Keith R. Burgess, Andrew Dawson, Kelly Shepherd, Marianne Swart, Kate N. Thomas, Jui-Lin Fan, Rebekah A. I. Lucas, Samuel J. E. Lucas, James D. Cotter, Karen C. Peebles, Rishi Basnyat, Philip N. Ainslie. University of Sydney, Sydney, NSW, Australia. Peninsula Sleep Laboratory, NSW, Australia; University of Otago, Dunedin, New Zealand; Nepal International Clinic, Kathmandu, Nepal.

Exposure to high altitude causes a universal increase in central sleep apnea (CSA), mediated by alterations in ventilatory control and possibly in cerebral blood flow (CBF). The extent to which CSA changes over time at high altitude, and the extent to which it can be altered by pharmacologically induced alterations in CBF is unclear.

We hypothesised that partial acclimatisation and pharmacologically induced alteration of CBF would have separate effects on the frequency and duration of central apneas during sleep at high altitude. We studied 12 normal volunteers on four occasions over a three week period at 5050m, at Lobuje in northern Nepal. Measurements included overnight polysomnography with transcranial Doppler measurement of CBF, non invasive hemodynamics and ABG analysis at the Pyramid Research Station. They were studied at the beginning and end of their stay, to control for acclimatisation, and in between the control nights they were studied after pharmacological intervention. All subjects received oral Indomethacin 100mg and iv Acetazolamide (10mg/kg) 2 hours before sleep, in random order with placebo controls, at approximately 4 day intervals. The data from the pharmacological intervention nights were compared to the mean data from the control nights.

After Indomethacin, CBF fell by 22 ± 8% and the apneas lengthened from 13.9 ± 2.2 to 15.4 ± 3.3secs (p<0.01). Central Sleep Apnea Index (CSAI) increased from 96.4 ± 30.3 to 101 ± 28.2 apneas/hr (NS).

After Acetazolamide, CBF increased by 31 ± 6% , which had no effect on apnea duration but the CSAI fell from 96.4 ± 30.3 to 53.7 ± 45.7 apneas/hr (p<0.001).

During partial acclimatisation, CSAI increased from 76.9 ± 48.9 to 115.9 ± 20.2 /hr over the 12 day period (p=0.01), and apnea duration lengthened from 13.1 ± 2.6 to 14.6 ± 2.2 secs (p<0.02). Over the same period PaCO2 declined from 29±3 to 26±2mmHg, and the rise (25±10%) in CBF upon initial exposure (days 1-4) returned to its sea-level values. We propose that the increase in apnea length with Indomethacin was due to reductions in CBF and cerebrovascular reactivity and increase in “loop gain”. However the lengthening of the apneas due to acclimatisation must be due to mechanisms that are independent of CBF.

This study was supported by the Otago Medical Research Foundation, Peninsula Health Care p/l, Air Liquide p/l and the Italian National Research Council who kindly provided use of the EV-K2-CNR research laboratory.

Published On: September 15th, 2009 /