Effects of gas density on experimentally obstructed ventilation during acute hypoxia

When patients with obstructive lung disease breathe helium–oxygen mixtures, their arterial PCO2 is lowered towards normal, indicating more effective ventilation. However, there is a lack of detailed respiratory data from clinical cases, so that the mechanisms remain unclear. To study relevant variables during hypoxemia and obstruction in the absence of disease, we undertook experiments with healthy subjects breathing normoxic and hypoxic gas mixtures of differing densities (air, 13.7% O2 in N2 and 13.7% O2 in helium) through an experimental obstruction (resistive airway loading). This increased airway resistance was twice that reported from the ambient-pleural pressure differences in patients with moderately severe emphysema. Without imposed resistance the total ventilation (V̇e) increased 27% on both hypoxic mixtures. With normoxia, the obstruction increased tidal volume but decreased frequency so that V̇e and alveolar ventilation (V̇a) were essentially unchanged. With hypoxia, breathing pattern changed similarly, but now V̇e decreased while V̇a was maintained. Helium returned the breathing patterns toward normal. Obstruction lowered the rapid increase in V̇e from two or three breaths of N2, but the decrease from two or three breaths of O2 was unchanged. We detected an increase in metabolic rate with obstructed breathing that was reduced by the helium mixtures. The remarkable finding was that despite the obstruction being markedly uncomfortable because of the high resistance, we did not find any substantial disturbance in gas exchange, compared to hypoxia with no obstruction. Thus, the main mechanisms responsible for improved blood gases in patients breathing helium mixtures were outside the scope of our experiment and likely related to disease factors.