Glutathione is a major antioxidant, and, in the present study, we investigated whether a clinical model of short warm ischaemia and reperfusion of the human liver during surgery would influence glutathione and amino acid metabolism. Previous studies in humans have demonstrated that ischaemia and reperfusion in skeletal muscle for up to 120 min have no major effect on muscle glutathione concentrations. Liver ischaemia and reperfusion in animals have demonstrated diverging results concerning glutathione metabolism. In the present study, six patients with liver malignancies, undergoing liver resection during warm ischaemia, were included. Liver biopsies were obtained from healthy appearing liver tissue from both lobes before ischaemia and at maximal ischaemia, and from the remaining liver lobe after 5, 10, 15, 20, 25 and 30 min of reperfusion. The biopsies were analysed for glutathione, amino acids and lactate. Median ischaemia time was 28 (range, 15–36) min. Lactate increased 266% at maximal ischaemia ( P <0.05). No alterations in glutathione concentrations or the redox status of glutathione (GSH/total glutathione) were observed. Glutamate decreased 22% ( P <0.05) at maximal ischaemia and increased thereafter 72% at 30 min of reperfusion ( P <0.05). Alanine increased 105% at maximal ischaemia ( P <0.05) and was normalized during reperfusion. BCAAs (branched-chain amino acids) increased 67% at maximal ischaemia ( P <0.05). In conclusion, short-time ischaemia and reperfusion in the human liver did not affect glutathione concentrations, whereas changes were observed in amino acid concentrations during both ischaemia and reperfusion.

The temporal pattern of metabolic alterations in muscle tissue during total ischaemia and reperfusion are not well-characterized in humans with respect to glutathione, amino acids and energy-rich compounds. In the present study, knee replacement surgery was used as a clinical model to elucidate this pattern of metabolic alterations. Patients ( n =15) undergoing elective knee replacement surgery employing tourniquet ischaemia were studied. Muscle biopsies were taken from the quadriceps femoris muscle on the operated side preoperatively, at maximal ischaemia and after 24 h of reperfusion. The biopsies were analysed for glutathione, amino acids and energy-rich compounds. In addition the patients were randomized to receive either glucose or a mannitol infusion in the 24 h following tourniquet ischaemia. During ischaemia, muscle lactate increased by 400% ( P <0.05) and phosphocreatine decreased by 70% ( P <0.05). During the subsequent 24 h of reperfusion, muscle-reduced glutathione and total glutathione decreased by 27% and 22% ( P <0.05) respectively. The muscle amino acid pattern changed during ischaemia with an increase in alanine by 65% ( P <0.001) and a decrease in glutamate by 29% ( P <0.001). During the reperfusion part of the study, no differences attributable to the infusion of mannitol or glucose were observed. During tourniquet ischaemia and subsequent reperfusion, changes in glutathione metabolism developed, indicating oxidative stress. Knee replacement surgery as a clinical model was useful during the ischaemia period, whereas the reperfusion period was dominated by the general changes seen postoperatively.

The general perception that catabolism and inflammation are associated with a high synthesis rate of total liver protein and a low albumin synthesis rate has been challenged in recent years by several studies in man, indicating that the synthesis rate of albumin in response to a catabolic insult is increased rather than decreased. Thus changes in liver protein synthesis rates in conjunction with catabolism and acute inflammation in man need to be characterized better. The aim of the present study was to measure protein synthesis rates of total liver protein and albumin during a state of acute inflammation. Patients ( n =10) undergoing acute laparoscopic cholecystectomy due to acute cholecystitis were investigated. FSRs (fractional synthesis rates) of total liver protein (liver biopsy specimens) and albumin (plasma samples) were investigated as early as possible during the surgical procedure, using a flooding dose of L -[ 2 H 5 ]phenylalanine. The results were compared with a reference group of patients without cholecystitis undergoing elective laparoscopic cholecystectomy ( n =17). FSR of total liver protein was 60% higher ( P <0.001) and the FSR of albumin was 45% higher ( P <0.01) in the cholecystitis patients compared with the control group. In conclusion, the synthesis rates of total liver protein and albumin are both increased in patients with an acute general inflammatory reaction undergoing laparoscopic cholecystectomy.