Continuous intravenous ammonia infusion as a model for the study of hepatic encephalopathy in rabbits

Fick, T E; Schalm, Solko W.; Vlieger, M. de

doi:10.1016/0022-4804(89)90060-7

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…Acute hyperammonemia was induced by a prolonged intravenous ammonium-acetate (NH4Ac) infusion as described earlier (Fick et al, 1989). After insertion ofa Venflon cannula (diameter 0.8 mm, Viggo, Helsingborg, Sweden) into an ear vein, NHaAc was infused at a constant rate of 6 ml/hr, starting with an initial dose of 0.8 mmol/kg/hr, which was subsequently increased by 0.2 mmol/kg/hr every two hours.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Acute liver failure was induced by a two-stage liver devascularization procedure as described earlier (Fick et al, 1987;Fick et al, 1989). Under anesthesia a laparotomy was performed: a loose ligature was placed around the hepatoduodenal ligament and guided through a plastic tube through the abdominal wall to the subcutaneous layer of the left subcostal region, and a small-diameter (5 mm) side-to-side portacaval shunt was constructed.…”

Section: Animal Modelsmentioning

confidence: 99%

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Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

et al. 1993

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Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were prepared from brain cortex, hippocampus and striatum. Hepatic encephalopathy was induced by a two-stage liver devascularization procedure and acute hyperammonemia by a prolonged ammonium-acetate infusion; rabbits receiving a sodium-potassium-acetate infusion served as controls. In these animal models extracellular brain glutamate levels are known to be elevated. However no significant alterations in the number nor the affinity of the MK-801 binding sites of the NMDA receptors were found during acute liver failure and acute hyperammonemia. These findings suggest that the NMDA receptor population remains unaltered in experimental encephalopathy from acute liver failure and acute hyperammonemia, despite alterations in extracellular brain glutamate levels.KEYWORDS: hepatic encephalopathy; ammonia; glutamate receptors; NMDAreceptors; MK-801. Abbreviations used in the text: NMDA_N-methyl-D-aspar tate; NH4Ac ammoniumacetate;NaKAc sodium/potassium-acetate; AMPA amino -3 -hydroxy-5 -methylisoxazole-4-propionic acid

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Section: Animal Modelsmentioning

confidence: 99%

Section: Animal Modelsmentioning

confidence: 99%

Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

et al. 1993

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“…In addition to the above-mentioned models of hepatotoxicity, administration of ammonia directly (either PO or IV) has been used for the acute induction of HE in isolation ( Fick, Schalm & de Vlieger, 1989 ; Butterworth et al, 2009 ). These artificial models of hyperammonemia may be more appropriate as a control alongside acute or chronic models of liver injury, given the absence other features of ALF and lack of a clinical correlate.…”

Section: Survey Methodologymentioning

confidence: 99%

Preclinical models of acute liver failure: a comprehensive review

Hefler

Marfil‐Garza

Pawlick

et al. 2021

PeerJ

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Acute liver failure is marked by the rapid deterioration of liver function in a previously well patient over period of days to weeks. Though relatively rare, it is associated with high morbidity and mortality. This makes it a challenging disease to study clinically, necessitating reliance on preclinical models as means to explore pathophysiology and novel therapies. Preclinical models of acute liver failure are artificial by nature, and generally fall into one of three categories: surgical, pharmacologic or immunogenic. This article reviews preclinical models of acute liver failure and considers their relevance in modeling clinical disease.

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“…Acute hyperammonemia was induced by a prolonged intravenous ammonium acetate (NH4Ac) infusion as described earlier (23). After insertion of a Venflon cannula (diameter 0.8 mm, Viggo, Helsingborg, Sweden) into an ear vein, NH4Ac was infused at a constant rate of 6 ml/hr, starting with an initial dose of 0.8 mmol/kg/hr, which was subsequently increased by 0.2 mmol/kg/hr every two hours.…”

Section: Animal Modelsmentioning

confidence: 99%

“…Acute liver failure was induced by a two-stage liver devascularisation procedure as described earlier (22,23). Under anesthesia a laparotomy was performed: a loose ligature was placed around the hepatoduodenal ligament and guided through a plastic tube through the abdominal wall to the subcutaneous layer of the left subcostal region, and a small-diameter (5 mm) side-to-side portacaval shunt was constructed.…”

Section: Animal Modelsmentioning

confidence: 99%

Strategy for reliable prenatal detection of normal male carriers of the fragile X syndrome

et al. 1994

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In experimental hepatic encephalopathy and hyperammonemia, extracellular levels of glutamate are increased in hippocampus and cerebral cortex. It has been suggested that overstimulation of glutamate receptors causes a pathological entry of calcium into neurons via receptor-operated (NMDA-and AMPA-type) or voltage-dependent calcium channels leading to calcium overload and cell death. Neurodegeneration as a result of exposure to excitotoxins, including glutamate, can be localized and quantified using 45CAC12 autoradiography. This approach was used to study cerebral calcium accumulation in rabbits with acute liver failure and acute hyperammonemia. Acute liver failure was induced in 6 rabbits, acute hyperammonemia in 4 rabbits; 4 control rabbits received sodium-potassium-acetate. At the start of the experiment 500 IxCi 45CAC12 was given intravenously. After development of severe encephalopathy, the animals were killed by decapitation. All rabbits with acute liver failure or acute hyperammonemia developed severe encephalopathy, after 13.2±1.7 and 19.3±0.5 hours respectively (mean±SEM). Plasma ammonia levels were 425±46 and 883±21 ~mol/1, respectively (p<0.05). Control rabbits maintained normal plasma ammonia levels (13±5 txmol/1), demonstrated normal behaviour throughout the study and were sacrificed after 16 hours. 45Ca2+-autoradiograms of 40 ttm brain sections were analyzed semiquantitatively using relative optical density and computerized image analysis. As compared to background levels 45Ca was not increased in hippocampus or any other brain area of rabbits with severe encephalopathy from acute liver failure or acute hyperammonemia. This suggests that, despite increased extracellular brain glutamate levels in these conditions, glutamate neurotoxicity was not important for the development of encephalopathy in these rabbits.

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Continuous intravenous ammonia infusion as a model for the study of hepatic encephalopathy in rabbits

Cited by 9 publications

References 9 publications

Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

Preclinical models of acute liver failure: a comprehensive review

Strategy for reliable prenatal detection of normal male carriers of the fragile X syndrome

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