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 (∆[HCO3-]a; renal response) over the change in arterial pressure of CO2 (∆PaCO2; 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-hours of arrival, and D9 during residence at 3,800 m. Radial artery blood draws were obtained to measure acid-base variables: PaCO2, [HCO3-]a and pHa. Compared to D0, PaCO2 and [HCO3-]a were lower on D2 (P<0.01) and D9 (P<0.01), whereas significant changes in pHa (P>0.058) 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-hours at moderate steady-state altitude. Moreover, RR was strongly and inversely correlated with ∆pHa 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.

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.

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The aim of this study was to assess lipid peroxidation in chronic leg ischaemia by determining thiobarbituric acid reactants. Furthermore, Cu, Zn-superoxide dismutase and glutathione peroxidase activities as well as the trace element profile (Zn, Cu, Se, Mg) were determined. Fasting blood samples from the common femoral artery and vein were taken from both legs of 15 patients (57 ± 7 years) with peripheral arteriosclerosis and 9 individuals (54 ± 9 years) of the control group without chronic leg ischaemia.Patients with peripheral arteriosclerosis showed significantly decreased venous thiobarbituric acid reactant levels (2.01 ± 0.37 vs 2.39 ± 0.59 μπιοΐ/ΐ in controls, ρ < 0.05). Both arterial and venous samples from patients showed lower Cu, Zn-superoxide dismutase activities and higher glutathione peroxidase activities than controls. Venous activities of glutathione peroxidase were significantly higher than arterial activities in both groups (patients 0.52 ± 0.18 vs 0.43 ±0.15 μkat/g Hb, ρ < 0.001, control group 0.51 ± 0.12 vs 0.39 ±0.19 μkat/g Hb, ρ < 0.01). The trace element profile of the patients showed a highly significant decrease in magnesium levels (p < 0.001) and increased venous copper levels (p < 0.05). No significant changes were found in zinc and selenium levels. The results of this study show that during chronic leg ischaemia the production of free oxygen radicals at rest is well controlled, but the activity of antioxidant enzymes seems to be impaired.

High altitude exposure imposes a unique cerebrovascular challenge due to the presentation of two opposing blood gas stimuli. Specifically, hypoxia causes cerebral vasodilation, increasing cerebral blood flow (CBF), whereas respiratory‐induced hypocapnia causes cerebral vasoconstriction, decreasing CBF. Accordingly, arterial blood gases are large determinants of resting CBF, but the conflicting nature of these two superimposed chemostimuli presents a challenge in tracking CBF responsiveness with ascent to altitude. The extent that conflicting arterial blood gas variables affect CBF during incremental ascent to moderate altitude (i.e., the typical ascent profile for trekkers) is unclear. In 16 lowlanders during incremental ascent to altitude, we aimed to (a) characterize the relationship between arterial blood gas stimuli with regional and global CBF and (b) develop a novel index to track changes in CBF in relation to simultaneous but conflicting chemostmuli. During ascent to 4370m over seven days in the Nepal Himalaya, participants underwent serial resting measures at 1045m, 3440m (day 3) and 4370m (day 7) during incremental ascent to altitude. These measures included: arterial blood draws [radial artery; partial pressure of arterial (Pa)CO2, partial pressure of arterial (Pa)O2, arterial O2 saturation (SaO2)], unilateral anterior, unilateral posterior and global CBF (Duplex ultrasound; internal carotid artery [ICA] and vertebral artery [VA], global CBF [{ICA+VA}x2], respectively). We developed a novel stimulus index (SI), taking into account both chemostimuli (PaCO2/SaO2). Subsequently, both regional (ICA and VA) and global cerebral CBF were indexed against the SI to assess steady‐state cerebrovascular responsiveness (SS‐CVR). As expected, PaCO2, PaO2 and SaO2 all decreased with ascent to altitude (all P<0.001). SI remained relatively constant with ascent with a decrease observed at 4370m (P=0.07). Anterior (ICA) and global CBF did not increase significantly with ascent (P=0.15 and P=0.09, respectively), likely due to competing and simultaneous dilatory (hypoxia) and constricting (hypocapnia) chemostimuli. However, posterior (VA) CBF was significantly increased in comparison to baseline at 4370m (P=0.03). SS‐CVR for both regional and global CBF was significantly increased at 4370m (day 7 of altitude exposure; P<0.03) but not at 3440m (day 3 of altitude exposure; P0.08). Our data suggest that regional differences exist in CBF with incremental ascent, but that when indexed against superimposed and competing chemostimuli, SS‐CVR increases in both regional and global measures after seven days during incremental ascent to 4370m. Our novel SS‐CVR metric tracks cerebrovascular responsiveness during incremental ascent to moderate altitude, highlighting the importance of the braking effect of hypocapnia on cerebral blood flow regulation at altitude.Support or Funding InformationThis 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.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.