ABSTRACT
BACKGROUND: Acetazolamide (AA) is used to determine the cerebral vasoreactivity (CVR). To investigate whether the usually applied standard dose of 1 g intravenously will guarantee stable test conditions, the dose-response relationship of AA on cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) in normal subjects was determined. METHODS: In 59 healthy volunteers, rCBF was measured with a (133)Xenon inhalation device, and CBFV of the middle cerebral artery (MCA) by transcranial Doppler sonography. The first CBF measurement was taken at rest, the second 15 min after application of AA at a dosage of 5, 10, 13, 15 and 18 mg/kg of body weight, respectively. The CBFV (n = 52) of the middle cerebral artery on the side of the better temporal window was taken 25 min after application of AA 13 mg/kg. In order to determine the side effects of AA, statements of an additional 172 patients were included. RESULTS: A significant dosage dependence of AA on the CBF (fast flow and initial slope index) exists between 5 and 18 mg/kg intravenously. After AA 13 mg/kg, the fast flow increases from 70.8 +/- 10.8 to 110.1 +/- 13.5 ml/100 g/min, the initial slope index from 46.5 +/- 5.4 to 62.8 +/- 5.8, and the CBFV from 51.5 +/- 8.5 to 85.4 +/- 14.2 cm/s. The CVR of CBF and CBFV ascertained that way shows an age dependence equivalent to the situation at rest. Severity and frequency of side effects are dosage-dependent, significantly in part, but reversible without exception. CONCLUSION: For the determination of CVR of CBF with AA, a dosage related to body weight is required. The usually applied standard dose of 1 g intravenously is not sufficient for standardized test conditions. For evaluation of the results obtained, the apparent age dependence of CVR must be taken into account. Because of the severity of side effects occurring at a higher dose, an AA dosage of 13 mg/kg intravenously is recommended.
Subject(s)
Acetazolamide/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Cerebrovascular Circulation/drug effects , Acetazolamide/adverse effects , Acid-Base Equilibrium/drug effects , Adolescent , Adult , Aged , Aging/physiology , Blood Gas Analysis , Blood Pressure/drug effects , Blood Pressure/physiology , Body Weight/physiology , Carbonic Anhydrase Inhibitors/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Ultrasonography, Doppler, Transcranial , Xenon RadioisotopesABSTRACT
After a wash-out period of four weeks 51 patients with mild to moderate senile dementia were treated with either 600 mg naftidrofuryl (n = 23) daily per os or placebo (n = 28) over an eight-week period. When classified according to Hachinski's score, 24 patients were found to be suffering from senile dementia of Alzheimer's type (SDAT), whereas 27 patients presented with vascular dementia (MID). During wash-out and the treatment period the somatic and social symptoms of the disease were assessed by the AGP score. Cerebral performance was evaluated by a battery of tests measuring memory, concentration, psychomotor coordination and degree of depression. Electrical activity of the brain was estimated by a power-spectral analysis of EEG. In the total study group, the naftidrofuryl group showed a significantly better improvement in the results of the psychometric test battery, which was the primary variable during treatment. A parallel development was to be found in the AGP score and electrical brain function. When results of subgroups were analyzed according to the etiopathogenetic background of patients with SDAT, it was possible to show that naftidrofuryl affected psychopathometry and EEG-parameters while patients with MID responded to naftidrofuryl with changes in AGP score and EEG variables. These findings indicate the importance of etiopathologic features in performing studies with nootropic drugs in obtaining information on possible different actions in patients with different kinds of senile dementia.