HepaHope Product Publications

American Society for Artificial Internal Organs (ASAIO)

June 7-9, 2007
Chicago, USA

New Combined Surgical and Ammonia Induced Canine Acute Liver Failure (ALF) Model in Bio-artificial Liver (BAL) Research

Young-Im Lee1, Yoon-Kyong Yang1, Jaeho Jung1, Delai Zhao1, Young Park1, Hyoung Yoon1, Jennifer Tam1, Chintya Ganda1, Diana Choi1, Jeff Coble1, Michael Andringa1, Hyung-Taek Lee1, Jun Park1, Charles Gropper1, Sung-Soo Park1, Robert G. Gish2, Brendan M. McGuire3, Angela Panoskaltsis-Mortari4, Scott Nyberg5, Young-Suk Lim6, Han Chu Lee6, Dong-Jin Suh6

1HepaHope Inc, 2California Pacific Medical Center, 3University of Alabama, 4University of Minnesota,
5Mayo Clinic, 6University of Ulsan

To evaluate efficacy of BAL system, extant surgical or toxin induced animal models have not satisfied reproducing ALF symptoms, especially increased intracranial pressure (IICP) in patients. NH3 is key contributor in IICP and representative toxin in ALF. We developed new combined surgical and NH3 induced ALF model. A scoring system was designed for the reproducibility of ALF model, performance evaluation of BAL and the optimal survival time for therapeutic window. We did portocaval shunt surgery followed by occlusion of hepatic artery on 15 dogs. 3 groups were applied with different occlusion duration/method and frequency/amount of NH3 injection. We developed the reliable scoring system and cutoff score was 5 (table). 4 hour occlusion with umbilical band and NH3 injection of first induction (0.25mmol/kg) and maintenance (0.1mmol/kg) for 4 times was optimal to evaluate the efficacy of BAL.

 

Parameters

+1 Point

-1 Point

Liver
Damage
NH3 (μg/dl)
T. Bil (mg/dl)
AST/ALT (IU/L)
Inorganic Phosphate
(mg/dL)
ALP (IU/L)
Lactate (mmol/L)
> 400
> 0.4
> 5000
> 9
 
> 200
> 6
-100
–
< 1000
< 5
 
<100
<4

Hepatic Encephalopathy
ICP (mmHg)
CPP (mmHg)
> 20
< 20
< 6
Active bleeding

Coagulopathy

 PT (sec) > 20 < 15