Impaired monoamine oxidase activity in dogs with portacaval shunt

Abstract

In dogs with portacaval shunt, hypertyraminemia could result from either impaired degradation by monoamine oxidase (MAO) and/or from failure of tyramine to reach this enzyme. MAO activity was evaluated in liver obtained from dogs before and after the construction of an end-to-side portacaval shunt. Diversion of portal blood from the liver by a portacaval shunt resulted in a significant (P < 0.05) decrease in hepatic MAO activity [11.9 ± 4.1 nmoles of 4-hydroxyphenylacetic acid (PHA) formed · (mg protein) −1 · hr −1] as compared to controls [28.7 ± 6.3 nmoles PHA formed · (mg protein) −1 · hr −1]. Activity was maximally reduced in shunted dogs with stages II and III hepatic encephalopathy. In addition, more than a 50 per cent reduction in both the V max and the K m of hepatic MAO for tyramine was noted in shunted dogs as compared to controls. Similar kinetic abnormalities [post-shunt, K m 52.63 ± 14.3, V max 3.8 ± 1.2 vs sham group, K m 120.1 ± 22.3 μM tyramine, V max 14.3 ± 4.5 nmoles PHA · (mg protein) −1 · hr −1], as well as decreased MAO activity [post-shunt, 1.85 ± 0.83 vs sham group, 6.7 ± 2.1 nmoles PHA formed · (mg protein) −1· hr −1], were found in cerebral cortex from encephalopathic dogs with portacaval shunt. In summary, defective MAO activity may contribute to many of the pathophysiologic events observed in dogs with portacaval anastomosis. Such abnormalities could explain the hypertyraminemia and encephalopathy that have been reported in patients and experimental animals with liver disease.