Influence of cerebral blood flow on central sleep apnea at high altitude

Abstract

Study objectives: To further our understanding of central sleep apnea (CSA) at high altitude during acclimatization, we tested the hypothesis that pharmacologically altering cerebral blood flow (CBF) would alter the severity of CSA at high altitude.

Design: The study was a randomized, placebo-controlled single-blind study.

Setting: A field study at 5,050 m in Nepal.

Patients or participants: We studied 12 normal volunteers.

Interventions: Between days 5 to 10 at high altitude, CBF velocity (CBFv) was increased by intravenous (IV) acetazolamide (10 mg/kg) and reduced by oral indomethacin (100 mg).

Measurements and results: Arterial blood gases, hypoxic and hypercapnic ventilatory responses, and CBFv and its reactivity to carbon dioxide were measured awake. Overnight polysomnography was performed. The central apnea-hypopnea index was elevated following administration of indomethacin (89.2 ± 43.7 to 112.5 ± 32.9 events/h; mean ± standard deviation; P < 0.05) and was reduced following IV acetazolamide (89.2 ± 43.7 to 47.1 ± 48.1 events/h; P < 0.001). Intravenous acetazolamide elevated CBFv at high altitude by 28% (95% confidence interval [CI]: 22-34%) but did not affect ventilatory responses. The elevation in CBFv was partly mediated via a selective rise in partial pressure of arterial carbon dioxide (PaCO2) (28 ± 4 to 31 ± 3 mm Hg) and an associated fall in pH (P < 0.01). Oral indomethacin reduced CBFv by 23% (95% CI: 16-30%), blunted CBFv reactivity, and increased the hypercapnic ventilatory response by 66% (95% CI: 30-102%) but had no effect on PaCO2 or pH.

Conclusion: Our findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.

Keywords: central sleep apnea; cerebral blood flow; cerebral vascular reactivity; high altitude; ventilatory responses.

Figure 1

Overview of experimental design. NZ, New Zealand; IV, intravenous; ABG, arterial blood gas measurement; CBF, cerebral blood flow measurement; VRs, ventilatory response testing to hypoxia and hypercapnia; INDO, indomethacin; ACZ, acetazolamide.

Figure 2

Central sleep apnea versus time and drug administration. Mean ± SE bars.

Figure 3

The relationship between cerebral blood flow velocity (CBFv) and apnea-hypopnea index (AHI) after indomethacin administration. Delta MCAv D2 = change in cerebral blood flow velocity after Indomethacin (cm/sec). Delta AHI D2 = change in apnea-hypopnea index after Indomethacin (events/hour of sleep)