Author(s): MÖLLER, F., ELLIOTT, J.E., BOURDILLON, N., FAN, J.L., KAYSER, B., LAURIE, S.S., SUBUDHI, A.W., DAY, T.A., LOVERING, A.T., Institution: UNIVERSITY OF OREGON, Country: UNITED STATES, Abstract-ID: 1075

INTRODUCTION:
Ventilatory acclimatization is a form of respiratory plasticity that enables successful acclimatization to high altitude by progressively increasing chemoreceptor-driven ventilation at a given altitude to protect oxygenation. For unknown reasons, ventilatory acclimatization is impaired in individuals with a patent foramen ovale (PFO), which is an intracardiac shunt present in ~30% of the population (Lovering et al., 2022). Recently, the steady-state chemoreceptor drive (SSCD) has been proposed as an integrative index of prevailing respiratory drive, derived non-invasively as minute ventilation divided by a stimulus index (SI), defined as the ratio of end-tidal CO₂ to peripheral oxygen saturation (Johnson et al., 2025). In the present study, we used SSCD derived from direct arterial measures to quantify respiratory drive after 16 days of acclimatization to 5260m in participants with and without a PFO.
METHODS:
Resting measures were assessed in twenty participants with (PFO+; 11 (7 females) and without a PFO (PFO-: 9 (2 females) at sea level (SL) and at day 16 (ALT16) after rapid ascent to 5,260 m. The SSCD was derived from calculated alveolar ventilation (V̇A), arterial saturation (SaO₂), and partial pressure of arterial carbon dioxide (PaCO₂) derived from direct arterial blood gas and co-oximeter analyses. Two-way repeated-measures mixed-model ANOVAs with Tukey corrections for multiple comparisons were conducted for all variables on the factors time (SL, ALT16) and PFO (presence/absence).
RESULTS:
As a group, all variables demonstrated significant time effects (all p < 0.0001) with increased V̇A (+5 L min-1), reduced PaCO2 (-17 mmHg) and SaO2 (-16.7 mmHg) at ALT16, and a resulting increased SSCD (+29.5 a.u.). Pair-wise comparisons showed no group differences at SL, but there were significant main effects of PFO and PFO x Time for SSCD (p = 0.0227, p = 0.0111 respectively). However, PFO+ participants had a lower V̇A (-3.2 L min-1) and consequently a lower SaO2 (-4%) at ALT16, which resulted in a significantly lower SSCD (-23 a.u.) than PFO- participants.
CONCLUSION:
We found that the presence of a patent foramen ovale (PFO) was associated with a reduced SSCD, quantified directly from arterial blood draws. This reduced SSCD limited the expected improvement in SaO2 with acclimatization to high altitude after 16 days. The reason(s) SSCD was attenuated remains unknown, although it is possible that PFO+ participants require more time to effectively acclimatize to 5260m, potentially due to impairments in V̇/Q̇-matching and O2-exchange. Nevertheless, the relative attenuation in ventilatory drive after acclimatization in PFO+ may constrain expected improvements in exercise and cognitive performance at altitude. In applied settings, SSCD represents a promising metric for monitoring health and performance during high-altitude acclimatization.

Johnson (2025), Proc Natl Acad Sci, DOI: 10.1073/pnas.241256112
Lovering (2022), J Physiol, DOI: 10.1113/JP281108