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

¹William Harvey Research Institute, Barts & The London Queen Mary School of Medicine & Dentistry, Charterhouse Square, London; ²Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford; ³Department of Respiratory Medicine, Northwick Park Hospital, Harrow, United Kingdom; ⁴Faculty of Human Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands; ⁵Pulmonary and Critical Care Medicine, University of Washington, Seattle, Washington; and ⁶York Hospitals NHS Foundation Trust, York, United Kingdom

Submitted 9 February 2007 ; accepted in final form 21 October 2007

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.

normal humans; respiratory control; dynamic CO₂ stimulus; altitude; oxygen supplementation; acetazolamide; PCO₂; hypoxia