Skeletal muscle glutathione is depleted in critically ill patients

Objective: To investigate the concentrations of reduced and total glutathione in relation to the muscle free amino acid pattern in critically ill patients and matched healthy controls, Design: Prospective case control, Setting: University hospital intensive care unit (ICU), Patients: Eleven critically ill patients in the intensive care unit were studied after a stay of at least 4 days, Eleven age- and gender matched metabolically healthy patients undergoing elective surgical procedures served as controls, Interventions: None, Measurements and Main Results: Reduced and total glutathione concentrations were determined in skeletal muscle, in plasma, and in whole blood, together with muscle free amino acid concentrations, In the ICU group, reduced and total glutathione values were 57% and 62%, respectively, of the values seen in the control group (p < .001). In addition, a decreased ratio between reduced and total glutathione compared with the controls was seen (0.80 as compared with 0.91, p < .001), The glutamine concentration in skeletal muscle in the ICU group was 72% lower compared with that value seen in healthy controls (p < .001), Correlations were found between the concentrations of glutamine and the total muscle glutathione (r(2) = .46, p < .001), as well as between glutamine and the ratio of reduced and total glutathione (r(2) = .45, p < .001) in skeletal muscle, suggesting that the redox status of glutathione and the glutamine status of the tissue are related, Conclusions: Critical illness is associated with alterations in muscle glutathione metabolism. The muscle-reduced glutathione concentrations decrease and, in addition, the ratio between reduced and total glutathione decreases, indicating a situation of oxidative stress in this tissue, This decrease may impair the defense of muscle against oxygen free radicals and influence amino acid transport, thus contributing to the loss of balance between protein synthesis and protein degradation that is characteristic of protein catabolism.