Steady-state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide

稳态化学反射驱动可捕捉逐步上升至高海拔过程中的通气适应:乙酰唑胺的作用

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Abstract

Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady-state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady-state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady-state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude-related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady-state measurements of resting ventilation (V̇(I) ; L/min), pressure of end-tidal (P(ET) )CO(2) (Torr), and peripheral oxygen saturation (SpO(2) ; %) were measured. A stimulus index (SI; P(ET) CO(2) /SpO(2) ) was calculated, and SSCD was calculated by indexing V̇(I) against SI. We found that (a) both V̇(I) and SSCD increased with ascent to 4240 m (day seven; V̇(I) : +39%, p < 0.0001, Hedges' g = 1.52; SSCD: +56.%, p < 0.0001, Hedges' g = 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇(I) : p = 0.02, Hedges' g = 1.04; SSCD: p = 0.02, Hedges' g = 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests.

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