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Determination of diffusion and partition coefficients of propofol in rat brain tissue: implications for studies of drug action in vitro Gredell J.A. , Turnquist P.A. , MacIver M.B. , Pearce R.A. British Journal of Anaesthesia Volume 93, Issue 6, Pages (December 2004) DOI: /bja/aeh272 Copyright © 2004 British Journal of Anaesthesia Terms and Conditions
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Fig 1 Uptake of propofol into brain slices. 300-μm-thick rat brain slices were incubated in ACSF containing 100 μM propofol for durations ranging from 7.5 to 480 min. The concentration in each slice was assessed by extraction and HPLC analysis. Each point represents the average of duplicate measurements from individual slices. The data were fitted by a monoexponential function with a time constant of 47 min. British Journal of Anaesthesia , DOI: ( /bja/aeh272) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions
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Fig 2 Determination of the diffusion coefficient for propofol in brain tissue. Average measured tissue concentrations normalized to the concentration at 360 min were plotted together with expected average tissue concentrations corresponding to a range of diffusion coefficients derived from a one-dimensional model of diffusion into both surfaces of a 300-μm-thick tissue slice. Each data point represents mean (sem) of eight brain slices (from Fig. 1). British Journal of Anaesthesia , DOI: ( /bja/aeh272) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions
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Fig 3 Depth–concentration profile of propofol in a 400-μm-thick brain slice. Tissue concentrations at depths from 50 to 400 μm are plotted for a drug with a diffusion coefficient of 0.02×10−6 cm2 s−1 diffusing into one surface of a brain slice (solid lines). Also plotted is the average concentration between depths of 25 and 200 μm (dashed line) and a monoexponential function with a time constant of 145 min and amplitude of 0.75 (dotted line). British Journal of Anaesthesia , DOI: ( /bja/aeh272) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions
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Fig 4 Slow onset of physiological effects of propofol in the hippocampus. (a) Evoked population spikes in the CA1 stratum pyramidale in response to paired electrical stimulation of stratum radiatum under control conditions, after 5 μM propofol had been applied for 300 min, and following addition of 100 μM picrotoxin. Calibration bar 50 ms, 4 mV. (b) Time course of development of effect of propofol on first (circles) and second (triangles) population spike amplitudes, normalized to the average amplitude during the 20-min control period. Population spike depression was rapidly reversed by the addition of 100 μM picrotoxin. British Journal of Anaesthesia , DOI: ( /bja/aeh272) Copyright © 2004 British Journal of Anaesthesia Terms and Conditions
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