have attempted to assess the relative contribution of A/ inequality and diffusion limitation to the A–aDO2 during exercise in normal healthy women compared to men. More importantly, there are no studies which compare the effects of sex per se, independent of the effects of lung size on pulmonary gas exchange.
The multiple inert gas elimination technique (MIGET) is a well-characterized method that can be used to partition the contribution of A/ inequality and O2 diffusion limitation to pulmonary gas exchange. While there have been many studies which have used MIGET to investigate gas exchange in normal healthy individuals during exercise (Gledhill et al. 1978; Gale et al. 1985; Torre-Bueno et al. 1985; Hammond et al. 1986a,b; Hopkins et al. 1994, 1998; Rice et al. 1999), these studies have been almost exclusively comprised of male subjects. To our knowledge there have been only two studies which have used the MIGET technique and have also included female subjects (Wagner et al. 1986; Bebout et al. 1989), and in each of these studies there was only one female subject. Consequently, comparisons of pulmonary gas exchange between the sexes using MIGET in normal healthy subjects are very limited.
In light of recent reports suggesting that women may be more susceptible to gas exchange impairment during exercise, we sought to determine whether healthy athletic women would develop greater A/ inequality and/or O2 diffusion limitation during exercise when compared to men. However, because aerobic fitness level and body size, as well as lung size (Hopkins et al. 1998), may also affect pulmonary gas exchange, we matched males to females based on age, height and fitness level (i.e. O2 max), and coincidentally, lung volumes. We exercised men and women in both normoxia and hypoxia to give the best evaluation of the contribution of both A1/ matching and O2 diffusion limitation to pulmonary gas exchange during light, moderate and heavy exercise. We hypothesized that if women experience more disturbance of gas exchange, they would exhibit a greater increase in logSD (defined as the second moment of the perfusion distribution and an index of A/ inequality) and/or a reduced diffusing capacity for O2(DLO2), resulting in a greater A–aDO2 difference and a larger fall in PaO2 with increasing exercise intensity compared to men.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
O2 max, ml kg–1 min–1) of the men matched that of the female group. Preliminary screening and maximal exercise testing
Medical history, physical examination, and screening for cardiovascular (3-lead electrocardiogram during exercise), pulmonary (spirometry, DLCO) and haematological (haemoglobin, haematocrit) abnormalities were performed. Total lung capacity (TLC) was calculated from slow vital capacity (SVC, data not shown) plus residual volume (RV). RV was measured using a standard inert gas dilution method. Percentage body fat and lean body mass (LBM) was determined by hydrostatic underwater weighing. Calculation of body fat percentage (% fat) was made using the Siri formula (Behnke, 1961) and LBM was calculated as the difference between total body mass and fat mass.
Subjects performed two incremental exercise tests to exhaustion, one in normoxia (inspired [O2]= 20.93%, PIO2150 Torr) and another in hypoxia (inspired [O2]= 12.5%, PIO295 Torr) while riding an electronically braked cycle ergometer (Excaliber, Quinton Instruments, Groningen, The Netherlands). Subjects warmed up at 40 W for 5 min, after which the workload was increased in 40 W increments until volitional fatigue. For women, all tests were performed during the follicular phase of their menstrual cycle, which was confirmed by blood progesterone levels (0.6 ± 0.1 ng ml–1 (mean ±S.D.), range 0.5–0.8 ng ml–1). During the exercise test, subjects breathed through a non-rebreathing valve (Hans-Rudolph 2700, Kansas City, MO, USA) while expired gas was continuously sampled from a heated mixing chamber, and O2 and CO2 concentrations were measured using a mass spectrometer (Perkin-Elmer 1100, Pomona, CA, USA). Expired gas flow was measured by using a pneumotach (Fleisch no. 3) and a differential pressure transducer (DP45-14, Validyne, Northridge, CA, USA). Heart rate and rhythm was monitored by cardiac monitor (Lifepak 6, Physio-control, Redmond, WA, USA). Electrical signals from the mass spectrometer and pneumotach were digitally obtained, using a 12-bit analog-to-digital converter set to sample at 100 Hz. Minute ventilation (E), O2 consumption (O2) and CO2 production (CO2) were calculated using a commercially available software package (Consentius Technologies, Salt Lake, UT, USA).
