Muscle glutathione metabolism during ischemia and reperfusion in patients undergoing aorto-bifemoral bypass surgery

After an ischemia time of 1 h during aortic aneurysm surgery, muscle glutathione redox-status is not altered, indicating that this ischemic insult is well within the scavenging capacity of muscle glutathione, the most important endogenous scavenger. In the present study, the impact of elective aorto-bifemoral bypass surgery, involving a longer ischemia time, on muscle glutathione and its redox-status was investigated.

Leg muscle biopsies were obtained pre-operatively, at maximal ischemia, after 10 min and 24 h of reperfusion from 12 patients undergoing aorto-bifemoral bypass surgery. Muscle glutathione, free amino acids and energy-rich compounds were determined.

Clamping times were 113 (99-120 min); median (quartiles). At maximal ischemia, muscle lactate increased by 7.5 (4.0-10.7) mmol/kg dry weight (dw) (P < 0.001) and phosphocreatine (PCr) decreased by 14.6 (8.9-23.3) mmol/kg dw (P < 0.001). At maximal ischemia, reduced glutathione (GSH) was unaltered but muscle glutamate decreased by 0.51 (0.30-0.85) mmol/kg wet weight (ww) (P < 0.001). At 24 h post-operatively, the reduced glutathione decreased by 0.47 (0.34-0.65) mmol/kg (ww) (P < 0.001) without changes in oxidized glutathione (GSSG) or in glutathione redox-status. Cysteine and glycine, the two other constituent amino acids to glutathione, did not change during the study period.

Ischemia of 2 h during aorto-bifemoral bypass was associated with changes in muscle energy-rich compounds but without any changes in glutathione redox-status. A decreased antioxidative capacity, as reflected by a decrease in muscle glutathione concentrations, was seen 24 h post-operatively, still without changes in glutathione redox-status. This is not different from the changes seen after abdominal surgery not involving ischemia-reperfusion.