Novel Bioartificial Liver Support System: Preclinical Evaluation

作者：John F. Patzer, George Vincent Mazariegos, Roberto López, Ernesto P. Molmenti, David Allen Gerber, FRIDTJOV RIDDERVOLD, AJAI KHANNA, Wen‐Yao Yin, Yong Chen, Victor L. Scott, S Aggarwal, David J. Kramer, Robert A. Wagner, Yue Zhu, Melissa L. Fulmer, Geoffrey D. Block, Bruce P. Amiot · 发表于：Annals of the New York Academy of Sciences · 年份：1999 · DOI：10.1111/j.1749-6632.1999.tb08516.x · 被引用次数：72 · 研究领域：Organ Transplantation Techniques and Outcomes、Liver Disease and Transplantation、Liver physiology and pathology

Preclinical safety and efficacy evaluation of a novel bioartificial liver support system (BLSS) was conducted using a D-galactosamine canine liver failure model. The BLSS houses a suspension of porcine hepatocytes in a hollow fiber cartridge with the hepatocytes on one side of the membrane and whole blood flowing on the other. Porcine hepatocytes harvested by a collagenase digestion technique were infused into the hollow fiber cartridge and incubated for 16 to 24 hours prior to use. Fifteen purpose-bred male hounds, 1-3 years old, 25-30 kg, were administered a lethal dose, 1.5 g/kg, of D-galactosamine. The animals were divided into three treatment groups: (1b) no BLSS treatment (n = 6); (2b) BLSS treatment starting at 24-26 h post D-galactosamine (n = 5); and (2c) BLSS treatment starting at 16-18 h post D-galactosamine (n = 4). While maintained under isoflurane anesthesia, canine supportive care was guided by electrolyte and invasive physiologic monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, urinary catheter, and end-tidal CO2. All animals were treated until death or death-equivalent (inability to sustain systolic blood pressure > 80 mmHg for 20 minutes despite massive fluid resuscitation and/or dopamine administration), or euthanized at 60 hours. All animals developed evidence of liver failure at 12-24 hours as evidenced by blood pressure lability, elevated ICP, marked hepatocellular enz...