Measurement of cardiac output (T) was made at rest and during each exercise workload using the open-circuit acetylene (C2H2) uptake method (Barker et al. 1999). The blood:gas partition coefficient (
) for C2H2 was determined for each subject using venous blood and gas chromatography (Wagner et al. 1974). Because it was important that mixed venous C2H2 levels return to zero (or very near zero, i.e. <2.5% of inspired C2H2) between successive T measurements to ensure an accurate T measurement, the time spent at steady-state exercise was longer (i.e. 4–5 min) at lower workloads, where E was low, compared to that at higher workloads (i.e. 1.5–2 min), where E was much higher, which returned mixed venous C2H2 levels to baseline faster.
Exercise protocol and data collection
Subjects selected to participate in the study were asked to return to the laboratory on another day to exercise submaximally for 5 min at a light, moderate and heavy (near maximum) workload. The mean percentage O2 max actually performed by the subjects corresponded to 40%, 70% and 96% in normoxia, and 44%, 73% and 97% in hypoxia. Measurements of arterial blood gases, arterial and mixed expired inert gas concentration (described below), and metabolic measurements were made at each workload. Blood and expired gas samples were collected in duplicate at rest and during the last 1–2 min in each exercise workload. This protocol was performed in both normoxia and hypoxia, on the same day, with subjects resting for 50–60 min between exercise bouts. The order in which the tests were performed (i.e. normoxia first or hypoxia first) was determined using an alternating balanced design so that half of the subjects started with normoxia and the other half started with hypoxia. The order in which the tests were performed by each subject remained the same as that performed during preliminary screening.
Multiple inert gas analysis
The multiple inert gas technique was applied in the usual manner (Gale et al. 1985). Briefly, an inert gas solution (containing sulphur hexafluoride, ethane, cyclopropane, enflurane, ether, and acetone) was prepared in sterile 0.9% sodium chloride solution and infused intravenously for 20 min before the collection of resting samples. The rate of inert gas infusion (ml min–1) was set to equal one-quarter of the E (l min–1) expected at each exercise level. The total volume of fluid infused during the course of the study was 500 ml over 2 h, while the total volume of blood drawn from each subject was 200 ml. These amounts are haemodynamically insignificant for exercising athletes. Duplicate samples of mixed expired gas (15 ml) and arterial blood (6 ml) samples were obtained in gas-tight glass syringes. The concentrations of the six inert gases in mixed expired gas and arterial blood were measured using gas chromatography (Hewlett-Packard 5890A, Wilmington, DE, USA) (Wagner et al. 1974). Mixed venous concentrations of inert gases were calculated from the cardiac output (which was determined from the relationship between T and O2 for each subject using data obtained during preliminary O2 max testing) and the measured arterial and mixed expired concentrations by using the Fick principle. A/ distributions were obtained using a least squares best fit regression analysis with enforced smoothing (Evans & Wagner, 1977). We report the first moment (i.e. mean of the distribution) and second moment (i.e. log standard deviation of the distribution, logSD) of the A/ distributions obtained. It should be noted that the indices of A/ heterogeneity, i.e. the second moment of the distribution, termed logSD (blood flow distribution) and logSD. (ventilation distribution), are essentially insensitive to the assumed values of T within the normal physiological range (Wagner et al. 1985). The residual sum of squares (RSS) was used as an indicator of the adequacy of fit of the data to the 50-compartment model.
Arterial sampling and blood gas measurements
Arterial blood was sampled at rest and during exercise from a 20 gauge catheter (Angiocath 20 GA 1.16 IN, Becton-Dickinson, Sandy, UT, USA) inserted in the radial artery. Following collection of 6 ml of arterial blood for inert gas analysis, 2 ml of arterial blood was drawn in a separate heparinized syringe and used for arterial blood gas assessment. A sterile rapid response thermistor (IT-18, Thermalert TH-5, Physitemp, Clifton, NJ, USA) was placed inline with the arterial catheter and the blood temperature recorded during arterial blood sampling. We take the maximum point of deflection of the thermistor during blood withdrawal as the blood temperature. Blood gas samples were debubbled and stored on ice until analysed for PO2, PCO2 and pH using an IL Synthesis45 blood gas analyser (Instrumentation Laboratories, Lexington, MA, USA). All variables were measured at 37°C and corrected to measured arterial blood temperature. However, from previous work, we have found radial arterial blood temperature to be on average 0.5°C lower compared to rectal (i.e. core) temperature obtained during exercise (S.R.H. unpublished observations). Therefore, temperature correction of blood gas values was based on the actual blood temperature measured during arterial sampling corrected by adding 0.5°C. Haemoglobin and O2 saturation were measured using an IL682 co-oximeter (Instrumentation Laboratories). Blood lactate levels were measured using a YSI 2300D Stat Plus blood lactate analyser (Yellow Springs Instrument Co. Inc, Yellow Springs, OH, USA).
