Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis

Gastroenterology. 1999 Mar;116(3):686-93. doi: 10.1016/s0016-5085(99)70191-5.


Background & aims: The pathogenesis of brain edema in fulminant hepatic failure is still unresolved. Mild hypothermia (33 degrees-35 degreesC) can ameliorate brain edema after traumatic brain injury. We evaluated mild hypothermia in a model of ammonia-induced brain edema in which accumulation of brain glutamine has been proposed as a key pathogenic factor.

Methods: After portacaval anastomosis, anesthetized rats were infused with ammonium acetate at 33 degrees, 35 degrees, and 37 degreesC or vehicle at 37 degreesC. Water and glutamine levels in the brain, cardiac output, and regional and cerebral hemodynamics were measured when intracranial pressure increased 3-4-fold (ammonia infusion at 37 degrees) and matched times (other groups).

Results: Mild hypothermia reduced ammonia-induced brain swelling and increased intracranial pressure. Brain glutamine level was not decreased by hypothermia. Brain edema was accompanied by a specific increase in cerebral blood flow and oxygen consumption, which were normal in both hypothermic groups. When the ammonia infusion was continued in hypothermic rats, plasma ammonia levels continued to increase and brain swelling eventually developed.

Conclusions: Mild hypothermia delays ammonia-induced brain edema. In this model, an increase in cerebral perfusion is required for brain edema to become manifest. Mild hypothermia could be tested for treatment of intracranial hypertension in fulminant hepatic failure.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetates / toxicity
  • Ammonia / toxicity*
  • Animals
  • Body Water / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology*
  • Brain Edema / chemically induced
  • Brain Edema / physiopathology
  • Brain Edema / therapy*
  • Cardiac Output
  • Cerebrovascular Circulation
  • Glutamine / metabolism
  • Hypothermia, Induced*
  • Intracranial Hypertension / chemically induced
  • Intracranial Hypertension / therapy
  • Intracranial Pressure
  • Male
  • Oxygen Consumption
  • Portacaval Shunt, Surgical*
  • Rats
  • Rats, Sprague-Dawley


  • Acetates
  • Glutamine
  • Ammonia
  • ammonium acetate