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

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.

Worsening of central sleep apnea at high altitude--a role for cerebrovascular function.

Although periodic breathing during sleep at high altitude occurs almost universally, the likely mechanisms and independent effects of altitude and acclimatization have not been clearly reported. Data from 2005 demonstrated a significant relationship between decline in cerebral blood flow (CBF) at sleep onset and subsequent severity of central sleep apnea that night. We suspected that CBF would decline during partial acclimatization. We hypothesized therefore that reductions in CBF and its reactivity would worsen periodic breathing during sleep following partial acclimatization. Repeated measures of awake ventilatory and CBF responsiveness, arterial blood gases during wakefulness. and overnight polysomnography at sea level, upon arrival (days 2-4), and following partial acclimatization (days 12-15) to 5,050 m were made on 12 subjects. The apnea-hypopnea index (AHI) increased from to 77 ± 49 on days 2-4 to 116 ± 21 on days 12-15 (P = 0.01). The AHI upon initial arrival was associated with marked elevations in CBF (+28%, 68 ± 11 to 87 ± 17 cm/s; P < 0.05) and its reactivity to changes in PaCO2 [>90%, 2.0 ± 0.6 to 3.8 ± 1.5 cm·s(-1)·mmHg(-1) hypercapnia and 1.9 ± 0.4 to 4.1 ± 0.9 cm·s(-1)·mmHg(-1) for hypocapnia (P < 0.05)]. Over 10 days, the increases resolved and AHI worsened. During sleep at high altitude large oscillations in mean CBF velocity (CBFv) occurred, which were 35% higher initially (peak CBFv = 96 cm/s vs. peak CBFv = 71 cm/s) than at days 12-15. Our novel findings suggest that elevations in CBF and its reactivity to CO(2) upon initial ascent to high altitude may provide a protective effect on the development of periodic breathing during sleep (likely via moderating changes in central Pco2).

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m.

Brain blood flow increases during the first week of living at high altitude. We do not understand completely what causes the increase or how the factors that regulate brain blood flow are affected by the high-altitude environment. Our results show that the balance of oxygen (O(2)) and carbon dioxide (CO(2)) pressures in arterial blood explains 40% of the change in brain blood flow upon arrival at high altitude (5050 m). We also show that blood vessels in the brain respond to increases and decreases in CO(2) differently at high altitude compared to sea level, and that this can affect breathing responses as well. These results help us to better understand the regulation of brain blood flow at high altitude and are also relevant to diseases that are accompanied by reductions in the pressure of oxygen in the blood.

Initial orthostatic hypotension at high altitude.

There are several reports on syncope occurring following standing at high altitude (HA), yet description of the detailed physiological responses to standing at HA are lacking. We examined the hypothesis that appropriate physiological adjustments to upright posture would be compromised at HA (5050 m). Ten healthy volunteers stood up rapidly from supine rest, for 3 min, at sea level and at 5050 m. Beat-to-beat mean arterial blood pressure (MAP, Finometer), middle cerebral artery blood velocity (MCAv, Transcranial Doppler), end-tidal PCO(2) and PO(2), and heart rate (ECG) were recorded continuously. After 14 days at HA, baseline MAP and MCAv were not different to sea level, although HR was elevated. Neither the magnitude of initial (<15 s) responses to standing, nor the time course of initial recovery differed at HA compared with sea level (p > 0.05). By 3 min of standing, MAP was restored to supine values both at sea level (-3 +/- 12 mmHg) and HA (4 +/- 10 mmHg), although there was more complete recovery of HR at sea level (+13 +/- 10 b.min(-1), p = 0.02 vs. + 23 +/- 10 b.min(-1), p = 0.01). Reduced MCAv at 3 min was comparable at sea level and altitude (both -16%). These data indicate that initial cardiovascular and cerebrovascular responses to standing are unaltered when partially acclimatized to HA.