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Changes in Rocuronium Pharmacodynamics and Renal Oatp-3 Related Rocuronium Metabolism in Rat Anhepatic Phase

Author: ChenYiFei
Tutor: TaoGuoCai
School: Third Military Medical University
Course: Anesthesiology
Keywords: rocuronium pharmacodynamics anhepatic phase oatp-3 RT-PCR western blot
CLC: R614
Type: Master's thesis
Year: 2006
Downloads: 47
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Abstract


Objective: Rocuronium is one of muscle relaxant most commonly used in liver transplantation.It is metabolized mainly by liver and then discharged in prime type by biliary passage system.Recent studies show that although the metabolism of rocuronium by liver is absent in the anhepatic phase during liver transplantation,its metabolism is not affected obviously,suggesting the existence of extrahepatic metabolism and an enhanced extrahepatic metabolism of rocuronium in the anhepatic phase.But this postulation is to be confirmed.In normal,rocuronium is transported into cell mainly by oatp distributed in liver then discharged in prime type by biliary passage system.The organic anion-transporting polypeptides （OATP） represent a family of proteins responsible for the membrane transport of a large number of endogenous and xenobiotic compounds with diverse chemical characteristics. OATPs are expressed in liver, kidney, brain and intestine suggesting that they play a critical role in drug disposition.The oatp expression level is modulated in tissue-specific and environment-related manner.In the anthepatic phase of liver transplantation,internal milieu changes drastically,and the levels of some hormones may affect the expression of oatp,thus influencing extrahepatic metabolism of rocuronium. In this study rocuronium pharmacodynamics in anthepatic rats was studied,and the changes in kidney oatp-3 and its gene expression were investigated.This study was designed to preliminarily elucidate the changes by which the anhepatic state influences the oatp expression and the mechanism of rocuronium pharmacokinetics in the anhepatic phase.Materials and Methods: This study is composed of three parts:Part 1.Verification of small animal automatic respirator which made by ourself.10 health male SPF SD rat were etherized and their right internal carotid artery was incised and inserted with a 1.0 gauge silicone tube.then,incised the trachea,inserted with a gauge silicone which diameter is 1.5 mm.ligated to keep air passage close tightly. respirator Setted as VT（tidal volume） 1012 ml/kg;respiratory frequency 7585 cpm;FiO2 1.0;inspiratory/expiratory=1:1.During experiment, rat temperature was kept between 36℃and 37℃.And then 0,5,10,20,40,60 min after mechanical ventilation,0.3ml of boold sample was drawn from the right internal carotid

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