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Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure
Author(s) -
Rose Christopher,
Michalak Adrianna,
Pannunzio Marc,
Chatauret Nicolas,
Rambaldi Andrea,
Butterworth Roger F.
Publication year - 2000
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/he.2000.5923
Subject(s) - hypothermia , microdialysis , portacaval anastomosis , medicine , cerebral edema , hepatic encephalopathy , anesthesia , encephalopathy , edema , extracellular , glutamate receptor , ischemia , extracellular fluid , endocrinology , cirrhosis , central nervous system , chemistry , biochemistry , portal hypertension , receptor
Mild hypothermia is effective in the prevention of brain edema associated with cerebral ischemia and traumatic brain injury. Brain edema is also a serious complication of acute liver failure (ALF). To assess the effectiveness of hypothermia in ALF, groups of rats were subjected to hepatic devascularization (portacaval anastomosis, followed 48 hours later by hepatic artery ligation), and body temperatures were maintained at either 35°C (hypothermic) or 37°C (normothermic). Mild hypothermia resulted in a significant delay in the onset of severe encephalopathy and in reduction of brain water content compared with normothermic ALF rats (control [n = 8] 80.22%; ALF‐37°C [n = 8] 81.74%; ALF‐35°C [n = 8] 80.48% [ P < .01 compared with ALF‐37°C]). This protective effect was accompanied by a significant reduction of cerebrospinal fluid (CSF) (but not plasma) ammonia concentrations (CSF ammonia: control: 0.05 mg/dL; ALF‐37°C: 1.01 mg/dL; ALF‐35°C: 0.07 mg/dL, P < .01 compared with ALF‐37°C). In vivo cerebral microdialysis studies revealed that mild hypothermia resulted in a significant reduction of extracellular glutamate concentrations in the brains of rats with ALF (control: 1.06 μmol/L; ALF‐37°C: 2.74 μmol/L; ALF‐35°C: 1.49 μmol/L [ P < .01 compared with ALF‐37°C]). These findings suggest that: 1) mild hypothermia is an effective approach to the prevention of the central nervous system consequences of experimental ALF; and that 2) the beneficial effect of hypothermia is mediated via mechanisms involving reduced blood‐brain transfer of ammonia and/or reduction of extracellular brain glutamate concentrations. Mild hypothermia may be an effective approach to delay the onset of brain edema in patients with ALF awaiting liver transplantation.