Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS.

The fractional increase in cerebral blood flow (CBF) velocity (VCBF) from the control value with 5-min steps of isocapnic hypoxia and hyperoxic hypercapnia was measured by transcranial Doppler in six sea-level native men before and during a 5-day sojourn at 3,810 m altitude to determine whether cerebral vasoreactivity to low arterial O2 saturation (SaO2) gradually increased [as does the hypoxic ventilatory response (HVR)] or diminished (adapted, in concert with known slow fall of CBF) at altitude. A control resting PCO2 value was chosen each day during preliminary hyperoxia to set ventilation at 140 ml.kg-1.min-1 for this and the parallel HVR study, attempting to establish control cerebrospinal fluid (CSF) and brain extracellular fluid pH values unaltered by acclimatization. The relationship of CBF to SaO2 was nonlinear, steepening at a lower SaO2. A hyperbolic equation was used to describe hypoxic cerebrovascular reactivity: fractional VCBF = x[60/ (SaO2-40)-1], where X is the fractional increase of VCBF at 70%.X rose from 0.346 +/- 0.104 (SD) at sea level to 0.463 +/- 0.084 on altitude day 5 (P < 0.05 by paired t-test, justified by the a priori experimental plan). For comparison with CO2 sensitivity, from these X values, we estimate the rise in CBF in response to a 1% fall in SaO2 at 80% to be 1.30% at sea level and 1.74% after 5 days at altitude. CBF sensitivity to increased end-tidal PCO2 rose from 4.01 +/- 0.62%/Torr at sea level to 5.12 +/- 0.79%/Torr on day 5 (P < 0.05), as expected, at the lower PCO2 due to the logarithmic relationship of PCO2 to CSF pH. This change was not significant after correction to log PCO2. We conclude that the cerebral vascular response to acute isocapnic hypoxia may increase during acclimatization at high altitude. The mechanism is unknown but is presumably unrelated to the parallel carotid chemosensitization that, in these subjects, increased the HVR by 60% in the same 5-day period from 0.91 +/- 0.38 to 1.46 +/- 0.59 l.min-1.% fall in SaO2-1).

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One oral dose of 1,000 mg of acetazolamide caused an acute 38% increase in cerebral blood flow (CBF) in eight healthy volunteers. During the following 10 days the subjects took 1,000 mg acetazolamide daily. CBF normalized within the first 2 days. The drug induced mild hyperventilation, gradually decreasing alveolar PCO2 to 70% of the control value at the end of the treatment period. In healthy humans the hyperventilation will not increase brain oxygenation significantly at sea level. But at high altitudes the enhanced ventilatory drive will improve oxygenation of the brain, and this may account for the beneficial effects of the drug on the symptoms of acute mountain sickness. During the treatment there was a significant 10% decrease of the hematocrit but an unaltered hemoglobin concentration. In combination with data in the literature our studies suggest that the initial CBF increase is a consequence of a transient extracellular acidosis dilating brain arterioles, whereas increased ventilatory drive results from a gradually increasing mild intracellular acidosis in the brain.

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