Statistical analyses
Data presented are expressed as mean ±S.E.M., unless otherwise noted. Three-factor repeated measures ANOVA (StatView5.0, SAS Institute, Inc., Cary, NC, USA) was used for determination of significant differences in sex, inspired oxygen fraction (FIO2) and exercise. Where significant differences in FIO2 were found, a separate two-factor (sex, exercise) repeated measures ANOVA was performed for both normoxic and hypoxic exercise. Two-tailed unpaired t tests were used to evaluate a subject's anthropomorphic and descriptive characteristics. One-tailed unpaired t tests were used on all pulmonary function and lung volume measures, since it is well recognized that the average values for females are lower than males. In all cases, significance was determined by a P value < 0.05.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Physical attributes and characteristics of male and female subjects are shown in Table 1. According to the study design, the mean age, height and O2 max (ml kg–1 min–1) were not significantly different between male and female subjects (Table 1).
|
|
Metabolic and haemodynamic data
As expected, E and T increased with exercise, but neither E nor T were significantly different between normoxic and hypoxic exercise, indicating good matching of relative normoxic and hypoxic workloads. E (Table 3), as well as E/body surface area (data not shown), tended to be lower in females compared to males, but these differences were not statistically significant. Neither T nor deadspace ventilation (i.e. VD/VT) differed according to the sex of the subjects (Table 3).
|
O2 and CO2 normalized for body mass (Table 3) or lean body mass (data not shown) did not differ significantly between the sexes at either rest or during exercise. The respiratory exchange ratio (RER) was lower in females compared to males during exercise in normoxia, but not hypoxia (Table 3). The ventilatory equivalents for O2(E/O2) and CO2(E/CO2) did not differ according to the sex of the subject, but as expected were altered by both FIO2 and exercise (data not shown). Circulating lactate levels increased with exercise intensity in both males and females (P < 0.01); however, at the same relative exercise intensity, blood lactate levels were not different between FIO2 conditions, again indicating a good matching of relative workloads. During exercise, in both normoxia and hypoxia, females had lower blood lactate levels than males (P < 0.01, Table 3).
Arterial blood gases and alveolar–arterial O2 difference (A–aDO2)
In both males and females, PaO2 remained largely unchanged (compared to rest) during normoxic exercise (Fig. 1), but was significantly decreased during hypoxic exercise (P < 0.01, Fig. 2). Arterial oxygen saturation (SaO2) decreased during both normoxic (Fig. 1) and hypoxic (Fig. 2) exercise; however, the fall in SaO2 was greater during hypoxic exercise. Although PaCO2 tended to be slightly lower in females compared to males, during both normoxic (Fig. 1) and hypoxic (Fig. 2) exercise, this was not significant. No significant differences between the sexes in PaO2, SaO2, or pH were observed during either normoxic or hypoxic exercise. Whether in normoxia or hypoxia, alveolar PO2 (PaO2) increased with exercise intensity (P < 0.05), but the degree to which A–aDO2 widened during exercise was much greater in hypoxia than in normoxia (P < 0.05, Figs 1 and 2). However, no significant differences in A–aDO2 were observed between the sexes.
