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 35ЊC (hypothermic) or 37ЊC (normothermic). A major cause of death in patients with acute liver failure (ALF) is brain herniation resulting from raised intracranial pressure caused by a progressive increase in brain water content. 1 It has been estimated that up to 40% of patients with ALF die while on the waiting list for liver transplantation, 2 in whom, in almost all cases, death results from brain herniation. Despite several decades of investigation, the pathophysiological mechanisms responsible for the central nervous system consequences of ALF have not been fully elucidated. However, ammonia remains a prime candidate. Hyperammonemia is a consistent finding in experimental animal models of ALF resulting from hepatectomy, 3 hepatic devascularization, 4,5 or toxic liver injury 6 , and, in these cases, brain edema is invariably observed. In ALF, brain ammonia may reach millimolar concentrations, 7 and exposure of various in vitro brain preparations to millimolar concentrations of ammonia results in significant cell swelling. 8,9 Hyperammonemia is a feature of Reye' s Syndrome 10 and congenital urea cycle enzymopathies, 11 conditions in which cerebral edema is also consistently observed.Previous studies showed that hypothermia extended the survival time and prevented the development of brain edema in rats with ALF. 12 Furthermore, mild hypothermia (33°C-35°C) has been shown to be neuroprotective in experimental models of traumatic 13 and ischemic brain injury. 14 In the case of the latter, it was suggested that the beneficial effects of hypothermia were the result of inhibition of the release of neurotransmitters, rather than of an effect on cerebral energy metabolism. 15 The goals of the present investigation, therefore, were to study the effect of hypothermia on the development of hepatic encephalopathy and brain edema in relation to blood and cerebrospinal fluid (CSF) ammonia levels, and to extracellular glutamate and glutamine concentrations in rats with ALF caused by hepatic devascularization.
MATERIALS AND METHODSO-phthaldialaldehyde reagent solution, 2-mercaptoethanol, Trisacetate, Ringer' s solution constituents, and amino acid standards were purchased from Sigma Chemical Co. (St. Louis, MO). Sodium phosphate (monobasic), methanol (high-performance liquid chromatography [HPLC]-grade), and tetrahydrofuran (HPLC-grade) were obtained from Anachemia (Montreal, Quebec, Canada). Doubledistilled deionized water was used for preparation of standard amino acid solutions and buffers. The mobile phase used for HPLC was filtered through 0.45-mm-pore-size membrane filters (Millipore Corp., B...
