Response To Prolonged Endurance Training and Detraining In Mitochondrial Myopathy

Abstract

Patients with mitochondrial myopathies (MM) due to mtDNA mutations in skeletal muscle often suffer disabling exercise intolerance. Our previous studies suggest that short duration (14 weeks) endurance training improves exercise capacity and increases the activity of rate-limiting enzymes. The effect of a longer duration exercise training has not been studied. PURPOSE: To assess the effect of 6 months of regular endurance training on exercise capacity and to determine if training adaptations are maintained after a prolonged period of self-selected activity in a patient with severe muscle oxidative impairment due to a mitochondrial myopathy. METHODS: A 26-year male with a heteroplasmic single large-scale deletion of mtDNA underwent 26 weeks of cycle exercise training followed by a 52 week period of self-selected activity level. Peak work, oxygen uptake (VO2), and submaximal heart rate and blood lactate were determined at baseline, after training and following 52 weeks of self-determined activity. RESULTS: Compared to baseline, training increased peak work from 110 to 130 watts and VO2 from 1.527 to 1.837 L/min. During submaximal (50 watt) exercise, peak heart rate decreased from 153 to 120 bpm and venous lactate from 6.41 to 3.25 mM. After 52 weeks of self-selected activity following 6 months of endurance training, peak work and VO2 fell to 110 watts and 1.684 L/min respectively. During submaximal exercise, after the self-selected activity period compared to post training, heart rate (133 vs. 120 bpm) and lactate levels (4.36 vs. 3.25 mM) were higher. CONCLUSION: Endurance training in MM improved work and oxidative capacity supporting the efficacy of this therapy in patients with mitochondrial myopathy due to single large-scale mtDNA deletions. Despite the substantial benefits of exercise training, the patient did not choose to maintain regular exercise training and after the 52 week period of self-selected activity, exercise capacity declined to near pre-training levels indicating that deconditioning contributes to exercise limitations in these patients and that the applicability of exercise training as therapy is limited by patient motivation.