Acute effects of acetazolamide on cerebral blood flow in man

We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i.v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PCO2, arterial PCO2, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75% increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the CO2 reactivities, given as delta CBF/delta PACO2 in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PACO2 level. The present dose of the drug caused no change in ventilation, alveolar and arterial PCO2 or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PCO2's. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.