Differential splenic responses to hyperoxic breathing at high altitude in Sherpa and lowlanders.

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; PO2${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation (SpO2${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$). 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]. What is the central question of this study?Indigenous Sherpa exhibit greater spleen size and enhanced exercise‐induced contraction at high altitude compared to lowlanders: how does spleen size of Sherpa and lowlanders respond to hyperoxic breathing at high altitude?What is the main finding and its importance?Sherpa do not experience any changes in spleen size when subjected to hyperoxic breathing at high altitude, whereas lowlanders show a 20% increase in spleen size under similar conditions. This may represent adaptive traits in Sherpa, potentially enhancing the spleen's capacity for contractions during increased metabolic demands. [ABSTRACT FROM AUTHOR]