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| 1 | D-galactosamine based canine acute liver failure model显示文摘Background: Appropriate preclinical evaluation of abioartificial liver assist device (BAL) demands alarge animal model, as presented here, that demon-strates many of the clinical features of acute liverfailure and that is suitable for clinical qualitative andquantitative evaluation of the BAL. A lethal canineliver failure model of acute hepatic failure that re-moves many of the artifacts evidenced in prior caninemodels is presented.Methods: Six male hounds, 24-30 kg, under isoflu-rane anesthesia, were administered 1.5 g/kg D-galactosamine intravenously. Canine supportive carefollowed a well-defined management protocol thatwas guided by electrolyte and invasive monitoringconsisting of arterial pressure, central venous pres-sure, extradural intracranial pressure (ICP), pul-monary artery pressure, and end-tidal CO2. Theanimals were treated until death-equivalent, definedas inability to sustain systolic blood pressure>80mmHg for 20 minutes despite maximal fluids and 20μg·kg-1·min-1 dopamine infusion.Results: The mean survival time was 43.7±4.6hours (mean±SE). All animals showed evidence ofprogressive liver failure characterized by increasingliver enzymes (aspartate transaminase from 26 to5977 IU/L; alanine transaminase from 32 to 9740IU/L), bilirubin (0.25 to 1.30 mg/dl), ammonia(19. 8 to 85. 3 μmol/L), and coagulopathy (pro-thrombin time from 8.7 to 46 s). Increased labilityand elevations in intracranial pressures were ob-served. All animals were refractory to maintenanceof cerebral perfusion pressure even with only mode-rately elevated intracranial pressure. Severe neuro-logic obtundation, seen in 2 of 6 animals, was associ-ated with elevations of ICP above 50 mmHg. Post-mortem liver histology showed evidence of massivehepatic necrosis. Postmortem blood and ascites mi-crobial growth was consistent with possible transloca-tion of intestinal microbes.Conclusions: The improved lethal canine liver failuremodel presented here reproduces many of the clinicalfeatures of acute liver failure. The model may proveuseful for qualitative and quantitative evaluation ofBALs. | JohnF.PatzerⅡ GeoffreyD.Block AjaiKhannaErnestoMolmenti DavidGerber DavidJ.Kramer VictorL.Scott ShushmaAggarwal RobertA.Wagner MelissaL.Fulmer BruceP.Amiot GeorgeV.Mazariegos | 2002 | Hepatobiliary & Pancreatic Diseases International2002，1，3： | 3 |
| 2 | A reliable graded acute liver failure model in rats: treatment with internal bioartificial liver显示文摘BACKGROUND: Appropriate animal models are impor- tant for studying acute liver failure. This study was to assess a new suitable rat model for acute liver failure. METHODS: After the right influent hepatic vessels were clamped for a period of time (45, 60 or 90 minutes respec- tively), the animal model was established by removal of the clamp for restoring blood flow of the right lobes while im- mediately removal of the median, left lateral and caudate lobes. Animal survival rate was observed in the following 14 days in each group. To study the pathophysiological chan- ges of the model, some biochemical parameters in 5 con- secutive days were evaluated in the 60-minute group. Inter- nal bioartificial liver was transplanted in the peritoneal cavi- ty to test the reversibility of the model. RESULTS: The survival rate of the models decreased, as the ischemia time of the right lobes prolonged to zero in the 90-minute group, to 50% in the 60-minute group and to 100% in the 45-minute group on the fifth day after opera- tion. The levels of ammonia, alanine aminotransferase, al- kaline phosphatase, total bilirubin and prothrombin were elevated dramatically 12 to 24 hours after operation in the 60-minute group. When internal bioartificial liver was transplanted, the survival rate increased significantly in ad- dition to the levels of ammonia and total bilirubin. CONCLUSION: A period time of ischemic injury in the right lobe followed by 70% liver resection can produce a graded acute hepatic failure model in rats. | Qing-Xiang Xu, Yi-Tao Ding, Yu-Dong Qiu, De-Cai Yu and He-Yuan Zhang Nanjing, China Department of Hepatobiliary Surgery, Drum Tower Hospital, Medical College of Nanjing University, and Hepatobiliary Institute of Nanjing University Hepatobiliary Surgery Institute of Nanjing Biochemistry Department of Nanjing University, Nanjing 210008 , China | 2004 | Hepatobiliary & Pancreatic Diseases International2004，3，2： | 0 |
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