TY - JOUR
T1 - Cerebral blood flow and metabolism in chronically hyperammonemic rats
T2 - Effect of an acute ammonia challenge
AU - Gjedde, Albert
AU - Lockwood, Alan H.
AU - Duffy, Thomas E.
AU - Plum, Fred
PY - 1978/4
Y1 - 1978/4
N2 - The effects of chronic hyperammonemia on cerebral metabolism were studied in rats four and eight weeks after the construction of a portacaval shunt. Compared to sham‐operated controls, shunted animals had increased arterial concentrations of ammonia and glutamine and decreased glutamate. Cerebral blood flow, measured by xenon 133 washout in animals lightly anesthetized with nitrous oxide, increased from a control of 91 ± 5 (mean ± SEM) to 139 ± 20 ml per 100 gm tissue per minute after shunting for eight weeks; however, the cerebral metabolic rate for oxygen was not different from control four or eight weeks after the shunting procedure. Following intraperitoneal administration of a small ammonium acetate load (2.6 mmol/kg), eight‐week portacaval animals consistently underwent a fall in cerebral blood flow and cerebral oxygen consumption and developed high‐voltage slow waves in the electroencephalogram. Glutamine was produced by the brains of all groups of animals; the cerebral metabolic rate for glutamine was greater than control in eight‐week portacaval rats, the only animals to show a net uptake of ammonia, along with nonspecific effects of chronic portal‐systemic shunting, may lead to uncoupling of cerebral blood flow and oxidative metabolism.
AB - The effects of chronic hyperammonemia on cerebral metabolism were studied in rats four and eight weeks after the construction of a portacaval shunt. Compared to sham‐operated controls, shunted animals had increased arterial concentrations of ammonia and glutamine and decreased glutamate. Cerebral blood flow, measured by xenon 133 washout in animals lightly anesthetized with nitrous oxide, increased from a control of 91 ± 5 (mean ± SEM) to 139 ± 20 ml per 100 gm tissue per minute after shunting for eight weeks; however, the cerebral metabolic rate for oxygen was not different from control four or eight weeks after the shunting procedure. Following intraperitoneal administration of a small ammonium acetate load (2.6 mmol/kg), eight‐week portacaval animals consistently underwent a fall in cerebral blood flow and cerebral oxygen consumption and developed high‐voltage slow waves in the electroencephalogram. Glutamine was produced by the brains of all groups of animals; the cerebral metabolic rate for glutamine was greater than control in eight‐week portacaval rats, the only animals to show a net uptake of ammonia, along with nonspecific effects of chronic portal‐systemic shunting, may lead to uncoupling of cerebral blood flow and oxidative metabolism.
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U2 - 10.1002/ana.410030409
DO - 10.1002/ana.410030409
M3 - Article
C2 - 666274
AN - SCOPUS:0017954946
SN - 0364-5134
VL - 3
SP - 325
EP - 330
JO - Annals of neurology
JF - Annals of neurology
IS - 4
ER -