The need for specificity in quantifying neurocirculatory vs. respiratory effects of eucapnic hypoxia and transient hyperoxia.

Hypersensitivity of the carotid chemoreceptor leading to sympathetic nervous system activation and ventilatory instability has been implicated in the pathogenesis and consequences of several common clinical conditions. A variety of treatment approaches aimed at lessening chemoreceptor-driven sympathetic overactivity are now under investigation; thus, the ability to quantify this outcome variable with specificity and precision is crucial. Accordingly, we measured ventilatory and neurocirculatory responses to chemoreflex inhibition elicited by transient hyperoxia and chemoreflex excitation produced by exposure to graded, steady-state eucapnic hypoxia in middle-aged men and women (n = 82) with continuous positive airway pressure-treated obstructive sleep apnoea. Progressive, eucapnic hypoxia produced robust and highly variable increases in ventilation (+83 ± 59%) and muscle sympathetic nerve activity (MSNA) burst frequency (+55 ± 31%), whereas transient hyperoxia caused marked reductions in these variables (-35 ± 14% and -42 ± 16%, respectively). Coefficients of variation for ventilatory and MSNA burst frequency responses, indicating test-retest reproducibility, were respectively 9% and 24% for hyperoxia and 35% and 28% for hypoxia. Based on statistical measures of rank correlation or even comparisons across quartiles of corresponding ventilatory and MSNA responses, we found that the magnitudes of ventilatory inhibition with hyperoxia or excitation with eucapnic hypoxia were not correlated with corresponding MSNA responses within individuals. We conclude that, in conscious, behaving humans, ventilatory sensitivities to progressive, steady-state, eucapnic hypoxia and transient hyperoxia do not predict MSNA responsiveness. Our findings also support the use of transient hyperoxia as a reliable, sensitive, measure of the carotid chemoreceptor contribution to tonic sympathetic nervous system activity and respiratory drive.