Steady-state cerebral blood flow regulation at altitude: interaction between oxygen and carbon dioxide.

High-altitude ascent imposes a unique cerebrovascular challenge due to two opposing blood gas chemostimuli. Specifically, hypoxia causes cerebral vasodilation, whereas respiratory-induced hypocapnia causes vasoconstriction. The conflicting nature of these two superimposed chemostimuli presents a challenge in quantifying cerebrovascular reactivity (CVR) in chronic hypoxia. During incremental ascent to 4240 m over 7 days in the Nepal Himalaya, we aimed to (a) characterize the relationship between arterial blood gas stimuli and anterior, posterior and global (g)CBF, (b) develop a novel index to quantify cerebral blood flow (CBF) in relation to conflicting steady-state chemostimuli, and (c) assess these relationships with cerebral oxygenation (rSO2). On rest days during ascent, participants underwent supine resting measures at 1045 m (baseline), 3440 m (day 3) and 4240 m (day 7). These measures included pressure of arterial (Pa)CO2, PaO2, arterial O2 saturation (SaO2; arterial blood draws), unilateral anterior, posterior and gCBF (duplex ultrasound; internal carotid artery [ICA] and vertebral artery [VA], gCBF [{ICA + VA} × 2], respectively) and rSO2 (near-infrared spectroscopy). We developed a novel stimulus index (SI), taking into account both chemostimuli (PaCO2/SaO2). Subsequently, CBF was indexed against the SI to assess steady-state cerebrovascular responsiveness (SS-CVR). When both competing chemostimuli are taken into account, (a) SS-CVR was significantly higher in ICA, VA and gCBF at 4240 m compared to lower altitudes, (b) delta SS-CVR with ascent (1045 m vs. 4240 m) was higher in ICA vs. VA, suggesting regional differences in CBF regulation, and (c) ICA SS-CVR was strongly and positively correlated (r = 0.79) with rSO2 at 4240 m.

Renal reactivity: acid-base compensation during incremental ascent to high altitude.

KEY POINTS: Ascent to high altitude imposes an acid-base challenge in which renal compensation is integral for maintaining pH homeostasis, facilitating acclimatization and helping prevent mountain sicknesses. The time-course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear. We created a novel index that accurately quantifies renal acid-base compensation, which may have laboratory, fieldwork and clinical applications. Using this index, we found that renal compensation increased and plateaued after 5 days of incremental altitude exposure, suggesting plasticity in renal acid-base compensation mechanisms. The time-course and extent of plasticity in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude. ABSTRACT: Ascent to high altitude, and the associated hypoxic ventilatory response, imposes an acid-base challenge, namely chronic hypocapnia and respiratory alkalosis. The kidneys impart a relative compensatory metabolic acidosis through the elimination of bicarbonate (HCO3- ) in urine. The time-course and extent of plasticity of the renal response during incremental ascent is unclear. We developed an index of renal reactivity (RR), indexing the relative change in arterial bicarbonate concentration ([HCO3- ]a ) (i.e. renal response) against the relative change in arterial pressure of CO2 ( PaCO2 ) (i.e. renal stimulus) during incremental ascent to altitude ( Δ[HCO3-]a/ΔPaCO2 ). We aimed to assess whether: (i) RR magnitude was inversely correlated with relative changes in arterial pH (ΔpHa ) with ascent and (ii) RR increased over time and altitude exposure (i.e. plasticity). During ascent to 5160 m over 10 days in the Nepal Himalaya, arterial blood was drawn from the radial artery for measurement of blood gas/acid-base variables in lowlanders at 1045/1400 m and after 1 night of sleep at 3440 m (day 3), 3820 m (day 5), 4240 m (day 7) and 5160 m (day 10) during ascent. At 3820 m and higher, RR significantly increased and plateaued compared to 3440 m (P < 0.04), suggesting plasticity in renal acid-base compensations. At all altitudes, we observed a strong negative correlation (r ≤ -0.71; P < 0.001) between RR and ΔpHa from baseline. Renal compensation plateaued after 5 days of altitude exposure, despite subsequent exposure to higher altitudes. The time-course, extent of plasticity and plateau in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude.