Acute effects of acetazolamide on cerbral blood flow in man

Abstract

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.

Arterial Spin-Labeling Evaluation of Cerebrovascular Reactivity to Acetazolamide in Healthy Subjects

“…Such a detailed assessment of the time course of CBF changes is difficult with the use of methods requiring administration of exogenous contrast agents or radiotracers. Doppler ultrasonography 17,18 and phase-contrast MR imaging 19 have been used to assess the time course of cerebrovascular response to ACZ and have shown temporal changes in blood flow or velocity in the major cerebral arteries that are consistent with temporal changes in rCBF observed in the current study. Planar dynamic imaging after radio-labeled albumin has also revealed similar temporal patterns in alterations of cerebral blood volume representing intravascular volume.…”

“…2,13 Previous studies with the use of Doppler ultrasonography demonstrated increased blood velocity after ACZ injection in the MCA 17 and internal carotid artery. 18 The administration of ACZ may shorten the arrival time as a result of increased blood velocity and aid early influx of labeled water into the brain tissues, which may enhance ASL signals with a short PLD preferentially and consequently cause overestimation of CVR. The mean CVR values reported in normal subjects range from 25-31% with the use of 133 Xe inhalation SPECT, 18,21-23 from 33.5-35% with the use of 15 O-water positron-emission tomography, 24,25 and from 37.7-54.2% with the use of ASL MR imaging.…”

Is the Acetazolamide Test Valid for Quantitative Assessment of Maximal Cerebral Autoregulatory Vasodilation?

“…[2][3][4] Intravenous doses of 7 to 30 mg/kg ACZ in rats 1,5 and 0.5 to 1 g in humans [2][3][4]6 produce no or little change in blood pressure and an increase in cerebral blood flow (CBF), so that cerebral vascular resistance (CVR) decreases. In clinical investigation, this decrease in CVR in response to ACZ injection is often considered a surrogate of the decrease in CVR elicited by hypotension (ie, autoregulatory vasodilation).…”

An evaluation of the plethysmographic method of measuring cranial blood flow in the new‐born infant.

“…The range of values usually obtained in a series of ten from one baby was much greater than we would expect as normal physiological variation (see Table 2 and Cross et al 1979). Continuous ultrasound recording of blood velocities in the internal carotid arteries in adults gives rather stable values (Hauge, Thoresen & Wall0e, 1980;Hauge, Nicolaysen & Thoresen, 1982).…”