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PERSPECTIVES |
John Rankin Laboratory of Pulmonary Medicine, Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI 53726, USA
Email: jdempsey{at}facstaff.wisc.edu
Historically, investigations in human physiology have been heavily biased toward the use of male rather than female subjects. For the study of pulmonary gas exchange during exercise a rather extensive descriptive database has been established for young healthy men. In brief, exercise of moderate to maximum intensity causes a progressive but variable widening of the alveolar to arterial PO2 difference (A–aDO2), attributable in part to a heterogeneous ventilation to perfusion (
A/
) distribution combined with a reduced mixed venous O2 content. Nevertheless, arterial PO2 (PaO2) is maintained close to resting values by a brisk hyperventilatory response to heavy intensity exercise. Exceptions are found in some highly trained endurance athletes who show significant reductions in PaO2 and arterial O2 saturation, secondary to an excessively widened A–aDO2 combined with a mechanical constraint on their hyperventilatory response.
In the current issue of The Journal of Physiology, Olfert et al. (2004) provide a comprehensive, carefully designed, unique comparison of exercise gas exchange in small groups of active, normally fit young men and women who were matched on the basis of age, height, lung volumes and O2 max. The multiple inert gas technique (MIGET), which is the best available method for quantifying functional A/ distribution throughout the lung, was applied across mild to near-maximum exercise intensities, in normoxia and hypoxia. Both groups of subjects widened their A-aDO2 slightly throughout exercise and mean A/ heterogeneity increased. However, sex differences in the A–aDO2, the fraction of the A–aDO2 accounted for by the measured A/ non-uniformity and the remaining portion of the A–aDO2 attributed by the authors to alveolar–capillary diffusion disequilibrium, were either not present or favoured a slightly more homogeneous A/ distribution in the women. Thus, these data show no major sex differences in the A–aDO2 or its major determinants during exercise – at least in these two groups of subjects.
There are several reasons to suspect that exercise gas exchange in healthy women may differ from that in men. Population studies have documented smaller vital capacities, FEV1.0 (forced expiratory volume at 1 s) and diffusion capacity (DLCO; diffusion capacity for CO) adjusted for age, sitting height and body mass in adult women. More limited data point to a reduced number of alveoli and reduced airway diameters relative to lung volume (i.e. dysanapsis) (Mead, 1980; Thurlbeck, 1982). Indeed, several investigations have reported sex differences during exercise, such as a lower DLCO and pulmonary capillary blood volume for women during exercise (Hsia et al. 1995), a mechanical constraint on exercise hyperpnoea at lower levels of ventilation and the appearance of an excessively widened A–aDO2 and arterial hypoxaemia in some highly active women, with O2 max considerably lower than that found in men who experience arterial oxygen desaturation during exercise. The findings of Olfert et al. (2004) suggest, then, that specific differences in lung volumes, body size, or O2 max may be responsible for these observations, rather than sex, per se. The accumulation of substantially more exercise data in healthy women who possess a wide range of O2 max is required to both extend the limited findings reported to date and to provide a sufficient basis for conducting multivariate correlational analyses.
The study of Olfert et al. (2004) also addresses broader questions of why exercise causes the A–aDO2 to widen and especially why this index of gas exchange efficiency should differ by as much as 2- to 3-fold during exercise among healthy subjects. The underlying causes of this variability in the A–aDO2 are likely to be precipitated by the high levels of pulmonary blood flow and O2 extraction demanded by heavy exercise. These requirements mean: (a) that even small individual differences in pulmonary capillary blood volume will critically alter red cell transit time and its distribution throughout the lung, thereby determining the completeness of diffusion equilibrium, and (b) that even smaller differences in any right to left shunt fractions will dictate whether arterial PO2 is maintained or reduced. The influence of A/ inequality is quantifiable within the limits of the MIGET technique, but during moderate to heavy exercise intensities one-half or more of the A–aDO2 is not accounted for by measured A/ distribution. As in the present study, this residual A–aDO2 is commonly attributed to diffusion disequilibrium, but in the face of exercise-induced reductions in mixed venous O2 content, extremely small shunts on the order of 1–3% of the cardiac output would also account for one-half or more of the observed A–aDO2 in normoxia. Post-pulmonary shunts in the coronary circulation do exist but their contribution remains unquantified in exercising humans. Potential intrapulmonary shunt pathways have been identified anatomically (Elliot & Reid, 1965; Tobin, 1966), but whether these shunts are open during exercise, and if so, to what extent remains untested. Significant amounts of prepulmonary capillary gas exchange have also been reported and are sensitive to the alveolar to capillary gas concentration gradients (Conhaim & Staub, 1980). Further investigations of the importance of this latter phenomenon is essential to our interpretation of measurements which use inert gases or hyperoxia in an attempt to quantify A/ distribution and shunt. Quantifying all of these potentially important influences on gas exchange in the exercising human will require innovative methods beyond the scope of those currently available.
In summary, Olfert et al. (2004) have provided a significant step forward by their careful, quantitative comparisons of men and women. Hopefully, these findings will provide an impetus for further, insightful investigations into the cardio-pulmonary physiology of exercise in the ‘forgotten’ sex.
References
Conhaim RL & Staub NC (1980). J Appl Physiol: Respir Environ Exercise Physiol 48, 848–856.
Elliot FM & Reid L (1965). Clin Radiol 16, 193–198.[CrossRef][Medline]
Hsia CCW, McBrayer DG & Ramanathan M (1995). Am J Respir Crit Care Med 152, 658–665.[Abstract]
Mead J (1980). Am Rev Respir Dis 121, 339–342.[Medline]
Olfert IM, Balouch J, Kleinsasser A, Knapp A, Wagner H, Wagner PD & Hopkins SR (2004). J Physiol 557, 519–531.
Thurlbeck WM (1982). Thorax 37, 564–571.[Abstract]
Tobin CE (1966). Thorax 21, 197–204.[Medline]
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