Quantitative EEG changes due to cerebral vasoconstriction. Indomethacin versus hyperventilation-induced reduction in cerebral blood flow in normal subjects.

Hyperventilation leads to an increase in slow EEG activity as well as to a decrease in alpha activity. These effects may be considered a result of reduction in cerebral blood flow due to vasoconstriction, but metabolic factors, such as alkalosis and the increased formation of cerebral lactate, may also have to be taken into account. As indomethacin decreases cerebral blood flow it is possible to study cerebral vasoconstriction, without concomitant metabolic alkalosis or cerebral lactate formation. Two parallel groups of 12 healthy male subjects (age 20-25) were studied with quantitative EEG (qEEG) and cerebral blood flow velocity as parameters. In the first group the effect of 100 mg indomethacin was studied. In the parallel group a standardized hyperventilation procedure was performed. In the indomethacin group the blood flow velocity decreased to 60% of the initial value; the qEEG showed a 0.5 Hz slowing of the alpha peak frequency (P less than 0.01) and a decrease in the power of the alpha band without any change in the delta or theta band. In the hyperventilation group the blood flow velocity decreased to 63% of the initial value and the qEEG showed a marked increase in delta and theta activity (P less than 0.01), but a non-significant change in alpha peak frequency. Indomethacin and hyperventilation caused similar degrees of vasoconstriction; however, the increase in qEEG slow wave activity, which was observed only in the hyperventilation group, is apparently related to metabolic rather than haemodynamic factors.

Quantitative EEG during progressive hypocarbia and hypoxia. Hyperventilation-induced EEG changes reconsidered.

To investigate the role of cerebral hypoxia as a causative factor in the alteration of the qEEG during hyperventilation, qEEG changes caused by progressive hypocapnia were compared with qEEG changes due to progressive normobaric hypoxia in two parallel groups of 12 and 10 healthy male subjects (age 20-27 years), respectively. In the first group, qEEG records were obtained before and during hyperventilation to pCO2 levels of 4.0, 3.0 and 2.0 kPa. In the second group, the qEEG samples were taken before and during hypoxia with hemoglobin oxygen saturations of 80, 70 and 60%. In both groups, blood flow velocity in the middle cerebral artery was also recorded. Hyperventilation caused an exponential increase in slow activity and a decrease in alpha power. No shift in the alpha mean frequency and alpha peak frequency was observed, except with the pCO2 level of 4.0 kPa, which caused an increase in both variables. Hypoxia with a hemoglobin oxygen saturation of 60% caused a much less pronounced increase in slow activity. No change in total power in the alpha band was found, but both the alpha peak frequency and alpha mean frequency decreased. Lesser degrees of hypoxia caused only minimal EEG changes. Blood flow velocity was decreased by hyperventilation but increased by hypoxia. It is concluded that the EEG changes observed during hyperventilation must mainly or totally be attributed to factors other than cerebral hypoxia.

Nimodipine tested in a human model of cerebral ischaemia. Electroencephalographic and transcranial Doppler ultrasound investigations in normal subjects during standardized hyperventilation.

The anti-ischaemic properties of nimodipine 30 mg and 60 mg t.i.d. for 4 days has been tested in a double-blind, placebo-controlled, cross-over study based on the use of hyperventilation to reduce flow velocity in cerebral arteries. Whether the anti-ischaemic properties were due to a vasodilatator action on cerebral blood vessels or to an anti-ischaemic effect on cerebral neurons was studied. There was a slight cardiovascular effect, without any significant change in the EEG at rest. During standardized hyperventilation, there was no difference in the reduction in the blood flow velocity in the nimodipine and placebo groups (namely 56%, 56% and 59%). Both doses of nimodipine, however, significantly attenuated the hyperventilation-induced increase in slow EEG activity in the 1.5-6.0 Hz range. It is concluded that the anti-ischaemic properties of nimodipine are due to an effect on the central nervous system rather than to an effect on cerebral blood flow.

A pharmacological model of cerebral ischemia. The effects of indomethacin on cerebral blood flow velocity, quantitative EEG and cognitive functions.

Indomethacin decreases cerebral blood flow. Such an effect in humans might offer the possibility to establish a human model of cerebral ischemia. In the present study the effects of a single oral dose of 100 mg indomethacin were studied in male subjects with quantitative electroencephalography, cerebral blood flow velocity and the memory comparison task as parameters. Twelve healthy male students (age 23.2 +/- 2.6 years) were studied. Before the test day the memory comparison task was performed twice (parallel versions). On the test day baseline recordings of quantitative electroencephalography were obtained, together with measurement of blood flow velocity. Ninety minutes after indomethacin ingestion recordings of quantitative electroencephalography and blood flow velocity were repeated and a parallel version of the memory comparison task was performed. The blood flow velocity decreased to 60% of the initial value; quantitative electroencephalography showed a -0.3 Hz slowing of the alpha peak frequency (p less than 0.01) and a decrease in the relative power of the alpha band (p less than 0.10) without any change in the delta or theta band. The memory comparison task showed an increase of the slope index (p less than 0.05), indicating a deterioration of cognitive functioning.