|
|
The distributions of ventilation () and perfusion () obtained via MIGET were uniform and unimodal (data not shown). As expected, the first moment of the distributions (mean of and , respectively) increased from rest to heavy exercise (P < 0.001), but no differences between the sexes were observed (Table 4). Averaged over both normoxic and hypoxic exercise and across males and females, A/ inequality as indicated by logSD increased with exercise (P < 0.05, Table 4). However, at all levels of exercise, logSD and logSD values in females were lower than in males by an average of 17% and 11%, respectively (P < 0.05, Table 4). The extent that A/ inequality and intrapulmonary shunt contribute to the A–aDO2 can be estimated by comparing the observed A–aDO2 (A–aDO2(o)) to the predicted A–aDO2 (A–aDO2(p)) that is calculated from the inert gas data. If A–aDO2(o) exceeds A–aDO2(p), the resulting difference, A–aDO2(o – p), can be attributed to diffusion limitation or extrapulmonary shunting. If, on the other hand, A–aDO2(o) does not exceed A–aDO2(p), the cause of this difference can be attributed to A/ inequality and/or intrapulmonary shunt. Physiologically speaking A–aDO2(p) cannot exceed A–aDO2(o), but in normoxia we find that A–aDO2(p) is greater than A–aDO2(o) and results in a negative A–aDO2(o – p). In part, this results from random errors in calculating A–aDO2(o). For example, at an O2 consumption of 2 l min–1, a 5% uncertainty in O2 (± 0.1 l min–1) can result in a negative A–aDO2(o). In contrast, the inert gas prediction of A–aDO2(p) is mathematically constrained to be greater than zero. Thus, the difference between A–aDO2(o) and A–aDO2(p) may be underestimated which leads to a negative bias with respect to A–aDO2(o – p). Adding to this is the potential of any random errors in the estimation of A/ obtained from MIGET; thus it is possible that the A–aDO2(o – p) underestimates the extent of diffusion limitation and/or extrapulmonary shunt.
|
Diffusing capacity for oxygen (DLO2)
Using Bohr integration it is possible to estimate the diffusing capacity for oxygen (DLO2) (Hammond & Hempleman, 1987). By definition our estimate of DLO2 can only be calculated when there is measurable diffusion limitation as evidenced by the measured PaO2 being less than the PaO2 predicted by the inert gases. Since the measured PaO2 was not less than the predicted PaO2 at rest (in both normoxia and hypoxia), and during light and moderate exercise in normoxia, DLO2 cannot be calculated under these conditions. However, during heavy exercise (> 90% of O2 max) in normoxia, diffusion limitation occurred in nine (5 females and 4 males) of the 14 subjects, allowing estimation of DLO2 in those nine subjects. By contrast, during hypoxic exercise, diffusion limitation developed in all subjects, at all levels of exercise, and therefore an estimation of DLO2 could be obtained for all subjects at all levels of exercise (Table 4). Comparing DLO2 during heavy exercise in both normoxia and hypoxia revealed a significant difference between the sexes, where DLO2 was lower in females than males (P < 0.05, Table 4).
Since diffusion equilibrium is suggested to depend on the ratio of DLO2 to the product of T and ß (where ß is the linearized approximation to the O2 dissociation curve; Piiper & Scheid, 1980), we calculated ß using our estimates of DLO2 and T in order to assess pulmonary end-capillary O2 diffusion equilibrium. There was no difference in mean DLO2/ß between male and female subjects during heavy exercise in either normoxia or hypoxia (Table 4) because ß, which is proportional to the haemoglobin (Hb) concentration, was less in women. Thus, although our derived estimates of DLO2 were decreased in women compared to men, these data suggest that the pulmonary end-capillary O2 diffusion equilibrium is not different between the the sexes.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
A/ inhomogeneity or diffusion limitation, even when they exercised in hypoxia. To our surprise, the women in our study exhibited slightly better A/ matching than did men under all exercise conditions. Subject selection and assessing pulmonary gas exchange impairment
It is widely recognized that physical and exercise performance attributes are different between males and females. Because fitness level (Dempsey et al. 1984; Dempsey & Wagner, 1999) has been shown to correlate with impairment in gas exchange, our subjects were matched not only for age and height, but also aerobic capacity, i.e. O2 max (Table 1), thereby eliminating two potential confounding effects of sex differences on pulmonary gas exchange. In our study LBM was determined as the difference between total body mass and fat mass, where fat mass (or percentage body fat) was obtained using the well-established 2-compartment model of hydrodensitometry (i.e. hydrostatic underwater weighing). It should be noted, however, that the reliance on body density alone to measure body fat can result in errors between 2 and 5% in athletes compared to non-athletes, and sex differences may result in errors that may be larger in men compared to women (Prior et al. 2001). Thus, this must be kept in mind when interpreting the results relative to body composition. It should also be noted that, although we did not match our subjects according to pulmonary function and lung size, this was not different between the sexes (Table 2).
