CALF MUSCLE MITOCHONDRIAL AND GLYCOGENOLYTIC ATP SYNTHESIS IN PATIENTS WITH CLAUDICATION DUE TO PERIPHERAL VASCULAR-DISEASE ANALYZED USING P-31 MAGNETIC-RESONANCE SPECTROSCOPY

1. We set out to define abnormalities of oxidative ATP synthesis, cell ular proton efflux and the efficiency of ATP usage in gastrocnemius mu scle of patients with claudication due to peripheral vascular disease, using data obtained by P-31 magnetic resonance spectroscopy during ae robic exercise and recovery. 2. Eleven patients with moderate claudica tion were studied and results were compared with 25 age-matched contro l subjects. Changes in pH and phosphocreatine concentration during rec overy were used to calculate the maximum rate of oxidative ATP synthes is (Q(max).) and the capacity of net proton efflux. Changes in pH and phosphocreatine concentration were used to estimate rates of non-oxida tive and (indirectly) oxidative ATP synthesis throughout exercise, tak ing account of abnormalities in proton efflux during exercise. 3. In p atients with claudication, slow post-exercise phosphocreatine recovery showed a 42+/-9% decrease in Q(max.), and the slow ADP recovery was c onsistent with this, pH recovery was slow, showing a 77+/-9% decrease in the capacity for proton efflux. Both abnormalities are compatible w ith a substantial reduction in muscle blood flow. 4. During exercise, increased phosphocreatine depletion and intracellular acidification we re a consequence of impaired oxidative ATP synthesis and the consequen t increase in non-oxidative ATP synthesis, compounded by reduced proto n 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 flo w. 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 hig h for given power output as in control muscle. Some of this is probabl y due to a localized loss of muscle fibres, but the rest appears to re flect reduced metabolic efficiency of the muscle. This is not a direct consequence of reduced blood flow, and may be related to change in mu scle fibre type.