Influence of high altitude on cerebrovascular and ventilatory responsiveness to CO2

Abstract

An altered acid-base balance following ascent to high altitude has been well established. Such changes in pH buffering could potentially account for the observed increase in ventilatory CO(2) sensitivity at high altitude. Likewise, if [H(+)] is the main determinant of cerebrovascular tone, then an alteration in pH buffering may also enhance the cerebral blood flow (CBF) responsiveness to CO(2) (termed cerebrovascular CO(2) reactivity). However, the effect altered acid-base balance associated with high altitude ascent on cerebrovascular and ventilatory responsiveness to CO(2) remains unclear. We measured ventilation , middle cerebral artery velocity (MCAv; index of CBF) and arterial blood gases at sea level and following ascent to 5050 m in 17 healthy participants during modified hyperoxic rebreathing. At 5050 m, resting , MCAv and pH were higher (P < 0.01), while bicarbonate concentration and partial pressures of arterial O(2) and CO(2) were lower (P < 0.01) compared to sea level. Ascent to 5050 m also increased the hypercapnic MCAv CO(2) reactivity (2.9 +/- 1.1 vs. 4.8 +/- 1.4% mmHg(1); P < 0.01) and CO(2) sensitivity (3.6 +/- 2.3 vs. 5.1 +/- 1.7 l min(1) mmHg(1); P < 0.01). Likewise, the hypocapnic MCAv CO(2) reactivity was increased at 5050 m (4.2 +/- 1.0 vs. 2.0 +/- 0.6% mmHg(1); P < 0.01). The hypercapnic MCAv CO(2) reactivity correlated with resting pH at high altitude (R(2) = 0.4; P < 0.01) while the central chemoreflex threshold correlated with bicarbonate concentration (R(2) = 0.7; P < 0.01). These findings indicate that (1) ascent to high altitude increases the ventilatory CO(2) sensitivity and elevates the cerebrovascular responsiveness to hypercapnia and hypocapnia, and (2) alterations in cerebrovascular CO(2) reactivity and central chemoreflex may be partly attributed to an acid-base balance associated with high altitude ascent. Collectively, our findings provide new insights into the influence of high altitude on cerebrovascular function and highlight the potential role of alterations in acid-base balance in the regulation in CBF and ventilatory control.

Figure 1

Ventilation () and middle cerebral artery velocity (MCAv) vs. end-tidal() from a representative individual during the modified rebreathing method at sea level and following ascent to 5050 m This graph depicts the typical breath-by-breath and MCAv vs. during modified rebreathing. The horizontal lines during modified rebreathing were used to calculate basal . The slopes represent linear regression used to calculate the ventilatory CO₂ sensitivity and cerebrovascular CO₂ reactivity during modified rebreathing.

Figure 2

Alterations in ventilatory and cerebrovascular responsiveness to hypercapnia at sea level and following ascent to 5050 m A, individual slopes; B group data (means ±s.d.). , ventilation; MCAv, middle cerebral artery velocity; CVCi, cerebrovascular vascular conductance index. **Different from sea level (P < 0.01).

Figure 3

Alterations in hypocapnic cerebrovascular reactivity following ascent to 5050 m A, individual slopes; B, group data (mean ±s.d.). MCAv, middle cerebral artery velocity. Ascent to 5050 m enhanced the cerebrovascular responsiveness to hypocapnia (voluntary hyperventilatory). **Different from sea level (P < 0.01).

Figure 4

Correlations between cerebrovascular CO₂ reactivity and ventilatory control with arterial blood gas variables Each point represents an individual subject at sea level and 5050 m. There were selective correlations between the cerebrovascular CO₂ reactivity (MCAv CO₂ reactivity) and pH at 5050 m, while no significant correlations were observed between MCAv CO₂ reactivity with either bicarbonate concentration or partial pressure of arterial CO₂. Ventilatory recruitment threshold correlated with [HCO₃⁻] at sea level and pooled data and selectively correlated with ventilatory CO₂ sensitivity ( CO₂ sensitivity) at 5050 m. These findings indicate that the increase in MCAv CO₂ reactivity and reduction in ventilatory recruitment threshold following ascent to 5050 m are related to an altered acid–balance balance. **Significant correlation (P < 0.01).