An official website of the United States government
Abstract The human spleen contracts in response to stress‐induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry. Our study included 14 non‐Sherpa (7 female) residing at altitude for a mean continuous duration of 3 months and 46 Sherpa (24 female) with an average of 4 years altitude exposure. Participants underwent a hyperoxic breathing test at altitude (4300 m; barrometric pressure = ∼430 torr; = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation (). During rest, Sherpa exhibited larger spleens (226 ± 70 mL) compared to non‐Sherpa (165 ± 34 mL;P < 0.001; effect size (ES) = 0.95, 95% CI: 0.3–1.6). In response to hyperoxia, non‐Sherpa demonstrated 22 ± 12% increase in spleen size (35 ± 17 mL, 95% CI: 20.7–48.9;P < 0.001; ES = 1.8, 95% CI: 0.93–2.66), while spleen size remained unchanged in Sherpa (−2 ± 13 mL, 95% CI: −2.4 to 7.3;P = 0.640; ES = 0.18, 95% CI: −0.10 to 0.47). Our findings suggest that Sherpa and non‐Sherpas of lowland ancestry exhibit distinct variations in spleen volume during hyperoxia at high altitude, potentially indicating two distinct splenic functions. In Sherpa, this phenomenon may signify a diminished splenic response to altitude‐related hypoxia at rest, potentially contributing to enhanced splenic contractions during physical stress. Conversely, non‐Sherpa experienced a transient increase in spleen size during hyperoxia, indicating an active tonic contraction, which may influence early altitude acclimatization in lowlanders by raising [Hb].
more »
« less
Larger spleens and greater splenic contraction during exercise may be an adaptive characteristic of Nepali Sherpa at high‐altitude
Abstract ObjectivesThe Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea‐induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress‐induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]). MethodsTo investigate splenic contraction in response to exercise at high‐altitude (4300 m; Pb = ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non‐Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with [Hb] and oxygen saturation (SpO2). ResultsResting spleen volume was larger in the Sherpa compared with Nepali non‐Sherpa (237 ± 62 vs. 165 ± 34 mL,p < .001), as was the exercise‐induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL,p < .001). From rest to exercise, [Hb] increased (1.2 to 1.4 g.dl−1), SpO2decreased (~9%) and calculated arterial oxygen content (CaO2) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in [Hb] and CaO2with exercise (p‐values from .026 to .037 and R2values from 0.059 to 0.067 for the predictor variable). ConclusionsLarger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear.
more »
« less
- Award ID(s):
- 2216548
- PAR ID:
- 10507094
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- American Journal of Human Biology
- ISSN:
- 1042-0533
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract BackgroundComplex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2consumption,V̇O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2transport pathway to examine the links between cardiorespiratory traits andV̇O2max. ResultsPhysiological experiments revealed that increases in Hb-O2affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement inV̇O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2affinity onV̇O2max in hypoxia was contingent on the capacity for O2diffusion in active tissues. ConclusionsThese results suggest that increases in Hb-O2affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2affinity is contingent on the capacity to extract O2from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.more » « less
-
RationaleCoordinatively driven self‐assembly of transition metal ions and bidentate ligands gives rise to organometallic complexes that usually contain superimposed isobars, isomers, and conformers. In this study, the double dispersion ability of ion mobility mass spectrometry (IM‐MS) was used to provide a comprehensive structural characterization of the self‐assembled supramolecular complexes by their mass and charge, revealed by the MS event, and their shape and collision cross‐section (Ω), revealed by the IM event. MethodsSelf‐assembled complexes were synthesized by reacting a bis(terpyridine) ligand exhibiting a 60odihedral angle between the two ligating terpyridine sites (T) with divalent Zn, Ni, Cd, or Fe. The products were isolated as (Metal2+[T])n(PF6)2nsalts and analyzed using IM‐MS after electrospray ionization (ESI) which