Knee replacement surgery as a human clinical model of the effects of ischaemia/reperfusion upon skeletal muscle
Résumé
Background: The temporal pattern of metabolic alterations in muscle tissue are not well characterised in man with respect to glutathione, amino acids and energy rich compounds during total ischemia and reperfusion. Here knee replacement surgery was used as a clinical model to elucidate this pattern. Material and methods: Patients (n=15) undergoing elective knee replacement surgery employing torniquet ischemia were studied. Muscle biopsies were taken from the quadriceps femoris muscle on the operated side preoperatively, at maximal ischemia and after 24 hours of reperfusion. The biopsies were analysed for glutathione, amino acids and energy rich compounds. In addition the patients were randomised to receive either glucose or a mannitol infusion during 24 hours following the tourniquet ischemia. Results: During ischemia an increase in muscle lactate by 400 % (p < 0.05) and a decrease in phosphocreatine by 70 % (p < 0.05) were seen. During the subsequent 24 h reperfusion, muscle reduced glutathione and total glutathione decreased by 27 % and 22 % (p< 0.05) respectively. The muscle amino acid pattern changed during ischemia with a rise 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 seen. Conclusions: During tourniquet ischemia and subsequent reperfusion, changes in glutathione metabolism indicating oxidative stress developed. Knee replacement surgery as a clinical model was useful during the ischemia period, while the reperfusion period was dominated by the general changes seen postoperatively.
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