초록 |
Ammonia which shows perfusion-limited process in a bioartificial liver (BAL) system is converted into urea, following the enzymatic synthesis cycle. Ammonia removal rate under in vitro condition and in vivo application of the BAL was evaluated based on pharmacokinetics. Under in vitro condition, the clearance and intrinsic clearance of ammonia are 15 ml/min/module and 16.5 ml/min/module, respectively at the perfusate flow rate of 200 ml/min. For in vivo unhepatic dog model, the BAL system, which is consisted of the BAL cartridges, reservoir and dog, was supported by two BAL cartridges in a parallel circuit that contained total of 1x1010 porcine hepatocytes. The ammonia clearance, which includes the extrahepatic ammonia removal (muscle, brain, and kidney) was 19.6 ml/min/kg and 29.8 ml/min/kg, respectively, before and after the BAL treatment. Perifusion model shows that the ammonia clearance remaining in the body is higher than that in the BAL, and cant be effectively removed from the blood regardless of the blood flow rate. However, after the BAL treatment, the unhepatic dog had significantly lower ammonia plateau level than the controlled animal without BAL device. This might be due to the enforcement of the removal rate capacity of ammonia by the skeletal, muscle, and brain. The effective treatment using the BAL system for severe liver failure is directed toward reducing the ammonia pressure concerning skeletal muscle and brain, and enforcingdevelopment of remarkable reduction in the plateau level of ammonia in the unhepatic dog without the burden to other organs. their ammonia removal rate capacity. The BAL support may contribute to the development of remarkable reduction in the plateau level of ammonia in the unhepatic dog without the burden to other organs.
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