一种用于评估暴发性肝衰竭生物人工肝支持系统的实验性大型动物模型。

An experimental large animal model for the assessment of bioartificial liver support systems in fulminant hepatic failure.

作者信息

Ytrebø L M, Nedredal G I, Langbakk B, Revhaug A

机构信息

Dept of Digestive Surgery, University Hospital Northern Norway, Tromsø.

出版信息

Scand J Gastroenterol. 2002 Sep;37(9):1077-88. doi: 10.1080/003655202320378293.

DOI:10.1080/003655202320378293

PMID:12378705

Abstract

BACKGROUND

Pre-clinical assessment of bioartificial liver support systems requires a highly reproducible large animal model. The main objective of the present study was to develop a valid large animal model for assessing novel bioartificial liver support systems in fulminant hepatic failure.

METHODS

A complete liver devascularization procedure was performed in 10 female pigs weighing 25-38 kg. Five matched pigs were sham-operated and served as controls.

RESULTS

Pigs with fulminant hepatic failure developed a hyperdynamic circulation, with increased cardiac index (P(GT) < .0001), decreased systemic vascular resistance index (P(GT) < .0001) and mean arterial pressure (P(GT) = .001). Furthermore, intracranial hypertension developed (P(GT) < .0001). with increased common carotid artery flow (P(GT) < .0001) and decreased common carotid resistance (P(G) = .003). Femoral artery flow increased (P = .036). while hindleg resistance (P < .001) and renal artery resistance decreased (P = .019). Oxygen consumption (P(GT) = .050) and oxygen extraction ratio (P(GT) = .001) increased compared to controls. Arterial ammonia, venous aspartate aminotransferase and bilirubin levels increased (P(GT) < .0001, respectively). Abnormal haemostasis developed with significant loss of platelets (P(GT) = .010), decreasing fibrinogen levels (P(G) = .001) and increasing international normalized ratio (P(GT) = .012) and activated clotting time (PGT < .001). Urine became hypo-osmotic (P < .001. P(G) = .011), with decreased sodium levels (P = .08) and increased potassium levels (P(G) = .025).

CONCLUSIONS

This study characterizes a reproducible large animal model for fulminant hepatic failure that seems suitable for the assessment of bioartificial liver support systems.

摘要

背景

生物人工肝支持系统的临床前评估需要一个高度可重复的大型动物模型。本研究的主要目的是建立一个有效的大型动物模型，用于评估暴发性肝衰竭中的新型生物人工肝支持系统。

方法

对10头体重25 - 38 kg的雌性猪进行完全肝去血管化手术。5头匹配的猪进行假手术并作为对照。

结果

暴发性肝衰竭的猪出现高动力循环，心脏指数增加（P(GT) <.0001），全身血管阻力指数降低（P(GT) <.0001），平均动脉压降低（P(GT) =.001）。此外，出现颅内高压（P(GT) <.0001），颈总动脉血流增加（P(GT) <.0001），颈总动脉阻力降低（P(G) =.003）。股动脉血流增加（P =.036），而后肢阻力降低（P <.001），肾动脉阻力降低（P =.019）。与对照组相比，氧耗量（P(GT) =.050）和氧摄取率增加（P(GT) =.001）。动脉血氨、静脉天冬氨酸转氨酶和胆红素水平升高（分别为P(GT) <.0001）。出现异常止血，血小板显著减少（P(GT) =.010），纤维蛋白原水平降低（P(G) =.001），国际标准化比值增加（P(GT) =.012），活化凝血时间延长（PGT <.001）。尿液变为低渗（P <.001，P(G) =.011），钠水平降低（P =.08），钾水平升高（P(G) =.025）。