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使用肝脏消除的弥散模型研究溶质在灌注大鼠肝脏中的停留时间分布:2. 药理试剂、逆行灌注以及酶抑制对伊文思蓝、蔗糖、水和牛磺胆酸盐的影响

Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 2. Effect of pharmacological agents, retrograde perfusions, and enzyme inhibition on evans blue, sucrose, water, and taurocholate.

作者信息

Roberts M S, Fraser S, Wagner A, McLeod L

机构信息

Department of Pharamcy, Otago Medical School, Dunedin, New Zealand.

出版信息

J Pharmacokinet Biopharm. 1990 Jun;18(3):235-58. doi: 10.1007/BF01062201.

Abstract

The effect of altered physiological conditions on the residence time distributions of sucrose, water, and taurocholate in the rat liver were studied using a bolus injection and quantifying fraction of total outflow per ml-time profiles. Retrograde perfusions increased the residence times of sucrose and water markedly and were associated with very low hepatic availabilities for taurocholate. Resistance by the inlet sinusoids sphincters, which become outlet sphincters during retrograde perfusions, is suggested as the explanation for the observation. Infusions of noradrenaline, propranolol, and lidocaine resulted in relatively small changes in the mean residence times for sucrose and water with no apparent relationship existing between the efficiency number of taurocholate and volumes of either water or sucrose. Taurochenodeoxycholate resulted in an increase in the availability and mean residence time for taurocholate relative to no infusion.

摘要

采用大剂量注射并通过每毫升时间曲线定量总流出分数的方法,研究了生理条件改变对大鼠肝脏中蔗糖、水和牛磺胆酸盐停留时间分布的影响。逆行灌注显著增加了蔗糖和水的停留时间,并且与牛磺胆酸盐的肝脏利用率非常低有关。在逆行灌注期间变为出口括约肌的入口窦状括约肌产生的阻力被认为是对此观察结果的解释。去甲肾上腺素、普萘洛尔和利多卡因的输注导致蔗糖和水的平均停留时间相对较小的变化,并且牛磺胆酸盐的效率数与水或蔗糖的体积之间没有明显关系。相对于未输注,牛磺鹅去氧胆酸盐导致牛磺胆酸盐的利用率和平均停留时间增加。

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