1H and 31P NMR measurement of cerebral lactate, high-energy phosphate levels, and pH in humans during voluntary hyperventilation: associated EEG, capnographic, and Doppler findings.

In order to explore the sensitivity of spatially resolved 1H and 31P NMR spectroscopy on a whole-body NMR instrument, cerebral metabolic changes in human volunteers were measured during hyperventilation provocation. During hyperventilation the flow velocity in the middle cerebral artery decreased significantly and the EEG showed a marked increase in slow activity. 1H NMR spectra revealed an increase in cerebral lactate concentration. 31P NMR spectra showed no changes in ATP or PCr peak heights, but a shift toward tissue alkalosis was derived from changes in Pi chemical shift. During subsequent recovery, lactate concentration decreased and a slight intracellular acidosis was detected. In three experiments broadening of the lactate resonance peak resulted in separation into two components at 1.32 and 1.48 ppm, in which the latter signal possibly arose from alanine.

The hyperventilation-induced ischaemia model in human neuropharmacology: neurophysiological and psychometric studies of aniracetam and 3-OH aniracetam.

Standardized hyperventilation in young subjects induces changes in the EEG, a decrease in the velocity of the cerebral blood flow and a decline in cognitive performance, which are comparable to those occurring in patients with cerebral ischaemia. The anti-ischaemic properties of aniracetam and 3-OH aniracetam were tested in this model. A single oral dose of 3-OH aniracetam 1500 mg appeared to have the most pronounced effect on hyperventilation-induced EEG changes and cognitive deterioration. The test drugs had no effect on the heart rate or blood flow velocity. The effects agree with those of other drugs classified as noötropics.

Transcranial pulsed Doppler measurements of blood velocity in the middle cerebral artery: reference values at rest and during hyperventilation in healthy volunteers in relation to age and sex.

Transcranial pulsed Doppler analysis of blood velocity in the middle cerebral artery was performed in 120 healthy volunteers (age 20-70 y, 12 male and 12 female subjects per decade), meeting strict selection criteria. The intention was to create normative reference data, both at rest and during hyperventilation, for the assessment of abnormality in patients with cerebral vascular disorders. The measured blood velocity at rest decreased significantly with increasing age. Females up to 50 years of age had significantly higher blood velocity values than males. Blood velocity diminution was induced by means of voluntary hyperventilation, under capnographic control. An age related decline of blood velocity as present at rest was not found during hyperventilation, thus the relative value of hyperventilation induced changes diminished with increasing age. The pCO2 related change in the blood velocity index appeared not to be a constant value, as suggested by previous authors. The blood velocity index was largest in the change from resting condition to 4 kPa pCO2, and smallest in the change 3 kPa pCO2 to 2 kPa pCO2. When examining the blood velocity in the MCA, the age, sex and end-tidal pCO2 pressure have to be taken into account for a correct interpretation of the data obtained.

Changes in quantitative EEG and blood flow velocity due to standardized hyperventilation; a model of transient ischaemia in young human subjects.

A standardized hyperventilation (HV) procedure has been developed in which the end-tidal pCO2 was decreased to 2 kpa. In 24 young male subjects blood flow velocity and qEEG were studied before, during and after HV. This standardized hyperventilation procedure gave rise to a decrease in blood flow velocity to 40% of baseline value and highly significant qEEG changes in 3 derivations. Both relative and absolute band power estimates showed an increase in slow activity and a decrease in alpha and beta activity. The use of subtraction spectra led to a more precise and detailed presentation of these changes than the use of classical qEEG parameters. These changes were reproducible after 1 week. The effects found in the presented model of HV-induced ischaemia appeared to be twice as large as those found in a model of hypobaric hypoxia. The present model might be used to test the efficacy of anti-ischaemic drugs in young human subjects.

Quantitative EEG changes due to hypobaric hypoxia in normal subjects.

A condition of hypobaric hypoxia was created in a low pressure chamber by reducing the atmospheric pressure to 46.5 kPa. Thirty-six subjects were exposed to hypobaric hypoxia during 19 min with a recovery period of 25 min. In 13 subjects the experiment was repeated after 1 week. Four EEG channels, HbSaO2, PeCO2, heart and respiration rate were continuously monitored. Quantitative EEG (qEEG) samples for the derivation P4-O2 were taken in normobaric normoxic (A), hypobaric normoxic (B) and hypobaric hypoxic (C) conditions and mutually compared. Subtraction spectra and standard qEEG parameters were studied, in an attempt to select those which are most reliable to detect hypoxia. Hypobaric normoxia caused no significant qEEG changes. Hypobaric hypoxia resulted in a significant increase in slow activity, a significant decrease in alpha activity and a non-significant decrease in beta activity. Two clusters of non-related standard qEEG parameters were found to be sensitive to hypoxia. The differences between the parameters within each cluster are too small to permit a definite choice of one of them. For the description of qEEG changes due to hypoxia at least one parameter from each cluster has to be taken into account.