A Novel Measurement of Loop Gain Via Voluntary End-Expiratory Breath Holds During Acclimatization to High Altitude: Relationship to Central Sleep Apnea

Central sleep apnea (CSA) is universal at high altitude (HA; hypobaric hypoxia), with a high degree of variability. CSA increases in incidence and severity with ascent above 3,000m and with increased time spent at HA, due in part to increases in chemoreflex sensitivity (i.e., loop gain; LG) resulting from ventilatory acclimatization (VA). CSA is characterized by alternating reductions (hypopnea) or complete absence of airflow (apnea) during sleep, separated by intermittent periods of hyperventilation, and is thought to be associated with a LG ratios >1.0. In HA fieldwork expeditions, testing respiratory chemoreflex sensitivity using traditional lab-based steady-state methods may not be relevant to CSA, nor feasible to predict those susceptible to CSA with ascent to HA. While CSA is universal with ascent to HA, it remains unclear how the incidence and severity of CSA may be related to LG with early ascent, given the high between-individual variability. Before (1400m; Day 0) and during early acclimatization to HA (4300m; days 6-8) in 11 healthy participants, we aimed to characterize a novel breath-holding protocol to quantify LG and assess the relationship between LG and CSA severity. We hypothesized that (a) LG will be <1.0 before ascent, and subsequently will be >1.0 with early incremental ascent to 4300m, suggesting VA and susceptibility for CSA, and (b) there will be an increase in the incidence and severity of CSA with ascent to HA, which will be correlated with LG, within-individual. In both locations, we used a series of five ~10-sec voluntary end-expiratory breath holds (EEBHs) separated by a ~60-sec recovery period to quantify LG. Following the breath-hold protocol, we utilized portable sleep monitors to assess the incidence and severity of CSA via the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) during sleep. AHI and ODI increased significantly compared to 1400m (p<0.0001), indicating CSA. LG using the 1st breath following apnea (LG1) was significantly larger at 4300m (1.54±0.75 a.u.) than 1400m (0.89±0.73 a.u.; P=0.04, ES=0.88). Calculating LG using an average of the 1st and 2nd breaths following apnea (LG1+2) was also significantly larger at 4300m (1.09±0.51 a.u.) than 1400m (0.62±0.39 a.u.; P=0.022, ES=1.04). LG1 was strongly correlated with AHI (r=0.76, P=0.007) and moderately correlated with ODI (r=0.66, P=0.029). LG1+2 was strongly correlated with both AHI (r=0.78, P=0.004) and ODI (r=0.7, P=0.017). These data suggest that this EEBH protocol is well-suited to quantifying chemoreflex LG during VA to HA, and may have utility for predicting the incidence and severity of CSA in individuals in the context of HA fieldwork. MRU, NSERC, NSF. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.