Time course and magnitude of ventilatory and renal acid-base acclimatization following rapid ascent to and residence at 3,800 m over nine days.

Rapid ascent to high altitude imposes an acute hypoxic and acid-base challenge, with ventilatory and renal acclimatization countering these perturbations. Specifically, ventilatory acclimatization improves oxygenation, but with concomitant hypocapnia and respiratory alkalosis. A compensatory, renally mediated relative metabolic acidosis follows via bicarbonate elimination, normalizing arterial pH(a). The time course and magnitude of these integrated acclimatization processes are highly variable between individuals. Using a previously developed metric of renal reactivity (RR), indexing the change in arterial bicarbonate concentration (Δ[HCO3-]a; renal response) over the change in arterial pressure of CO2 (Δ[Formula: see text]; renal stimulus), we aimed to characterize changes in RR magnitude following rapid ascent and residence at altitude. Resident lowlanders (n = 16) were tested at 1,045 m (day [D]0) prior to ascent, on D2 within 24 h of arrival, and D9 during residence at 3,800 m. Radial artery blood draws were obtained to measure acid-base variables: [Formula: see text], [HCO3-]a, and pHa. Compared with D0, [Formula: see text] and [HCO3-]a were lower on D2 (P < 0.01) and D9 (P < 0.01), whereas significant changes in pHa (P = 0.072) and RR (P = 0.056) were not detected. As pHa appeared fully compensated on D2 and RR did not increase significantly from D2 to D9, these data demonstrate renal acid-base compensation within 24 h at moderate steady-state altitude. Moreover, RR was strongly and inversely correlated with ΔpHa on D2 and D9 (r≤ -0.95; P < 0.0001), suggesting that a high-gain renal response better protects pHa. Our study highlights the differential time course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization following rapid ascent and residence at high altitude.NEW & NOTEWORTHY We assessed the time course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization with rapid ascent and residence at 3,800 m. Despite reductions in [Formula: see text] upon ascent, pHa was normalized within 24 h of arrival at 3,800 m through renal compensation (i.e., bicarbonate elimination). Renal reactivity (RR) was unchanged between days 2 and 9, suggesting a lack of plasticity at moderate steady-state altitude. RR was strongly correlated with ΔpHa, suggesting that a high-gain renal response better protects pHa.

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.

Spleen reactivity during incremental ascent to altitude.

The spleen contains a reservoir of red blood cells that are mobilized into circulation when under physiological stress. Despite the spleen having an established role in compensation to acute hypoxia, no previous work has assessed the role of the spleen during ascent to high altitude. Twelve participants completed 2 min of handgrip exercise at 30% of maximal voluntary contraction at 1,045, 3,440, and 4,240 m. In a subset of eight participants, an infusion of phenylephrine hydrochloride was administered at a dosage of 30 µg/l of predicted blood volume at each altitude. The spleen was imaged by ultrasound via a 2- to 5.5-MHz curvilinear probe. Spleen volume was calculated by the prolate ellipsoid formula. Finger capillary blood samples were taken to measure hematocrit. Spleen images and hematocrit were taken both before and at the end of both handgrip and phenylephrine infusion. No changes in resting spleen volume were observed between altitudes. At low altitude, the spleen contracted in response to handgrip [272.8 ml (SD 102.3) vs. 249.6 ml (SD 105.7), P = 0.009], leading to an increase in hematocrit (42.6% (SD 3.3) vs. 44.3% (SD 3.3), P = 0.023] but did not contract or increase hematocrit at the high-altitude locations. Infusion of phenylephrine led to spleen contraction at all altitudes, but only lead to an increase in hematocrit at low altitude. These data reveal that the human spleen may not contribute to acclimatization to chronic hypoxia, contrary to its response to acute sympathoexcitation. These results are explained by alterations in spleen reactivity to increased sympathetic activation at altitude. NEW & NOTEWORTHY The present study demonstrated that, despite the known role of the human spleen in increasing oxygen delivery to tissues during acute hypoxia scenarios, the spleen does not mobilize red blood cells during ascent to high altitude. Furthermore, the spleen's response to acute stressors at altitude depends on the nature of the stressor; the spleen's sensitivity to neurotransmitter is maintained, while its reflex response to stress is dampened.