Abstract
Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO(2) will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO(2) will be reflected in an augmented ventilatory sensitivity to CO(2). We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation ((V) over dot(E)) at rest and during steady-state hyperoxic hypercapnia (7% CO(2)) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2-4, 7-9 and 12-15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 +/- 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7-9 days. Elevations in MCAv were strongly correlated (R(2) = 0.40) with the change in P(aO2)/P(aCO2) ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2-4 (P < 0.05 vs. sea level, 4.01 +/- 2.98 vs. 2.09 +/- 1.32 l min(-1) mmHg(-1)). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (similar to 40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO(2) may also affect ventilatory sensitivity.