Neurovascular Coupling Remains Intact During Incremental Ascent to High Altitude (4240 m) in Acclimatized Healthy Volunteers

Neurovascular coupling (NVC) is the temporal link between neuronal metabolic activity and regional cerebral blood flow (CBF), supporting adequate delivery of nutrients. Exposure to high altitude (HA) imposes several stressors, including hypoxia and hypocapnia, which modulate cerebrovascular tone in an antagonistic fashion. Whether these contrasting stressors and subsequent adaptations affect NVC during incremental ascent to HA is unclear. The aim of this study was to assess whether incremental ascent to HA influences the NVC response. Given that CBF is sensitive to changes in arterial blood gasses, in particular PaCO2, we hypothesized that the vasoconstrictive effect of hypocapnia during ascent would decrease the NVC response. 10 healthy study participants (21.7 ± 1.3 years, 23.57 ± 2.00 kg/m2, mean ± SD) were recruited as part of a research expedition to HA in the Nepal Himalaya. Resting posterior cerebral artery velocity (PCAv), arterial blood gasses (PaO2, SaO2, PaCO2, [HCO3-], base excess and arterial blood pH) and NVC response of the PCA were measured at four pre-determined locations: Calgary/Kathmandu (1045/1400 m, control), Namche (3440 m), Deboche (3820 m) and Pheriche (4240 m). PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analyzed using a portable blood gas/electrolyte analyzer. NVC was determined in response to visual stimulation (VS; Strobe light; 6 Hz; 30 s on/off × 3 trials). The NVC response was averaged across three VS trials at each location. PaO2, SaO2, and PaCO2 were each significantly decreased at 3440, 3820, and 4240 m. No significant differences were found for pH at HA (P > 0.05) due to significant reductions in [HCO3-] (P < 0.043). As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, whereas normal arterial pH was maintained due to renal compensation. NVC was quantified as the delta (Δ) PCAv from baseline for mean PCAv, peak PCAv and total area under the curve (ΔPCAv tAUC) during VS. No significant differences were found for Δmean, Δpeak or ΔPCAv tAUC between locations (P > 0.05). NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be preserved coincident with arterial pH maintenance during acclimatization

Renal Acid-Base Compensation Demonstrates Plasticity During Incremental Ascent to High Altitude

Ascent to high altitude, and the associated hypoxic ventilatory response, imposes an acid-base challenge, namely chronic hypocapnia and respiratory alkalosis. The kidneys act to compensate for this respiratory alkalosis via bicarbonate (HCO3-) excretion in urine to induce a compensatory metabolic acidosis. The time course and extent of plasticity of this important renal response during incremental ascent to altitude is unclear. We developed a practical index of renal reactivity (RR), indexing the relative change in arterial HCO3- concentration ([HCO3-]a; i.e., response) against the relative change in arterial partial pressure of CO2 (PaCO2; i.e., stimulus) during ascent (i.e., RR=Δ[HCO3-]a/ΔPaCO2). We sought to assess if RR increased over time and with incremental ascent to altitude, and if RR was correlated with relative changes in arterial pH (ΔpHa) throughout ascent. During ascent to 5160m over 10 days in the Nepal Himalaya, arterial blood was drawn from the radial artery for measurement of acid-base variables (Abbott iSTAT portable blood gas/electrolyte analyzer; CG4+ and CHEM8+ cartridges) in lowlanders at 1045/1400m (baseline) and at four different altitudes following one-night sleep: 3440m, 3820m, 4370m and 5160m. At 3820m (day five) and higher, RR significantly increased and plateaued in comparison to 3440m (day three; P<0.04), suggesting plasticity in renal acid-base compensation. At all four altitudes, we observed a strong correlation (range: r=-0.71 to -0.98; P<0.001) between RR and relative ΔpHa from baseline, suggesting that the RR index accurately quantified renal acid-base responsiveness throughout ascent. In conclusion, renal acid-base compensation mechanisms demonstrate plasticity during incremental ascent to high altitude, which was detected using a novel RR index. The extent of plasticity and plateau in renal responsiveness may predict severity of altitude illness or acclimatization at higher or more prolonged stays at altitude. Support or Funding Information: This work was supported by (a) Alberta Government Student Temporary Employment Program, (b) Alberta Innovates Health Solutions Summer Studentship, and (c) Natural Sciences and Engineering Research Council of Canada Discovery grant. *Indicates presente