Despite the moderate fitness level of our subjects (mean O2 max of 47 ml kg–1 min–1, but ranging from 39 to 57 ml kg–1 min–1) this was sufficient to generate some gas exchange impairment with exercise. Indeed, recent evidence suggests that EIAH may occur in up to 40% of habitually active women with O2 max < 50 ml kg–1 min–1 (Harms et al. 1998, 2000), which, in part, has lead to the notion that women may be more susceptible to gas exchange impairment during exercise than men. Accordingly, we chose to test active women whose O2 max fell within this 40–55 ml kg–1 min–1 range and compared them to similar age-, height-, and aerobic capacity-matched males. Another issue that may be important in determining the level of gas exchange impairment occurring during exercise is the mode of exercise. Treadmill exercise, in particular, is thought to result in greater and more consistent hypoxaemia, which may partly be due to the lower maximal ventilatory response seen with treadmill exercise compared to cycling exercise (Dempsey & Wagner, 1999) and a greater A–aDO2 (Hopkins et al. 2000). In this study, we preferred cycle ergometry over treadmill running because it would allow better comparison of MIGET data to previous studies, which have largely used cycle ergometry to assess pulmonary gas exchange during exercise.
In this study, as before (Rice et al. 1999; Hopkins et al. 2000), we have corrected the blood gas values based on the measured arterial blood temperature obtained during blood gas sampling. All samples were obtained through the radial artery cannula with the tip of the thermistor contained within the cannula, which is in the radial artery of the subject. This is the same type of thermistor that is used for leg blood flow studies using thermodilution. It has a very rapid response (t < 0.1 s) and is highly accurate (varies less than ± 0.1°C compared to a mercury thermometer in post study ex vivo calibration). It is likely that the temperature of flowing blood at the radial artery is less than that at the aorta or pulmonary artery. Indeed, it could not be higher. In fact, previous evidence (S.R.H. unpublished observations) comparing rectal temperature during a slow incremental exercise protocol, which favours temperature equilibrium between measurement sites, resulted in a mean difference of 0.5°C. Thus we have corrected for this discrepancy. However, it should be noted that any underestimation of blood temperature would tend to bias the data towards undercorrecting arterial PO2 values, and lower reported PaO2 values that were actually present, since arterial blood temperature could only be underestimated.
A/ inhomogeneity
In previous studies, A/ inequality has been shown to increase with exercise (Gledhill et al. 1978; Gale et al. 1985) and may be responsible for as much as 60% of the A–aDO2 observed in athletic men (Hopkins et al. 1994). In the present study, logSD also increased with exercise in both men and women exercising under normoxic and hypoxic conditions (Table 4). However, when comparing the sexes, we were surprised to find logSD was lower in females, indicating better A/ matching (Table 4). The small difference in logSD seen between the sexes was not sufficient to significantly affect arterial PO2. It does, however, explain the small, albeit not statistically significant, sex difference in the observed A–aDO2(Figs 1 and 2).
A mechanism by which A/ matching may actually be better in women compared to men is at present unclear. The technical quality of the inert gas data in this study was excellent as evidenced by the low residual sum of squares (Table 4). Coupled with the close agreement of the male data in this study with those of previous studies gives confidence in the results. However, due to a lack of MIGET data in normal healthy women, it is difficult to know whether our data are representative of females in general, or whether they reflect an unusual group of women. The A–aDO2 values we report are smaller compared to other studies (Dempsey et al. 1984; Wagner et al. 1986; Rice et al. 1999), which may suggest that our study population may not be representative of the population at large. Because the pulmonary function of our female subjects was, in general, >110% of predicted (Table 2), it is possible these data may reflect a population bias, e.g. athletic females with relatively large lungs. But whether or not women are more generally found to have better A/ matching during exercise will require additional studies which should include more women with a wider range of aerobic capacity.
O2 diffusion limitation
Previous studies have reported that substantial O2 diffusion limitation is evident during heavy normoxic exercise (Hammond et al. 1986a; Wagner et al. 1986; Hopkins et al. 1994). In this study, evidence of O2 diffusion limitation during normoxic exercise was only seen during heavy exercise (as seen by a positive A–aDO2(o – p) value, Table 4) and the lack of a significant decrease in either PaO2 or SaO2 argues against the presence of substantial O2 diffusion limitation during normoxic exercise. In contrast, all subjects experienced a decrease in PaO2 along with a widening A–aDO2 during hypoxic (PIO295 Torr) exercise (Fig. 2). Previous studies have reported that even light physical activity under hypoxic conditions results in O2 diffusion limitation, and the severity increases with increasing exercise intensity (Torre-Bueno et al. 1985; Hammond et al. 1986b; Wagner et al. 1986). At even moderate altitudes (1000–1500 m), a reduced O2 max and a markedly worse EIAH occur during exercise in highly fit males (Dempsey et al. 1984; Gore et al. 1997). Thus, it could be argued that the lower DLCO measured in females compared to males may predispose women to O2 diffusion limitation, especially during times of high demand on the pulmonary system, such as that during hypoxic exercise. However, it is interesting to note that DLCO in women can vary significantly (up to 13%) during the menstrual cycle with the highest values occurring just prior to menses and the lowest on the third day of menses (Sansores et al. 1995). Because in our study women were tested during the follicular phase of their menstrual cycle (up to 10 days post menses), it is possible that the DLCO values we report represent the lowest end of the range measured during the menstrual cycle. Therefore, it may be difficult to compare DLCO between the sexes. However, consistent with a lower DLCO, women were also found to have lower DLO2 compared to men, but in terms of gas exchange this did not result in a significantly greater A–aDO2 or A–aDO2(o – p). This can be explained by the fact that end-capillary diffusion equilibrium has been shown to depend on the relationship of DLO2/ß rather than DLO2 alone (Piiper & Scheid, 1980). The fact that both DLO2 and ß (due to lower Hb concentration) were lower in women, while T was not different between the sexes, resulted in a similar DLO2/ß ratio between males and females (Table 4) and thus no differences in O2 diffusion limitation are expected. The MIGET technique is not able to differentiate the relative contributions of pulmonary O2 diffusion limitation and extrapulmonary shunting (e.g. from bronchial and thebesian veins) towards the overall A–aDO2(o – p), thus we cannot dismiss the possibility that extrapulmonary shunting may also have contributed to the increase in A–aDO2. In healthy subjects, pulmonary shunting at rest via the bronchial and thebesian veins is believed to comprise <2% of total T (Torre-Bueno et al. 1985; Hammond et al. 1986b; Wagner et al. 1986). In our study, the change in PaO2 during heavy exercise (>90% of O2 max) in normoxia is equivalent to an 1% shunt, and therefore could account for all of the A–aDO2(o – p) we observed during normoxic exercise. In hypoxia, however, an extrapulmonary shunt in the range of 13–16% of T would have been necessary to account for the A–aDO2(o – p) we observed. Given that it is highly unlikely that such a shunt would develop in normal healthy young subjects, we reasoned that pulmonary O2 diffusion limitation is the primary component contributing to the increasing A–aDO2(o – p) during hypoxic exercise and that extrapulmonary shunting contributes a very small component to the overall A–aDO2(o – p).
Mechanical constraints on ventilation, e.g. expiratory flow limitation, can also affect pulmonary gas exchange and may be especially important in women, due to their relatively smaller lung size compared to men. Because we did not directly address this issue, as has previously been done by others (McClaran et al. 1998; Dempsey & Wagner, 1999), we cannot comment on the presence or absence of mechanical constraint. However, since female lung volumes and pulmonary function were not significantly different to males at rest (Table 2), and more importantly, PaCO2 levels (Figs 1 and 2) and EversusO2 (Fig. 3) during exercise were not significantly different, this would suggest that sex-related alterations in alveolar ventilation and/or expiratory flow limitation did not play a role in altering gas exchange in our population of subjects.
