Influence of Acetazolamide on Cerebral Blood Flow

Abstract

Carbonic anhydrase inhibitors have been used in clinical medicine as diuretics,1-3 as anticonvulsants,4,5 to reduce intraocular tension,6,7 to lower intracranial pressure,8,9 and in the treatment of respiratory insufficiency.10,11 In the course of investigation of the effects of acetazolamide in hepatic encephalopathy, Posner and Plum 12 observed without comment a considerable increase in rate of cerebral blood flow after intravenous administration of 1 to 2 gm. of acetazolamide. Such a cerebral circulatory change had previously been considered to account for the brief elevation of cerebrospinal fluid pressure after intravenous acetazolamide.9,13In view of these findings, we felt that the usefulness of carbonic anhydrase inhibitors might be extended to the management of patients with intermittent cerebral vascular insufficiency. In this preliminary report, observations of the quantitative cerebral hemodynamic effects of intravenous acetazolamide are presented. In several subjects, the effects of inhalation of 5% CO2 were also noted for comparative purposes. MethodThe subjects of this investigation were 10 pa¬ tients hospitalized for clinical study of cerebral vascular disease believed to be the cause of cir¬ culatory insufficiency of internal carotid or vertebral-basilar artery systems. In all cases, the disorder was manifested by recurrent, transitory neurological dysfunction, considered on clinical grounds to involve the cerebral areas primarily supplied by the arterial systems noted, and assumed to be due to intermittent ischemia of these areas.Cerebral hemodynamic studies were performed before and 30 to 60 minutes after the intravenous administration of 1 gm. of acetazolamide (2 gm. in one instance) over a 10-minute period. In 8 of these patients, the effects of inhalation of S'%

The Effect of Acetazolamide on Cerebral Blood Flow and Oxygen Utilization in the Rhesus Monkey

“…The most obvious indication of this during our experiments was an immediate fall in end-tidal Pco2 to -50% of normal after acetazolamide administration. Both our work and that of others (Table I, [1][2][3] suggest the acetazolamide-induced hypercapnia is only partly responsible for the increase in CBF observed. Statistical correction of our CBF data for the Paco2 increase reduces the observed CBF increase from 29.2 to 15.4%.…”

“…We have reexamined the effect of acetazolamide on CBF and although we observed an increase, it was consistently less than the large increases in CBF others have reported (1)(2)(3)(4)(5)(6)(7). This apparent discrepancy prompted us to measure the effect of acetazolamide on the CMRO2 because the reported CBF changes after intravenous acetazolamide (Table I) are based, in large measure, on the use of the brain arteriovenous oxygen difference as an index of CBF.…”

“…Control Paco2 was varied over the range shown by mild hypo-or hyperventilation and (or) ventilation with gas mixtures containing 5 or 10% carbon dioxide balanced with oxygen. The equations for the regression lines and 95% confidence intervals of the slopes and intercepts 2 Raichle, M. E. Unpublished observations. FIGURE 2 The change in miiean CBF anid meani Paco2 after intravenious admiinlistrationi of acetazolamide in rhesus miionikeys.…”

“…The equations for the regression lines and 95% confidence intervals of the slopes and intercepts 2 Raichle, M. E. Unpublished observations. FIGURE 2 The change in miiean CBF anid meani Paco2 after intravenious admiinlistrationi of acetazolamide in rhesus miionikeys. The The resulting a-v oxygen difference is 56.5% of control, which is a significant difference (P < 0.00001).…”

“…We have found an excellent correlation between oxygen content of blood taken with this appliance from this site and jugular bulb oxygen content in the rhesus monkey, directly supporting the contention that this represents cerebralmixed venous blood. 2 Monkeys used for more than one experiment were allowed to recuperate for a minimum of 2 wk between procedures. Radioisotope detectiotn and data collection.…”