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Indomethacin prevents the development of experimental ammonia‐induced brain edema in rats after portacaval anastomosis
Author(s) -
Chung Chuhan,
Gottstein Jeanne,
Blei Andres T.
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.26383
Subject(s) - portacaval anastomosis , cerebral blood flow , medicine , cisterna magna , cerebral edema , anesthesia , intracranial pressure , fulminant hepatic failure , edema , hyperammonemia , brain edema , hypothermia , cerebrospinal fluid , cirrhosis , portal hypertension , transplantation , liver transplantation
Patients with fulminant hepatic failure (FHF) die with brain edema, exhibiting an increased cerebral blood flow (CBF) at the time of cerebral swelling. Mild hypothermia prevents brain edema in experimental models and in humans with FHF, an effect associated with normalization of CBF. To study the effects of alterations of CBF on the development of brain edema, we administered intravenous (IV) indomethacin to rats receiving an ammonia infusion after portacaval anastomosis. This model predictably develops brain edema and a marked increase in CBF at 3 hours of infusion. Brain water was measured with the gravimetry technique; CBF was monitored with both laser Doppler flowmetry and radioactive microspheres, whereas intracranial pressure (ICP) was monitored with a cisterna magna catheter. Coadministration of indomethacin prevented the increase in CBF seen with ammonia alone (110 ± 19% vs. −2 ± 9%) as well as the increase in brain water (80.86 ± 0.12% vs. 80.18 ± 0.06%) and the increase in ICP. Plasma ammonia and brain glutamine levels were markedly elevated in the ammonia‐infused group and unaffected by indomethacin. However, ammonia uptake by the brain was significantly reduced by indomethacin. Levels of 6‐keto‐PGF 1α , a stable metabolite of prostacyclin, were reduced in the cerebrospinal fluid (CSF) of indomethacin‐treated animals. As with mild hypothermia, avoiding cerebral vasodilatation with indomethacin will prevent the development of brain edema in this hyperammonemic model. Cerebral vasoconstriction reduces cerebral ammonia uptake and, if selective to the brain, may be of benefit in FHF.