Ventilatory and cerebrovascular responses to exercise in lowlander children acclimatizing to high-altitude

Maturational differences in chemoreception and cerebral blood flow are evident at sea-level, yet the age-related comparisons in cardiopulmonary and cerebrovascular responses to high-altitude exercise are unknown. Lowland living children (n = 8: 7-14 years) and adults (n = 10: 23-44 years) performed incremental cycle exercise to exhaustion at sea-level and following 6 days at 3800 m. Ventilation (V_E), end-tidal carbon dioxide ( $P_{\mathrm{ETC}{O}_2}$ ) and pulse oximetry estimation of oxygen saturation ( $S_{p{O}_2}$ ), as well as cerebrovascular measures of middle (MCA) and posterior (PCA) cerebral artery velocities (v) were measured at rest and throughout exercise. At high-altitude, both children and adults showed comparable increases in V_E and reductions in $P_{\mathrm{ETC}{O}_2}$ and $S_{p{O}_2}$ at rest (altitude: P < 0.001, group: P ≥ 0.22). During exercise, V_E increased at high-altitude compared to sea-level (P < 0.001), with no significant group differences (P = 0.134). Adults exhibited greater elevations in $P_{\mathrm{ETC}{O}_2}$ at sea-level compared to children (P = 0.023), but no significant group differences were present at high-altitude (P = 0.144). $S_{p{O}_2}$ reductions during high-altitude exercise were greater in adults than in children (80.4 ± 4.4% versus 85.8 ± 3.5%, P = 0.002), with both groups showing significant declines from sea-level (P < 0.001). No group differences in exercise induced changes in MCAv (P = 0.159) or PCAv (P = 0.674) were present at sea-level, but at high-altitude, children displayed greater MCAv (82.8 ± 9.7 versus 71.6 ± 7.8 cm s^-1, P = 0.014) and PCAv responses versus adults (61.8 ± 8.1 versus 46.7 ± 10.0 cm s^-1, P = 0.001). Exposure to high-altitude resulted in a greater cerebral blood velocity response during exercise in children, despite a greater preservation of oxygenation and a comparable degree of hypocapnia, suggesting differential thresholds of O₂ and CO₂ prioritization. KEY POINTS: Children and adults exhibit distinct ventilatory and cerebrovascular responses to exercise, which may influence their acclimatization to high-altitude environments. Children (ages 7-14 years) and adults (ages 23-44 years) were brought from sea-level to high-altitude (3800 m), where changes in cardiopulmonary and cerebrovascular responses were assessed during incremental exercise. At high-altitude, both groups showed comparable increases in ventilation and similar levels of hypocapnia. However, children showed a lower magnitude of peripheral oxygen desaturation during high-altitude exercise. Despite better preservation of oxygenation, children showed a greater increase in cerebral blood velocity during exercise, suggesting an increased prioritization of oxygen delivery to the brain. These results improve our understanding of the age-related differences in cerebrovascular sensitivity during exercise at sea-level and high-altitude, indicating a dominance of hypoxic vasodilatation and reduced sensitivity to endogenous carbon dioxide during exercise.