Calf muscle mitochondrial and glycogenolytic ATP synthesis in patients with claudication due to peripheral vascular disease analysed using 31P magnetic resonance spectroscopy.

1. We set out to define abnormalities of oxidative ATP synthesis, cellular proton efflux and the efficiency of ATP usage in gastrocnemius muscle of patients with claudication due to peripheral vascular disease, using data obtained by 31P magnetic resonance spectroscopy during aerobic exercise and recovery. 2. Eleven patients with moderate claudication were studied and results were compared with 25 age-matched control subjects. Changes in pH and phosphocreatine concentration during recovery were used to calculate the maximum rate of oxidative ATP synthesis (Qmax.) and the capacity of net proton efflux. Changes in pH and phosphocreatine concentration were used to estimate rates of non-oxidative and (indirectly) oxidative ATP synthesis throughout exercise, taking account of abnormalities in proton efflux during exercise. 3. In patients with claudication, slow post-exercise phosphocreatine recovery showed a 42 +/- 9% decrease in Qmax., and the slow ADP recovery was consistent with this. pH recovery was slow, showing a 77 +/- 9% decrease in the capacity for proton efflux. Both abnormalities are compatible with a substantial reduction in muscle blood flow. 4. During exercise, increased phosphocreatine depletion and intracellular acidification were a consequence of impaired oxidative ATP synthesis and the consequent increase in non-oxidative ATP synthesis, compounded by reduced proton efflux. The acidification prevented an increase in ADP concentration which could otherwise partially compensate for the oxidative defect. All these abnormalities are compatible with a reduced muscle blood flow. 5. In addition, initial-exercise changes in pH and phosphocreatine concentration implied a 44 +/- 5% reduction in 'effective muscle mass', necessitating an ATP turnover (per litre of muscle water) twice as high for given power output as in control muscle. Some of this is probably due to a localized loss of muscle fibres, but the rest appears to reflect reduced metabolic efficiency of the muscle. This is not a direct consequence of reduced blood flow, and may be related to change in muscle fibre type.