METABOLITE ACCUMULATION INCREASES ADENINE-NUCLEOTIDE DEGRADATION AND DECREASES GLYCOGENOLYSIS IN ISCHEMIC RAT SKELETAL-MUSCLE

Adenine nucleotides and glycogen are degraded in skeletal muscle durin g no-flow ischaemia. Past investigations have ascribed these metabolic changes to the severe energetic stress which arises with the removal oi exogenous substrates (principally oxygen). We tested this hypothesi s by measuring the high-energy phosphagen and glycogen contents of sti mulated rat hindlimb muscles (1 twitch s(-1)) prior to and following 4 0 min of no-flow ischaemia or hypoxic perfusion without glucose (PaO2 = 4.6 +/- 0.1 torr, plasma glucose = 0.3 +/- 0.1 mmol L-1). Both exper imental protocols eliminated exogenous substrate supply, however, the maintenance of flow during hypoxic perfusion ensured the removal of me tabolic by-products. A period oi forty minutes of skeletal muscle isch aemia was characterized by reductions in the total adenine nucleotide pool, phosphocreatine and glycogen in the slow oxidative soleus, fast oxidative-glycolytic plantaris and the fast glycolytic while gastrocne mius. Compared to ischaemia, the total adenine nucleotide pool was hig her (by 7.2-13.3 mu mol g(-1) dry wt) and the glycogen content lower ( by 10.0-16.6 mu mol g(-1) dry wt) in skeletal muscle exposed to hypoxi c perfusion without glucose. The ability of hypoxic perfusion to atten uate TAN degradation and augment glycogenolysis can be attributed to m etabolic by-product removal. By limiting muscle lactate and PCO2 accum ulation, hypoxic perfusion without glucose attenuates cellular acidifi cation; this could in turn limit AMP deaminase activation and glycogen phosphorylase inhibition. We conclude that the ischaemia-induced alte rations in adenine nucleotide and glycogen metabolism arise in respons e to the elimination of exogenous substrates and to the accumulation o f metabolic by-products.