Pulmonary gas exchange in humans during exercise at sea level

Previous studies have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during exercise at simulated altitude and suggested that similar changes could occur even at sea level. We used the multiple-inert gas-elimination technique to further study gas exchange during exercise in healthy subjects at sea level. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate, minute ventilation, respiratory rate, and blood temperature were recorded at rest and during steady-state exercise in the following order: rest, minimal exercise (75 W), heavy exercise (300 W), heavy exercise breathing 100% O2, repeat rest, moderate exercise (225 W), and light exercise (150 W). Alveolar-to-arterial O2 tension difference increased linearly with O2 uptake (VO2) (6.1 Torr X min-1 X 1(-1) VO2). This could be fully explained by measured VA/Q inequality at mean VO2 less than 2.5 l X min-1. At higher VO2, the increase in alveolar-to-arterial O2 tension difference could not be explained by VA/Q inequality alone, suggesting the development of diffusion limitation. VA/Q inequality increased significantly during exercise (mean log SD of perfusion increased from 0.28 +/- 0.13 at rest to 0.58 +/- 0.30 at VO2 = 4.0 l X min-1, P less than 0.01). This increase was not reversed by 100% O2 breathing and appeared to persist at least transiently following exercise. These results confirm and extend the earlier suggestions (8, 21) of increasing VA/Q inequality and O2 diffusion limitation during heavy exercise at sea level in normal subjects and demonstrate that these changes are independent of the order of performance of exercise.     

Pulmonary gas exchange in humans exercising at sea level and simulated altitude

In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady-state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study.     

Alveolar PCO2 oscillations and ventilation at sea level and at high altitude.

This study examines the potential for a ventilatory drive, independent of mean PCO2, but depending instead on changes in PCO2 that occur during the respiratory cycle. This responsiveness is referred to here as "dynamic ventilatory sensitivity." The normal, spontaneous, respiratory oscillations in alveolar PCO2 have been modified with inspiratory pulses approximating alveolar PCO2 concentrations, both at sea level and at high altitude (5,000 m, 16,400 ft.). All tests were conducted with subjects exercising on a cycle ergometer at 60 W. The pulses last about half the inspiratory duration and are timed to arrive in the alveoli during early or late inspiration. Differences in ventilation, which then occur in the face of similar end-tidal PCO2 values, are taken to result from dynamic ventilatory sensitivity. Highly significant ventilatory responses (early pulse response greater than late) occurred in hypoxia and normoxia at sea level and after more than 4 days at 5,000 m. The response at high altitude was eliminated by normalizing PO2 and was reduced or eliminated with acetazolamide. No response was present soon after arrival (<4 days) at base camp, 5,000 m, on either of two high-altitude expeditions (BMEME, 1994, and Kanchenjunga, 1998). The largest responses at 5,000 m were obtained in subjects returning from very high altitude (7,100-8,848 m). The present study confirms and extends previous investigations that suggest that alveolar PCO2 oscillations provide a feedback signal for respiratory control, independent of changes in mean PCO2, suggesting that natural PCO2 oscillations drive breathing in exercise.