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Chronic inhibition of brain protein synthesis after portacaval shunting

A possible pathogenic mechanism in chronic hepatic encephalopathy in the rat

Departments of Neurology, Cornell University Medical College, New York, New York, and the University of California at Los Angeles.

We investigated the effects of chronic portacaval shunting, with or without additional ammonia loading, on brain protein synthesis in unanesthetized rats by continuous intravenous infustion of ³H-lysine (10 µmoles per gram, 0.2 µCi/µmole). Lysine was incorporated into forebrain proteins at a rate of 1.6 nanomoles/mg protein per hour in sham-operated controls, but at a rate of only 0.83 nanomoles/mg protein per hour (p < 0.001) in paired rats 6 to 8 weeks after construction of a portacaval shunt. An acute load of ammonium acetate in portacaval-shunted animals further decreased the rate of lysine incorporation into forebrain proteins. Chronic inhibition of protein synthesis may play a role in the pathogenesis of chronic portacaval encephalopathy.

Reprint requests should be addressed to Dr. Wasterlain, Neurology Division, UCLA San Fernando Valley Medical Program, VA Hospital, 16111 Plummer Street, Sepulveda, CA 91343.

Presented in part at the twenty-eighth annual meeting of the American Academy of Neurology, Toronto, April 1976.

This study was supported by Research Grant NS-13227from the NINCDS and by the Research Service of the Veterans Administration. Dr. Wasterlain is a recipient of Research Career Development Award NS-703634, and Dr. Lockwood is a recipient of NINCDS Research Fellowship NS-02149.

Accepted for publication May 16, 1977.