Gonzales R A, McNabb J, Yim H J, Ripley T, Bungay P M
Institute for Neuroscience, Neuropharmacology Program, University of Texas, Austin 78712, USA.
Alcohol Clin Exp Res. 1998 Jun;22(4):858-67.
We have applied a steady-state theory of microdialysis to characterize the diffusion of ethanol through a microdialysis membrane and through rat striatum. Quantitative characterization required measurement of in vitro and in vivo extraction fractions for ethanol and determination of the clearance of ethanol from brain tissue during steady-state perfusion through a microdialysis probe. Extraction fraction of ethanol was determined in vitro by perfusing a known concentration of ethanol through probes immersed in water at 37 degrees C with stirring. The in vitro extraction fraction yielded a probe permeability value of 0.046 +/- 0.004 cm/min that is comparable with an estimate from published measurements for similar dialysis membranes. The in vivo extraction fraction was determined for probes placed in the striatum. Clearance of ethanol and a brain slice concentration profile of ethanol were determined by measurement of the amount of ethanol remaining in the brain tissue during steady-state perfusion of the probe. Steady state was achieved within 10 min after beginning the ethanol perfusion in vivo, and the extraction fraction was not altered by sedation of the rat with pentobarbital. The tissue concentration profile was symmetrical around the probe track, and ethanol was detected 1 mm from the probe. The experimental clearance rate constant value obtained for ethanol (2.0 +/- 0.3 min(-1)) was higher than that expected for removal solely by loss to the blood. The tissue diffusivity for ethanol, Dt, derived from the experimental measurements was 1.2 +/- 0.2 x 10(-5) cm2/sec. This value is greater than expected for interstitial diffusion, suggesting a substantial contribution by transcellular diffusion of ethanol as well. The predicted tissue concentration profile had a higher peak value and did not extend into the tissue (0.5 mm) as much as the experimental profile (1 mm), although there was reasonable agreement between experiment and theory. Our quantitative characterization of the microdialysis behavior of ethanol in brain provides a framework for interpretation of brain microdialysis experiments using ethanol by supplying, inter alia, a means for estimating the ethanol concentration achieved in the tissue volume being sampled by the probe.
我们应用微透析的稳态理论来表征乙醇在微透析膜以及大鼠纹状体中的扩散。定量表征需要测量乙醇的体外和体内萃取分数，并在通过微透析探针进行稳态灌注期间测定乙醇从脑组织中的清除率。通过在37℃搅拌的条件下，将已知浓度的乙醇灌注到浸入水中的探针中来测定乙醇的体外萃取分数。体外萃取分数得出探针渗透率值为0.046±0.004 cm/min，这与已发表的类似透析膜测量估计值相当。体内萃取分数是针对置于纹状体中的探针测定的。通过测量在探针稳态灌注期间脑组织中剩余的乙醇量来确定乙醇的清除率以及乙醇的脑切片浓度分布。在体内开始乙醇灌注后10分钟内达到稳态，并且大鼠用戊巴比妥镇静不会改变萃取分数。组织浓度分布在探针轨迹周围是对称的，并且在距探针1 mm处检测到乙醇。乙醇获得的实验清除率常数（2.0±0.3 min⁻¹）高于仅因向血液中损失而清除的预期值。从实验测量得出的乙醇组织扩散系数Dt为1.2±0.2×10⁻⁵ cm²/秒。该值大于间隙扩散预期值，表明乙醇的跨细胞扩散也有很大贡献。尽管实验与理论之间有合理的一致性，但预测的组织浓度分布具有更高的峰值，并且没有像实验分布（1 mm）那样延伸到组织中（0.5 mm）。我们对乙醇在脑中微透析行为的定量表征为解释使用乙醇的脑微透析实验提供了一个框架，尤其通过提供一种估计探针采样的组织体积中达到的乙醇浓度的方法。