produced several charge states from eachn‐mer, depending on the number of PF6ˉ anions lost upon ESI. Experimental Ω data, derived using IM‐MS, and computational Ω predictions were used to elucidate the size and architecture of the complexes. ResultsOnly macrocyclic dimers, trimers, and tetramers were observed with Cd2+, whereas Zn2+formed the same plus hexameric complexes. These two metals led to the simplest product distributions and no linear isomers. In sharp contrast, Ni2+and Fe2+formed all possible ring sizes from dimer to hexamer as well as various linear isomers. The experimental and theoretical Ω data indicated rather planar macrocyclic geometries for the dimers and trimers, twisted 3D architectures for the larger rings, and substantially larger sizes with spiral conformation for the linear congeners. Adding PF6ˉ to the same complex was found to mainly cause size contraction due to new stabilizing anion–cation interactions. ConclusionsComplete structural identification could be accomplished using ESI‐IM‐MS. Our results affirm that self‐assembly with Cd2+and Zn2+proceeds through reversible equilibria that generate the thermodynamically most stable structures, encompassing exclusively macrocyclic architectures that readily accommodate the 60oligand used. In contrast, complexation with Ni2+and Fe2+, which form stronger coordinative bonds, proceeds through kinetic control, leading to more complex mixtures and kinetically trapped less stable architectures, such as macrocyclic pentamers and linear isomers.more » « less
-
With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid–base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability. Differential renal compensation between acclimatizing lowlanders (LL) and Tibetan highlanders (TH; Sherpa) with ascent was previously unknown. We assessed ventilatory and renal acclimatization between unacclimatized LL and TH during incremental ascent from 1,400 m to 4,300 m in age- and sex-matched groups of 15-LL (8F) and 14-TH (7F) of confirmed Tibetan ancestry. We compared respiratory and renally mediated blood acid–base acclimatization (PCO2, [HCO3−], pH) in both groups before (1,400 m) and following day 8 to 9 of incremental ascent to 4,300 m. We found that following ascent to 4,300 m, LL had significantly lower PCO2(P<0.0001) and [HCO3−] (P<0.0001), and higher pH (P= 0.0037) than 1,400 m, suggesting respiratory alkalosis and only partial renal compensation. Conversely, TH had significantly lower PCO2(P< 0.0001) and [HCO3−] (P< 0.0001), but unchanged pH (P= 0.1), suggesting full renal compensation, with significantly lower PCO2(P= 0.01), [HCO3−] (P< 0.0001) and pH (P= 0.005) than LL at 4,300 m. This demonstration of differential integrative respiratory–renal responses between acclimatizing LL and TH may indicate selective pressure on TH, and highlights the important role of the kidneys in acclimatization.more » « less
-
Abstract The microstructural properties of deep arc cumulates (arclogites) are poorly understood, but are essential in gaining a comprehensive picture of the rheology of continental lithosphere. Here, we analyze 16 arclogite xenoliths, comprising a low MgO and a high MgO suite, from Arizona, USA using electron backscatter diffraction to map microstructures, clinopyroxene shape preferred orientations (SPO), and clinopyroxene crystallographic preferred orientations (CPO). The lower pressure (∼1 GPa) low MgO arclogites show a variety of different clinopyroxene fabrics (S, L, and LS‐type), whereas the high pressure (>2 GPa) high MgO arclogites show predominantly LS‐type fabrics. Furthermore, clinopyroxenes in low MgO arclogites all show a pronounced correspondence between the long axis of their grain shape ellipsoids with the [001] crystal direction, indicating an SPO control on the CPO. In contrast, high MgO arclogite clinopyroxenes lack such a correspondence. We propose that both arclogite types originated as igneous cumulates, consistent with previous studies, but that the high MgO suite experienced substantial recrystallization which diminished the original igneous SPO‐induced CPO. Using strain rates appropriate for arc settings, we calculate a strength profile for the lithosphere and argue that the deepest arclogite textures are consistent with lithospheric foundering through ductile deformation under high shear strain (10−14–10−12 s−1). Our study shows that there is a high degree of shear strain localization in deep arc roots while shallower portions are relatively undeformed.more » « less