|
O2 in ml kg–1 min–1), it is likely that we didn't find significant differences in pulmonary function and lung volumes because of a bias towards athletic women (with larger than predicted lungs) compared to less athletic men (with normal size lungs). This is supported by the observation that pulmonary function in our women was typically > 110% of predicted, whereas the percentage predicted of males was somewhat less (Table 2). Interestingly, when predicted pulmonary function values were obtained using our female subjects' anthropometric data in the male prediction equation, these values were found at or near 100% of predicted (Table 2). The fact that the women in our study, with larger lungs (compared to that predicted for the general female population), did not experience greater gas exchange derangement than men during exercise, might suggest that the susceptibility for EIAH may not be greater in women per se. But, rather that habitually active males or females with relatively small lungs will develop greater pulmonary gas exchange impairment compared to age- and activity-matched counterparts with larger lungs. This is supported by evidence from a previous study involving competitive male cyclists and triathletes, where an increase in logSD is found to occur with decreasing TLC normalized to body surface area (Hopkins et al. 1998). Moreover, the observation that the incidence of high altitude pulmonary oedema may also be related to lung size (in conjunction with the rate of ascent and the degree of physical effort; Cremona et al. 2002), also tends to support the contention that absolute lung size is important in the susceptibility to pulmonary gas exchange impairment during periods of heavy physical activity. But, it should also be noted, other studies examining the relationships between pulmonary function and lung size have shown them not to be related (Mead, 1980; Thurlbeck, 1982). These studies, however, have assessed measures primarily related to lung mechanics (i.e. maximal flow, static recoil and vital capacity). Harms et al. (1998) found no relationship between lung volume and gas exchange when comparing A–aDO2 at O2 max against resting DLCO in a heterogeneous population of women. But, because exercise can alter DLCO (increase due to greater pulmonary capillary blood volume), it is possible that this relationship may be different during exercise. Thus this issue remains unresolved.
In summary, these data show that when men and women were matched for age, body and lung size, and aerobic capacity (O2 max normalized to body mass), exercise did not result in differences in A–aDO2 based on sex. To our surprise, these data revealed less A/ inequality during exercise in female compared to male subjects; however, based on the lack of MIGET data in women and the relatively small sample size in our study, whether or not this observation will persist among women over a wider range in aerobic capacity remains to be determined. The fact that the women in this study (whose pulmonary function and lung sizes were similar to the men) did not experience greater O2 diffusion limitation during exercise, may suggest the importance of absolute lung size or aerobic fitness in determining susceptibility to EIAH and/or gas exchange impairment rather than sex per se.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Bebout D, Story D, Roca J, Hogan M, Poole D, Gonzalez-Camarena R, Ueno O, Haab P & Wagner P (1989). Effects of altitude acclimatization on pulmonary gas exchange during exercise. J Appl Physiol 67, 2286–2295.
Behnke AR (1961). Comment on the determination of whole body density and a resume of body composition data. In Techniques for measuring body composition. ed. Bro
ek J & Henschel JB, pp. 118–133.
National Academy of Science, National Research Council
Washington,
DC.
Crapo RO & Morris AH (1981a). Standardized single-breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 123, 185–189.[Medline]
Crapo RO, Morris AH & Gardner RM (1981b). Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 123, 659–664.[Medline]
Cremona G, Asnaghi R, Baderna P, Brunetto A, Brutsaert T, Cavallaro C, Clark TM, Cogo A, Donis R, Lanfranchi P, Luks A, Novello N, Panzetta S, Perini L, Putnam M, Spagnolatti L, Wagner H & Wagner PD (2002). Pulmonary extravascular fluid accumulation in recreational climbers: a prospective study. Lancet 359, 303–309.[CrossRef][Medline]
Dempsey J, Hanson P & Henderson K (1984). Exercise-induced arterial hypoxemia in healthy human subjects at sea level. J Physiol 355, 161–175.
Dempsey JA & Wagner PD (1999). Exercise-induced arterial hypoxemia. J Appl Physiol 87, 1997–2006.
Evans JW & Wagner PD (1977). Limits on VA/Q distributions from analysis of experimental inert gas elimination. J Appl Physiol 42, 889–898.
Gale G, Torre-Bueno J, Moon R, Saltzman H & Wagner P (1985). Ventilation-perfusion inequality in normal humans during exercise at sea-level and simulated altitude. J Appl Physiol 58, 978–988.
Gledhill N, Froese AB, Buick FJ & Bryan AC (1978). VA/Q inhomogeneity and AaDO2 in man during exercise: effect of SF6 breathing. J Appl Physiol 45, 512–515.
