Combined hypoxia and hypercapnia evokes long-lasting sympathetic activation in humans.

We studied ventilatory and neurocirculatory responses to combined hypoxia (arterial O2 saturation 80%) and hypercapnia (end-tidal CO2 + 5 Torr) in awake humans. This asphyxic stimulus produced a substantial increase in minute ventilation (6.9 +/- 0.4 to 20.0 +/- 1.5 l/min) that promptly subsided on return to room air breathing. During asphyxia, muscle sympathetic nerve activity (intraneural microelectrodes) increased to 220 +/- 28% of the room air baseline. Approximately two-thirds of this sympathetic activation persisted after return to room air breathing for the duration of our measurements (20 min in 8 subjects, 1 h in 2 subjects). In contrast, neither ventilation nor sympathetic outflow changed during time control experiments. A 20-min exposure to hyperoxic hypercapnia also caused a sustained increase in sympathetic activity, but, unlike the aftereffect of asphyxia, this effect was short lived and coincident with continued hyperpnea. In summary, relatively brief periods of asphyxic stimulation cause substantial increases in sympathetic vasomotor outflow that outlast the chemical stimuli. These findings provide a potential explanation for the chronically elevated sympathetic nervous system activity that accompanies sleep apnea syndrome.