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

Abstract

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.

Cardiorespiratory hysteresis during incremental high‐altitude ascent–descent quantifies the magnitude of ventilatory acclimatization

“…The reductions observed in both end‐tidal CO 2 and are similar to those observed previously with identical ascent profiles (e.g. Bruce et al., 2018; Leacy et al., 2018; Zouboules et al., 2018). The changes observed in the cardiorespiratory system during exposure to high altitude are a result of the HVR, in part.…”

“…Second, the acid-base status of our participants was not recorded during ascent and descent. However, in a previous study by our group incorporating an identical ascent profile we showed that arterial pH is remarkably stable during incremental ascent up to 5160 m (Leacy et al, 2018;Zouboules et al, 2018) Lastly, the time course of ascent and descent profiles was not uniform. Ascent from 1400 to 5160 m was achieved over 11 days.…”

“…Second, the acid–base status of our participants was not recorded during ascent and descent. However, in a previous study by our group incorporating an identical ascent profile we showed that arterial pH is remarkably stable during incremental ascent up to 5160 m (Leacy et al., 2018; Zouboules et al., 2018), suggesting adequate renal compensation during an 11 day incremental ascent model to 5160 m. In addition, previous work using the same ascent profile suggests that the portable capnograph we utilized here to assess PETCO2 underestimates PaCO2 at altitude (see Zouboules et al, 2018, Table 1). Thus, the absolute PETCO2 measures reported here should be interpreted with caution.…”

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea

“…During the first few days of exposure to HA, resting HR and vascular tone increase as a consequence of acute hypobaric hypoxia by stimulation of peripheral chemoreceptors, increasing sympathetic nervous system activity (Bärtsch & Gibbs, 2007;Hainsworth, Drinkhill, & Rivera-Chira, 2007). However, in the present investigation, resting HR and MAP were unchanged with ascent, most likely a response due to a relatively slow ascent profile with regular rest days enabling proper acclimatization to occur, as well as the vasodilatory effects of systemic hypoxia (Lafave et al, 2019;Leacy et al, 2018).…”

Is alkalosis the dominant factor in hypoxia‐induced cognitive dysfunction?

“…Indeed, hyperventilation‐induced hypocapnia was previously shown to suppress the neurovascular coupling response in healthy humans (Szabo et al., ). During hypocapnia, it is unclear whether the decreased partial pressure of carbon dioxide or the resultant alkalosis serves as the primary stimulus, but interestingly, neurovascular coupling was found to be intact in acclimatized healthy participants at high altitude, in whom profound hypocapnia was compensated over the course of several days by renal clearance of bicarbonate, restoring near‐normal pH (Leacy et al., ). Renal compensation would not have occurred in the study by Friend et al.…”