Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure.
We previously demonstrated in pigs with acute liver failure (ALF) that albumin dialysis using the molecular adsorbents recirculating system (MARS) attenuated a rise in intracranial pressure (ICP). This was independent of changes in arterial ammonia, cerebral blood flow and inflammation, allowing alternative hypotheses to be tested. The aims of the present study were to determine whether changes in cerebral extracellular ammonia, lactate, glutamine, glutamate, and energy metabolites were associated with the beneficial effects of MARS on ICP. Three randomized groups [sham, ALF (induced by portacaval anastomosis and hepatic artery ligation), and ALF+MARS] were studied over a 6-hour period with a 4-hour MARS treatment given beginning 2 hours after devascularization. Using cerebral microdialysis, the ALF-induced increase in extracellular brain ammonia, lactate, and glutamate was significantly attenuated in the ALF+MARS group as well as the increases in extracellular lactate/pyruvate and lactate/glucose ratios. The percent change in extracellular brain ammonia correlated with the percent change in ICP (r(2) = 0.511). Increases in brain lactate dehydrogenase activity and mitochondrial complex activity for complex IV were found in ALF compared with those in the sham, which was unaffected by MARS treatment. Brain oxygen consumption did not differ among the study groups.


CONCLUSIONS
The observation that brain oxygen consumption and mitochondrial complex enzyme activity changed in parallel in both ALF- and MARS-treated animals indicates that the attenuation of increased extracellular brain ammonia (and extracellular brain glutamate) in the MARS-treated animals reduces energy demand and increases supply, resulting in attenuation of increased extracellular brain lactate. The mechanism of how MARS reduces extracellular brain ammonia requires further investigation.
Rose
Christopher
C
Department of Cellular Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Ytrebø
Lars M
LM
Davies
Nathan A
NA
Sen
Sambit
S
Nedredal
Geir I
GI
Belanger
Mireille
M
Revhaug
Arthur
A
Jalan
Rajiv
R
D000641:Ammonia / Q000032:analysis*; D000818:Animals; D001923:Brain Chemistry; D004195:Disease Models, Animal; D005110:Extracellular Space; D005260:Female; D018698:Glutamic Acid / Q000032:analysis; D005973:Glutamine / Q000032:analysis; D007427:Intracranial Pressure; D019344:Lactic Acid / Q000032:analysis*; D017114:Liver Failure, Acute / Q000628:therapy*; D016060:Sorption Detoxification; D013552:Swine
D005973:Glutamine; D019344:Lactic Acid; D018698:Glutamic Acid; D000641:Ammonia