Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans

Abstract

Recurrent and intermittent nocturnal hypoxia is characteristic of several diseases including chronic obstructive pulmonary disease, congestive heart failure, obesity-hypoventilation syndrome, and obstructive sleep apnea. The contribution of hypoxia to cardiovascular morbidity and mortality in these disease states is unclear, however. To investigate the impact of recurrent nocturnal hypoxia on hemodynamics, sympathetic activity, and vascular tone we evaluated 10 normal volunteers before and after 14 nights of nocturnal sustained hypoxia (mean oxygen saturation 84.2%, 9 h/night). Over the exposure, subjects exhibited ventilatory acclimatization to hypoxia as evidenced by an increase in resting ventilation (arterial Pco(2) 41.8 +/- 1.5 vs. 37.5 +/- 1.3 mmHg, mean +/- SD; P < 0.05) and in the isocapnic hypoxic ventilatory response (slope 0.49 +/- 0.1 vs. 1.32 +/- 0.2 l/min per 1% fall in saturation; P < 0.05). Subjects exhibited a significant increase in mean arterial pressure (86.7 +/- 6.1 vs. 90.5 +/- 7.6 mmHg; P < 0.001), muscle sympathetic nerve activity (20.8 +/- 2.8 vs. 28.2 +/- 3.3 bursts/min; P < 0.01), and forearm vascular resistance (39.6 +/- 3.5 vs. 47.5 +/- 4.8 mmHg.ml(-1).100 g tissue.min; P < 0.05). Forearm blood flow during acute isocapnic hypoxia was increased after exposure but during selective brachial intra-arterial vascular infusion of the alpha-blocker phentolamine it was unchanged after exposure. Finally, there was a decrease in reactive hyperemia to 15 min of forearm ischemia after the hypoxic exposure. Recurrent nocturnal hypoxia thus increases sympathetic activity and alters peripheral vascular tone. These changes may contribute to the increased cardiovascular and cerebrovascular risk associated with clinical diseases that are associated with chronic recurrent hypoxia.

Fig. 1.

Time line of the experiment. Experiments started at 8 AM. Reactive hyperemia (RH) was performed before instrumentation [i.e., arterial line and muscle sympathetic nervous system activity (MSNA)]. After instrumentation 15 min of recovery was allowed, and then baseline recording, intra-arterial vascular phentolamine infusion in the experimental arm, and isocapnic hypoxia were performed.

Fig. 2.

Blood pressure changes after 2-wk exposure. Open symbols, before recurrent hypoxia; closed symbols, after 2 wk of recurrent hypoxia. Significant differences were found between measurement for systolic, mean, and diastolic blood pressure (ANOVA P < 0.001 for all). *Significant differences in postexposure compared with preexposure values in post hoc analysis by Bonferroni test. Although across testing conditions arterial blood pressure tended to increase during isocapnic hypoxia, this change did not reach statistical significance.

Fig. 3.

Control and experimental forearm blood flow (FBF) and the ratio of experimental to control flow before (○) and after (•) 2 wk of recurrent hypoxia. Significant changes occurred in all parameters by ANOVA analysis: P < 0.001, P < 0.01, and P < 0.001, respectively. No significant differences in postexposure compared with preexposure values were found. *Significant differences in values across testing conditions in post hoc analysis by Bonferroni test.

Fig. 4.

FBF across time during RH plotted as individual values. *P < 0.05 compared with preexposure value.

Fig. 5.

MSNA before (Pre) and after (Post) exposure for individual subjects (n = 7). hb, Heartbeat. *P < 0.01 compared with Pre value.

Fig. 6.

These 1-min records of 3 subjects were chosen as representative of the magnitude of increase in MSNA with exposure. MSNA analysis was performed on 5-min samples. Subject 1 went from 23.5 to 25.2 bursts/min, subject 4 went from 25.1 to 41.0 bursts/min, and subject 5 went from 9.0 to 13.9 bursts/min.

Fig. 7.

Changes in MSNA during isocapnic hypoxia before and after exposure. *P < 0.01 compared with Pre value.