Difference in Steady‐state Chemoreflex Drive Between Groups With and Without a Patent Foramen Ovale

Abstract

Ventilatory acclimatization is a hallmark physiological response to high altitude. In ~30% of the population, a shunt located between the right and left atrium called patent foramen ovale (PFO) is present. People with a PFO have a reduced degree of ventilatory acclimatization which may contribute to their increased risk for high altitude illnesses. Recently, the development of a steady-state chemoreflex drive (SS-CD) index has provided a novel approach to assessing the overall ventilatory drive at altitude. Using data from a previous high-altitude expedition (AltitudeOmics), the SS-CD index (SS-CD = Minute ventilation (VE), / (arterial partial pressure of carbon dioxide (PaCO2) / arterial oxygen saturation (SaO2)) was utilized to quantify differences in the degree of ventilatory acclimatization between groups with a PFO, ­­­­­(PFO+) and without a PFO, (PFO-). We aimed to test two hypotheses: 1) PFO- subjects would have a higher SS-CD than PFO+ subjects 2) PFO+ subjects would have no significant change in their SS-CD from ALT1 to ALT16. Twenty-one participants (n=11 PFO+, n=10 PFO-) participated in a high-altitude study during which they spent 16 days at 5260 meters in Bolivia. VE, PaCO2, and SaO2 data were collected at sea level (SL), day 1 at 5260m (ALT1), and day 16 at 5260m (ALT16). VE was obtained using a pneumotach. PaCO2 and SaO2 were obtained from a radial artery catheter. A mixed-model 2 way repeat measure ANOVA was performed for statistical analysis with Tukey's multiple comparisons test. There was a main effect of time on the SS-CD (p<0.0001), but no significant difference between PFO+ and PFO- subjects (p=0.2). Within PFO+ and PFO- subject groups the SS-CD significantly increased from SL to ALT16 (PFO+ : 33.5 ± 5.9 vs 80.9 ± 47.8, p=0.0006; PFO- : 37.7 ± 10.3 vs 103.1 ± 44.2, p<0.0001) and from ALT1 and ALT16 (PFO+ : 43.16 ± 9.2 vs 80.9 ± 47.8, p=0.0077; PFO- : 52.08 ± 14.3 vs 103.1 ± 44.2, p=0.0052). Using the SS-CD to quantify chemoreceptor drive between groups, our findings suggest the overall chemoreflex drive from ALT1 to ALT16 in both groups reflects significant changes in ventilation. Additionally, PFO+ subjects exhibit no differences in their overall chemoreflex response to altitude from PFO- subjects, despite significant differences in a more classical index of drive (i.e., change in VE/change in SaO2). Future research should aim to investigate this inconsistency in chemoreflex responses in PFO+ and PFO- subjects at altitude.