Gore CJ, Little SC, Hahn AG, Scroop GC, Norton KI, Bourdon PC, Woolford SM, Buckley JD, Stanef T, Campbell DP, Watson DB & Emonson DL (1997). Reduced performance of male and female athletes at 580m altitude. Eur J Appl Physiol 75, 136–143.[CrossRef]
Hammond M, Gale G, Kapitan K, Ries A & Wagner PD (1986a). Pulmonary gas exchange in humans during exercise at sea level. J Appl Physiol 60, 1590–1598.
Hammond M, Gale G, Kapitan K, Ries A & Wagner PD (1986b). Pulmonary gas exchange in humans during normobaric hypoxic exercise. J Appl Physiol 61, 978–988.
Hammond M & Hempleman S (1987). Oxygen diffusing capacity estimates derived from measured VA distributions in man. Respir Physiol 69, 129–147.[Medline]
Harms C, McClaran S, Nickele G, Pegelow D, Nelson W & Dempsey J (1998). Exercise-induced arterial hypoxemia in healthy young women. J Physiol 507, 619–628.
Harms C, McClaran S, Nickele G, Pegelow D, Nelson W & Dempsey J (2000). Effect of exercise-induced arterial O2 desaturation on VO2max in women. Med Sci Sports Exer 32, 1101–1108.[Medline]
Hopkins SR, Barker RC, Brutsaert T, Gavin TP, Entin P, Olfert IM, Veisel S & Wagner PD (2000). Pulmonary gas exchange during exercise in women: effects of exercise type and work increment. J Appl Physiol 89, 721–730.
Hopkins SR, Gavin TP, Siafakas N, Haseler L, Olfert IM, Wagner H & Wagner PD (1998). Effects of prolonged heavy exercise on pulmonary gas exchange in athletes. J Appl Physiol 85, 1523–1532.
Hopkins S, McKenzie D, Schoene R, Glenny R & Robertson H (1994). Pulmonary gas exchange during exercise in athletes I. Ventilation-perfusion mismatch and diffusion limitation. J Appl Physiol 77, 912–917.
McClaran S, Harms C, Pegelow D & Dempsey J (1998). Smaller lungs in women affect exercise hyperpnea. J Appl Physiol 84, 1872–1881.
Mead J (1980). Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity. Am Rev Respir Dis 121, 339–342.[Medline]
Piiper J & Scheid P (1980). Blood-gas equilibration in lungs. In Pulmonary Gas Exchange, ed. West JB, pp. 132–173. Academic Press, New York.
Prior BM, Modlesky CM, Evans EM, Sloniger MA, Saunders MJ, Lewis RD & Cureton KJ (2001). Muscularity and the density of the fat-free mass in athletes. J Appl Physiol 90, 1523–1531.
Rice AJ, Thornton AT, Gore CJ, Scroop GC, Greville HW, Wagner H, Wagner PD & Hopkins SR (1999). Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia. J Appl Physiol 87, 1802–1812.
Sansores R, Abboud R, Kennell C & Haynes N (1995). The effect of menstruation on the pulmonary carbon monoxide diffusing capacity. Am J Respir Crit Care Med 152, 381–384.[Abstract]
Thurlbeck WM (1982). Postnatal human lung growth. Thorax 37, 564–571.
Torre-Bueno J, Wagner P, Saltzman H, Gale G & Moon R (1985). Diffusion limitation in normal humans during exercise at sea level and simulated altitude. J Appl Physiol 58, 989–995.
Wagner P, Gale G, Moon R, Torre-Bueno J, Stolp B & Saltzman H (1986). Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 61, 260–270.
Wagner P, Naumann P & Laravuso R (1974). Simultaneous measurement of eight foreign gases in blood by gas chromatography. J Appl Physiol 36, 600–605.
Wagner PD, Smith CM, Davies NJ, McEvoy RD & Gale GE (1985). Estimation of ventilation-perfusion inequality by inert gas elimination without arterial sampling. J Appl Physiol 59, 376–383.
Wall J, Maskrey M, Wood-Baker R & Stedman W (2002). Exercise-induced oxyhaemoglobin desaturation, ventilatory limitation and lung diffusing capacity in women during and after exercise. Eur J Appl Physiol 87, 145–152.[CrossRef][Medline]
|
Acknowledgements |
|---|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
