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
Oxygen transport phenotypes and the adaptive modes of Andean versus Tibetan highland native populations
High altitude native populations exhibit physiological adaptations to environmental hypoxia. It has been hypothesized that two of these populations, Andeans and Tibetans, demonstrate distinct adaptive modes with the former characterized by increased blood oxygen content, and the latter characterized by increased blood flow. To investigate this hypothesis, we recruited two groups of healthy adults (ages 18-35) with highland ancestry who were born and currently reside at high altitude. The groups were: Andean Quechuas recruited in Cerro de Pasco, Peru (AND, n = 301) and Tibetan Sherpas recruited in Pheriche, Nepal (SHP, n = 64). Participants were tested in field laboratories using identical equipment and protocols, at nearly identical altitudes (4,330m and 4,371m, respectively). We assessed a wide variety of physiological variables at rest, submaximal exercise, and maximal exercise. We found that although some phenotypes aligned with the above hypothesis, the majority did not. For example, as predicted, AND displayed significantly lower (p<0.001) ventilatory equivalents for oxygen (VE/VO2) at rest. However, this trend reversed at maximal exercise, with AND displaying significantly higher (p<0.001) VE/VO2 than SHP. Further, contrary to the above hypothesis, we found no statistically significant differences in flow-mediated dilation between the groups. These results suggest that the adaptive modes of these populations are perhaps not as distinct as previously supposed. Given that this hypothesis was formulated on the basis of data taken at rest, our data highlights the importance of assessing physiology both at rest and exercise, to gain a more complete understanding of adaptation to high altitude.
more »
« less
- Award ID(s):
- 2141893
- PAR ID:
- 10465721
- Date Published:
- Journal Name:
- American journal of biological anthropology
- ISSN:
- 2692-7691
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Most animals elevate cardiac output during exercise through a rise in heart rate ( f H ), whereas stroke volume (V S ) remains relatively unchanged. Cardiac pacing reveals that elevating f H alone does not alter cardiac output, which is instead largely regulated by the peripheral vasculature. In terms of myocardial oxygen demand, an increase in f H is more costly than that which would incur if V S instead were to increase. We hypothesized that f H must increase because any substantial rise in V S would be constrained by the pericardium. To investigate this hypothesis, we explored the effects of pharmacologically induced bradycardia, with ivabradine treatment, on V S at rest and during exercise in the common snapping turtle ( Chelydra serpentina) with intact or opened pericardium. We first showed that, in isolated myocardial preparations, ivabradine exerted a pronounced positive inotropic effect on atrial tissue but only minor effects on ventricle. Ivabradine reduced f H in vivo, such that exercise tachycardia was attenuated. Pulmonary and systemic V S rose in response to ivabradine. The rise in pulmonary V S largely compensated for the bradycardia at rest, leaving total pulmonary flow unchanged by ivabradine, although ivabradine reduced pulmonary blood flow during swimming (exercise × ivabradine interaction, P < 0.05). Although systemic V S increased, systemic blood flow was reduced by ivabradine both at rest and during exercise, despite ivabradine’s potential to increase cardiac contractility. Opening the pericardium had no effect on f H , V S , or blood flows before or after ivabradine, indicating that the pericardium does not constrain VS in turtles, even during pharmacologically induced bradycardia.more » « less
-
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
-
Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.more » « less
-
BACKGROUND: Almost 95% of the venous valves are micron scale found in veins smaller than 300μm diameter. The fluid dynamics of blood flow and transport through these micro venous valves and their contribution to thrombosis is not yet well understood or characterized due to difficulty in making direct measurements in murine models. OBJECTIVE: The unique flow patterns that may arise in physiological and pathological non-actuating micro venous valves are predicted. METHODS: Computational fluid and transport simulations are used to model blood flow and oxygen gradients in a microfluidic vein. RESULTS: The model successfully recreates the typical non-Newtonian vortical flow within the valve cusps seen in preclinical experimental models and in clinic. The analysis further reveals variation in the vortex strengths due to temporal changes in blood flow. The cusp oxygen is typically low from the main lumen, and it is regulated by systemic venous flow. CONCLUSIONS: The analysis leads to a clinically-relevant hypothesis that micro venous valves may not create a hypoxic environment needed for endothelial inflammation, which is one of the main causes of thrombosis. However, incompetent micro venous valves are still locations for complex fluid dynamics of blood leading to low shear regions that may contribute to thrombosis through other pathways.more » « less