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- Brutsaert, T. D., et al.
(author)
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Larger spleens and greater splenic contraction during exercise may be an adaptive characteristic of Nepali Sherpa at high-altitude
- 2024
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In: American Journal of Human Biology. - : Wiley. - 1042-0533 .- 1520-6300.
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Journal article (peer-reviewed)abstract
- Objectives: The 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]). Methods: To 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). Results: Resting 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), SpO2 decreased (~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 CaO2 with exercise (p-values from.026 to.037 and R2 values from 0.059 to 0.067 for the predictor variable). Conclusions: Larger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2 during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear.
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- Holmström, Pontus K., et al.
(author)
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Differential splenic responses to hyperoxic breathing at high altitude in Sherpa and lowlanders
- 2024
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In: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 109:4, s. 535-548
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Journal article (peer-reviewed)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; (Formula presented.) = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation ((Formula presented.)). 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].
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| 4. |
- Holmström, Pontus, et al.
(author)
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The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnea
- 2021
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In: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 106:1, s. 160-174
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Journal article (peer-reviewed)abstract
- Voluntary apnea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in hemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation (SpO2 ), which may cause tonic splenic contraction, which may contribute to hematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, SpO2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0), to 3440 m (day 3), 4240 m (day 7), and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnea-induced responses in HR, SpO2 and splenic volume were measured before and after two separate voluntary maximal apneas (A1-A2) at 1400 m, 3440 m and 4240 m. Resting spleen volume decreased -14.3% (-15.2 mL)/1000 m with ascent, from 140±41 mL (1400 m), to 108±28 mL (3440 m; P > 0.99), 94±22 mL (4240 m; P = 0.009) and 84±28 mL (5160 m; P = 0.029), with concomitant increases in [Hb] from 125±18.3 g/L (1400 m) to 128±10.4 g/L (3440 m), 138.8±12.7 g/L (4240 m) and 157.5±8 g/L (5160 m; P = 0.021). Apnea-induced splenic contraction was 50±15 mL (1400 m), 44±17 mL (3440 m; P > 0.99) and 26±8 mL (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnea-induced bradycardia was more pronounced at 3440 m (A1:P = 0.04; A2:P = 0.094) and at 4240 m (A1:P = 0.037 A2:P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to hematological acclimatization early in HA ascent in humans.
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- Schlebusch, Carina M., et al.
(author)
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Possible positive selection for an arsenic-protective haplotype in humans
- 2013
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:1, s. 53-58
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Journal article (peer-reviewed)abstract
- Background: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite.Objectives: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. Methods: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic.Results: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide microsatellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation FST = 0.006) and low levels of structure between SAC and HGDP populations (FST < 0.055 for all pairs of populations compared). Conclusions: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis.
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