Effects of nocturnal periodic breathing on sympathetic nerve activity and ventilatory control at high altitude: a randomised, crossover study

Abstract: During acute exposure to the hypoxia of high altitude, activation of the peripheral chemoreflex increases sympathetic nerve activity (SNA) and pulmonary ventilation. If exposure extends over several days, SNA and ventilation further increase and we investigated whether nocturnal periodic breathing (nPB) – a form of sleep-disordered breathing that is common at high altitude – contributes to these further increases. In a randomised, placebo-controlled, crossover protocol, twelve healthy men completed two 3-day sojourns in hypobaric hypoxia equivalent to 4000 m altitude. nPB was inhibited by increasing inspiratory CO2 fraction during the nights of one (nPB−), but not the other sojourn (nPB+). Ventilation and plasma catecholamines were measured daily, while muscle SNA (MSNA) was assessed before and at the end of sojourns, without and with peripheral chemoreflex inhibition (transient hyperoxia). The hypoxia-induced increases in MSNA burst frequency (nPB−, +104%; nPB+, +94%; P = 0.789) and incidence (nPB−, +47%; nPB+, +50%; P = 0.791) were not different between sojourns. Catecholamine concentrations throughout the sojourns were also similar (sojourn: P ≥ 0.271, time × sojourn: P ≥ 0.495). Ventilatory variables were not different between sojourns (sojourn: all P ≥ 0.090, time×sojourn: all P ≥ 0.062) except for a slightly greater tidal volume throughout nPB+ (sojourn: P = 0.047, time × sojourn: PP = 0.482). Chemoreflex inhibition induced similar reductions in ventilation during both sojourns (all P ≥ 0.151) and larger reductions in MSNA burst frequency (nPB−: −7.3 ± 2.7 bursts min−1, nPB+: −4.4 ± 5.1 bursts min−1, P = 0.037) and incidence after the nPB− (−0.9 ± 5.7 bursts (100 heart beats (HB))−1) than after the nPB+ sojourn (+2.4 ± 7.3 bursts (100 HB)−1, P = 0.046). We thus conclude that nPB does not contribute to the sympathoexcitation and hyperventilation associated with 3 days of exposure to high altitude. (Figure presented.). Key points: Prolonged exposure to high altitude leads to progressive increases in sympathetic nerve activity and pulmonary ventilation. Nocturnal periodic breathing (nPB), a form of sleep-disordered breathing that is common at high altitude, may contribute to these progressive increases in sympathetic nerve activity and ventilation. In this randomised, placebo-controlled, crossover study, twelve healthy men completed two 3-day sojourns in hypobaric hypoxia where nPB was either inhibited or not. The hypoxia-induced increases in sympathetic nerve activity and ventilation were not different between the two sojourns. We conclude that nPB does not contribute to the sympathoexcitation and hyperventilation associated with 3 days of exposure to high altitude.