Usual clinical dose of acetazolamide does not alter cerebral blood flow velocity

Abstract

Prior reports indicate that acetazolamide, an inhibitor of carbonic anhydrase, in moderate doses reduces symptoms of acute mountain sickness, and in large dose increases cerebral blood flow. The effect on flow is not known for a moderate dose, but were flow to increase, then increased cerebral cortex oxygen delivery would be one mechanism of benefit from acetazolamide at high altitude. We utilized Doppler ultrasound in 8 volunteers to determine whether a usual acetazolamide dose (250 mg three times daily) would increase flow velocities in internal carotid and vertebral arteries. Acetazolamide during normoxia decreased pHa, Pa CO 2 , and P ET CO 2 , but baseline flow velocity remained unchanged. In 2 subjects without acetazolamide, voluntary hyperventilation decreased both P ET CO 2 and flow velocity. Both hypoxia and hypercapnia caused increases in arterial velocities. The increases were not altered by acetazolamide administration. In one sybject, 1 g acetazolamide by acute i.v. injection induced an increase in flow velocity (40%) concomitant with a 5 mm decrease in P ET CO 2 confirming prior reports using similar intravenous dose. In doses employed for prevention of acute mountain sickness, acetazolamide induced metabolic acidosis and may have prevented the fall in velocity usually associated with hypocapnia, but it neither increased baseline cerebral blood flow velocity nor velocity responses to hypoxia and hypercapnia. Benefit of acetazolamide at high altitude may related to mechanisms other than increased cerebral blood flow.