A gravimetric technique to evaluate brain oedema in pigs with acute liver failure : effect of L-Ornithine Phenylacetate treatment

Abstract

Abstract Background: Intracranial hypertension is a serious complication in patients with acute liver failure (ALF) which leads to brain herniation and 30% mortality. An increase in intracranial pressure (ICP) is accompanied by an increase in brain water (cerebral oedema) in which hyperammonemia is believed to play a major role. The aim of this study was to measure the amount of brain water in different regions of the brain in pigs with ALF treated with and without an ammonia-lowering compound, L-ornithine phenylacetate (OP).

Methods: 24 Norwegian Landrace pigs were used in this study. ALF was induced by hepatic devascularisation (portacaval anastomosis + hepatic artery ligation) and followed by either treatment with OP (ALF+OP) or saline (ALF). A sham operated control group was included. Animal were sacrificed after 8 hours of ALF, the brain was removed and dissected into 3 white matter and 3 grey matter regions. A sensitive gravimetric technique using gradient columns of specific gravity was used for measuring brain water.

Results: A significant increase in brain water was found in all three grey matter regions (frontal and cerebellar cortex and thalamus) in pigs with ALF vs SHAM (p<0.05). ALF pigs treated with OP demonstrated a significant decrease in brain water in the frontal and cerebellar cortex vs ALF (p<0.05). A significant increase was found in frontal white matter and brainstem in ALF vs SHAM (p<0.05). No change was found in cerebellar white matter. OP-treatment resulted in a significant lowering of brain water in frontal white matter and brainstem vs saline-treated ALF pigs (p<0.05)

Conclusion: ALF causes an increase in brain water content in 5/6 brain regions compared to SHAM demonstrating the brain does not swell homogeneously. OP-treatment attenuated ALF-induced brain water content in 4/5 regions demonstrating an association between brain oedema and hyperammonemia in those regions.