Glutamine administration during total parenteral nutrition protects liver adenosine nucleotides during and after subsequent hemorrhagic shock.

Abstract

Glutamine supplementation of total parenteral nutrition (TPN) in stressed patients has been advocated. To determine whether glutamine supplementation affects the host response to conditions of stress, animals were given TPN with or without glutamine for 7 days. They were then subjected to the acute stress of hemorrhagic shock, which results in marked loss of hepatic adenosine triphosphate (ATP) and adenosine diphosphate (ADP), with accumulation of adenosine monophosphate (AMP) and the metabolites adenosine, inosine, hypoxanthine, and xanthine. This loss of ATP and accumulation of metabolites contributes to subsequent tissue damage. The hypothesis of the study was that glutamine supplementation would significantly improve restoration of hepatic adenosine nucleotides before and after hemorrhagic shock. Sprague-Dawley rats were given TPN for 7 days. One half of the animals (n = 8) received TPN supplemented with glutamine, while one half received TPN with an isonitrogenous mixture of alanine and glycine. Animals were subjected to hemorrhagic shock for 30 minutes and then resuscitated using only heparinized shed blood. Liver biopsies were taken pre- and post-shock, and at 30 and 60 minutes after resuscitation. ATP, ADP, AMP, and their metabolites were measured using gradient high-performance liquid chromatography. After 7 days of TPN, baseline values of ATP, ADP, AMP, and metabolites were similar between the 2 groups before the initiation of shock. Glutamine-treated animals manifested a 40% decrease in ATP level immediately after shock and recovered to 90% of baseline within 60 minutes. By contrast, the control animals manifested a 66% decrease in ATP level after the shock period and recovered only to 60% of baseline at 1 hour postresuscitation. Similar changes were observed in ADP levels and were accompanied by corresponding changes in AMP and adenosine metabolites, all of which rose during shock and fell after resuscitation. Glutamine supplementation significantly protected the liver from tissue damage caused by hemorrhagic shock. ATP levels remained higher during shock and recovered more rapidly after resuscitation. Glutamine supplementation may help to protect cellular energy stores in the stressed organism and may offer opportunities for therapeutic intervention during and after stress.