Determinants of ventilation and pulmonary artery pressure during early acclimatization to hypoxia in humans.

Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxiawere related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8-h isocapnic exposure to hypoxia (end-tidal PO2=55 Torr) in a purpose-built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (GpO2 ) and hyperoxic hypercapnia, the latter divided into peripheral (GpCO2 ) and central (GcCO2 ) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For GpO2 , GpCO2 and GcCO2 , but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre-acclimatization value. Additionally, the change in GpO2 during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only GpCO2 predicted the subsequent rise in ventilation and change in GpO2 during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial GpCO2 is a modest predictor of ventilatory acclimatization

Selected contribution: chemoreflex responses to CO2 before and after an 8-h exposure to hypoxia in humans.

The ventilatory sensitivity to CO2, in hyperoxia, is increased after an 8-h exposure to hypoxia. The purpose of the present study was to determine whether this increase arises through an increase in peripheral or central chemosensitivity. Ten healthy volunteers each underwent 8-h exposures to 1) isocapnic hypoxia, with end-tidal PO2 (PET(O2)) = 55 Torr and end-tidal PCO2 (PET(CO2)) = eucapnia; 2) poikilocapnic hypoxia, with PET(O2) = 55 Torr and PET(CO2) = uncontrolled; and 3) air-breathing control. The ventilatory response to CO2 was measured before and after each exposure with the use of a multifrequency binary sequence with two levels of PET(CO2): 1.5 and 10 Torr above the normal resting value. PET(O2) was held at 250 Torr. The peripheral (Gp) and the central (Gc) sensitivities were calculated by fitting the ventilatory data to a two-compartment model. There were increases in combined Gp + Gc (26%, P < 0.05), Gp (33%, P < 0.01), and Gc (23%, P = not significant) after exposure to hypoxia. There were no significant differences between isocapnic and poikilocapnic hypoxia. We conclude that sustained hypoxia induces a significant increase in chemosensitivity to CO2 within the peripheral chemoreflex

Human ventilatory response to CO2 after 8 h of isocapnic or poikilocapnic hypoxia.

During ventilatory acclimatization to hypoxia (VAH), the relationship between ventilation (VE) and end-tidal PCO2 (PETCO2) changes. This study was designed to determine 1) whether these changes can be seen early in VAH and 2) if these changes are present, whether the responses differ between isocapnic and poikilocapnic exposures. Ten healthy volunteers were studied by using three 8-h exposures: 1) isocapnic hypoxia (IH), end-tidal PO2 (PETO2) = 55 Torr and PETCO2 held at the subject's normal prehypoxic value; 2) poikilocapnic hypoxia (PH), PETO2 = 55 Torr; and 3) control (C), air breathing. The VE-PETCO2 relationship was determined in hyperoxia (PETO2 = 200 Torr) before and after the exposures. We found a significant increase in the slopes of VE-PETCO2 relationship after both hypoxic exposures compared with control (IH vs. C, P < 0.01; PH vs. C, P < 0.001; analysis of covariance with pairwise comparisons). This increase was not significantly different between protocols IH and PH. No significant changes in the intercept were detected. We conclude that 8 h of hypoxia, whether isocapnic or poikilocapnic, increases the sensitivity of the hyperoxic chemoreflex response to CO2