The Effect Of Propofol Metabolism In Crab-eating Monkeys With Hepatic Fibrosis At Different Phases

Objective: The objective was to make a model of different degree hepaticfibrosis in Crab-Eating monkeys and establish a method HPLC to determineplasma concentration of propofol to assay the plasma concentration and theawaking-time of Crab-Eating monkeys, in order to reveal the metabolismeffect of propofol on different stages of liver fibrosis. It would also providetheoretical and experimental evidences for anesthetization of patients with liverfibrosis and chronic liver disease.Method: Twenty healthy male Crab-Eating monkeys, aged6-7years,weighting6-7kg. The model was established by using subcutaneous inject CCl4at beginning, twice per week. At the third week, assisting high fat diet anddrinking alcohol, divided into pre-model group (M0), the4th weekend group(M1), the8th weekend group (M2), modeling12th weekend group (M3), the16th weekend group (M4))；The dosage for continuous intravenous transfusion of propofol was15mg/kg/h and to last60minutes after anesthetized30minutesby intramuscular injection with Ketamine Hydrochloride injection, MidazolamInjection and Scopolamine Hydrobromide Injection, and then mask oxygeninhalation, transfuse，detect electrocardio, blood pressure, respiration and so on.Blood sample for hepatic function detection was taken before using propofol,hepato-pathological examinations by mode ultrasound B at the process ofinjecting propofol, to determine the stages of the corresponding pathology andmake it internalize the stage S0、S1、S2、S3、S4. Using HPLC to detect plasmaconcentration of propofol at the time of2min,5min,10min,30min,60min andawaking-time in different stages, noting the awaking-time of Crab-Eatingmonkeys. After two days of liver biopsy, taking two Crab-Eating monkeys ineach stage, anesthetizing Crab-Eating monkey by above-mentioned anesthetic,then made it shift to operating table and fixed it by resupination. Takingabdomen median incision，liberating main portal vein, and make the catheterinsert into the portal vein, then link the pressure transducers named YP100andbiology function experiment system and computer, assaying the free portalpressure, at last executing the animal.Results: The body weight of Crab-Eating monkeys was abatementgradually and activity was decreased as the time extended of model. The stageof S0was20, S1was16, S2was13, S3was10, S4was7according to thepathology staging; liver function: the TP and A/G were changed obviously, total protein cut down gradually, even the A/G stand upside down, the TP and A/Gsignificantly lower in the stage S4than that in stage S3, S2, S1and S0(P<0.05),there are have the statistical significance; The comparison of awaking-time: theawaking-time of Crab-Eating monkeys was extended as the aggravation of liverfibrosis, The awaking-time was prolonged in the stage S4than that in stage S3,S2, S1and S0(P<0.05); The comparison of plasma concentration: carried out thepeak area ratio（Ai/As） of propofol and thymol with concentration(C) ofpropofol to linear regression and received the standard regression equation:Ai/As=0.23C-0.045（r=0.995,n=5），The plasma concentration was calculated bythe formula of above-mentioned，Thus it can be seen the plasma concentrationwas no obviously changes at the awaking-time, but at the other times, the stageof S4increased significantly(P<0.05).however, comparing between the S3、S2、S1、S0period,the difference have no statistics significantly. The comparison offree portal pressure: the free portal pressure was higher along with the hepaticfibrosis become more serious, until the late stage of hepatic fibrosis, the pressureof portal vein in Crab-Eating monkeys were increase to three times before themodel was building.Conclusions： The early stage hepatic fibrosis not affect the metabolism ofpropofol, but along with the hepatic fibrosis is exacerbation, hepatic functiondecreased obviously, the metabolism of propofol is slow down, until the stage ofS4, the awakening time of Crab-Eating monkey is prolonged significantly.