Background/Aim: Brain edema is a common fatal complication in acute liver f
ailure. It is related to an acute change in brain osmolarity secondary to t
he glial accumulation of glutamine. Since high cerebral blood flow (CBF) pr
ecedes cerebral herniation in fulminant hepatic failure we first determined
if an increase in brain water and glutamine are prerequisite to a rise in
CBF in a model of ammonia-induced brain edema. Secondly, we determined if s
uch a cerebral hyperperfusion is mediated by nitric oxide synthase (NOS).
Methods: Male rats received an end-to-side portacaval anastomosis (PCA). At
24 h, they were anesthetized with ketamine and infused with ammonium aceta
te (55 muM/kg per min). Studies were performed at 60, 90, 120, 150 and 180
min after starting the ammonia infusion and once the intracranial pressure
had risen three-fold (mean 210'). Brain water (BW) was measured using the g
ravimetry method and CBF with the radioactive microsphere technique. Glutam
ine (GLN) in the CSF was sampled via a cisterna magna catheter. The neurona
l NOS was specifically inhibited by 1-2-trifluoromethylphenyl imidazole (TR
IM, 50 mg/kg intraperitoneally) and in separate studies nonspecifically by
N-omega-nitro-L-arginine (L-NNA, 2 mug/kg per min intravenously)
Results: At 90', brain water was significantly increased (P < 0.015) as com
pared to the 60' group while CBF was significantly different at 150'. A sig
nificant correlation was observed between values of CBF and brain water (r
= 0.88, n = 36, P < 0.001). Administration of either TRIM or L-NNA did not
prevent the development of cerebral hyperperfusion and edema.
Conclusion: We observed that cerebral hyperemia follows an initial rise in
brain water content, rather than in the cerebrospinal fluid concentration o
f glutamine. The rise in CBF further correlated with brain water accumulati
on and was of critical importance for the development of intracranial hyper
tension. The unique mechanism for the rise in CBF in hyperammonemia was not
prevented by NOS inhibition indicating that NO is not the mediator of high
CBF and intracranial hypertension. (C) 2001 European Association for the S
tudy of the Liver. Published by Elsevier Science B.V. All rights reserved.