Testing Ventilatory Acclimatization to High Altitude using the Hyperoxic Ventilatory Withdrawal Test

Abstract

Testing the transient hypoxic ventilatory response (HVR) is the most common method utilized for assessing ventilatory acclimatization in the setting of high altitude ascent, as the peripheral chemoreceptors become sensitized to hypoxia with chronic exposure. However, this test requires sophisticated equipment (e.g., gas tanks, feedback controllers) that lacks portability, and may lead to participant discomfort while already hypoxic while at altitude. The transient hyperoxic withdrawal (HVW) test is simple, portable and safe, using a small 100% O2 tank available on most expeditions, and may better assess ventilatory acclimatization when participants are chronically hypoxic in high altitude fieldwork studies. We hypothesized that the HVW would be larger following 7-days of ascent to 4240m while taking acetazolamide (Diamox; i.e., ventilatory stimulant) than an acute hypoxic control group at low altitude, thus having utility in detecting ventilatory acclimatization during ascent to high altitude. Using two separate recruitments, we tested two groups in two contexts. In Part A, we recruited 14 participants to assess the HVW in the context of acute, steady-state hypoxia (~30-min; FIO2 13.5-14%) in a laboratory context (1045m, PATM ~665 mmHg). In Part B, 12 participants were recruited from a large research expedition to high altitude in the Nepal Himalaya, following 7 days of incremental ascent to high altitude (4240m, PATM ~460 mmHg), while taking prophylactic Diamox (125 mg, BID). Participants were instrumented with a mouthpiece and bacteriological filter attached to a calibrated pneumotachometer (to measure inspired ventilation; VI; L/min) and a peripheral pulse oximeter to measure oxygen saturation (SpO2;%). First, while breathing roughly equivalent PIO2 of ~85 mmHg at baseline (BL), both groups were exposed a single tidal breath of 100% O2 from a 50L Douglas bag by switching a three-way valve from room air to hyperoxia. The HVW was quantified as the change (delta) in VI from BL to the smallest instantaneous breath within 20-sec of the hyperoxic stimulus indexed to the change in SpO2 from BL to the peak following the hyperoxic breath, wherever it occurred (i.e., ventilatory response/oxygen change). We found that the HVW values from acute hypoxic participants had a mean of 0.34±0.23 L/min/%, while those who underwent acclimatization to high altitude hypoxia had a significantly larger HVW of 0.53±0.24 L/min/% (P=0.03). Our results suggest that the transient HVW test is a feasible method to detect peripheral chemoreceptor sensitization and ventilatory acclimatization in the context of high altitude ascent.