Slow oscillations of cytochrome oxidase redox state and blood volume in unanesthetized cat and rabbit cortex. Interhemispheric synchrony.

The purpose of this study was to determine the frequency characteristics and the degree of interhemispheric synchrony of slow (< 0.5 Hz), spontaneous oscillations of the regional cortical cytochrome oxidase redox state (CYT) and blood volume (CBV) in unanesthetized animals. We implanted bilateral cortical windows and electrodes for polysomnography in 7 cats and 3 rabbits. The animals were atraumatically restrained during multiple 3-6 hour sessions for up to 8 weeks, and relative changes in the cortical CYT and CBV were monitored by dual wavelength reflectance spectrophotometry at 603 nm and 590 nm. Continuous oscillations of CYT and CBV, unrelated to pulse or respiration, were always observed in each animal. Frequency (FFT) analysis over time revealed a nonstationary distribution of frequencies below 0.4 Hz, with most of the spectral power being contained in the 0-0.25 Hz band during both waking and sleep. Although the time-frequency plots of the CYT and CBV signals were similar, an occasional dissociation between the CYT and CBV oscillations was found. Analysis of simultaneous bilateral cortical optical recordings revealed a significant and sustained interhemispheric cross-correlation over time between the CYT as well as the CBV oscillations during stable recordings as long as 60 min. We conclude that: 1) CYT and CBV levels normally oscillate at < 0.4 Hz in the unanesthetized cat and rabbit cortex; 2) these complex oscillations, whose frequencies are non-stationary over time, nevertheless show sustained interhemispheric synchrony between 50 mm2 homotopic cortical regions; and 3) these oscillations may in part represent fluctuations of the metabolic rate.

Interhemispheric synchrony of slow oscillations of cortical blood volume and cytochrome aa3 redox state in unanesthetized rabbits.

In order to study spontaneous, slow oscillations of regional oxidative metabolism and blood flow in the normal, unanesthetized cortex, adult rabbits were implanted with bilateral cortical windows and electrodes for polysomnography. Relative changes in the cortical intramitochondrial redox state of cytochrome aa3 (CYT) and blood volume (CBV) were monitored by dual-wavelength reflectance spectrophotometry. Continuous, non-stationary oscillations (< 0.5 Hz) of both CYT and CBV were observed during waking and non-REM sleep. Cross-correlation analysis revealed a predominant interhemispheric synchrony of these oscillations which were unrelated to the heart rate, breathing, or electrocorticogram pattern. These findings suggest a dynamic linkage of slowly varying metabolic and vascular processes between unanesthetized cortical regions of 50 mm2 surface area.

Low-frequency oscillations of cortical oxidative metabolism in waking and sleep.

To study the changes in cortical oxidative metabolism and blood volume during behavioral state transitions, we employed reflectance spectrophotometry of the cortical cytochrome c oxidase (cyt aa3) redox state and blood volume in unanesthetized cats implanted with bilateral cortical windows and EEG electrodes. Continuous oscillations in the redox state and blood volume (approximately 9/min) were observed during waking and sleep. These primarily metabolic oscillations of relatively high amplitude were usually synchronous in homotopic cortical areas, and persisted during barbiturate-induced electrocortical silence. Their mean amplitude and frequency did not vary across different behavioral/EEG states, although the mean levels of cyt aa3 oxidation and blood volume during rapid eye movement (REM) sleep significantly exceeded those during waking and slow-wave sleep. These data suggest the existence of a spontaneously oscillating metabolic phenomenon in cortex that is not directly related to neuroelectric activity. A superimposed increase in cortical oxidative metabolism and blood volume occurs during REM sleep. Experimental data concerning cerebral metabolism and blood flow that are obtained by clinical methods that employ relatively long sample acquisition times should therefore be interpreted with caution.

Carbamazepine-phenytoin interaction: elevation of plasma phenytoin concentrations due to carbamazepine comedication.

By intrapatient comparison at constant phenytoin (PHT) dose, the effect of carbamazepine (CBZ) comedication on PHT was studied in a group of 24 epileptic outpatients. In half of the patients with steady-state PHT plasma concentration, a significant increase of this concentration was noted after CBZ was added to their regimen. Twenty percent showed clinical manifestations of acute drug toxicity initially thought to be CBZ related. The mean PHT plasma concentration for the 12 patients (22.7 +/- 5.64 micrograms/ml) as well as concentration/dose ratio for PHT (4.61 +/- 1.65 micrograms/ml plasma per mg/kg/day dose) was significantly higher (p less than 0.001) with concomitant administration of CBZ than when PHT was given alone: PHT concentration, 12.54 +/- 3.93 micrograms/ml and PHT concentration/dose ratio, 2.52 +/- 0.78 micrograms/ml plasma per mg/kg/day dose. Those patients with higher PHT plasma concentrations seem to be at higher risk of PHT toxicity due to CBZ comedication.