SYMPATHETIC ACTIVATION IN EXERCISE IS NOT DEPENDENT ON MUSCLE ACIDOSIS - DIRECT EVIDENCE FROM STUDIES IN METABOLIC MYOPATHIES

Muscle acidosis has been implicated as a major determinant of reflex s ympathetic activation during exercise. To test this hypothesis we stud ied sympathetic exercise responses in metabolic myopathies in which mu scle acidosis is impaired or augmented during exercise. As an index of reflex sympathetic activation to muscle, microneurographic measuremen ts of muscle sympathetic nerve activity (MSNA) were obtained, from the peroneal nerve. MSNA was measured duping static handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in patients i n whom exercise-induced muscle acidosis is absent (seven myophosphoryl ase deficient patients; MD [McArdle's disease], and one patient with m uscle phosphofructokinase deficiency [PFKD]), augmented (one patient w ith mitochondrial myopathy [MM]), or normal (five healthy controls). M uscle pH was monitored by P-31-magnetic resonance spectroscopy during handgrip exercise in the five control subjects, four MD patients, and the MM and PFKD patients. With handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute [bpm] and total activity [%]) w as not impaired in patients with MD (17+/-2 bpm, 124+/-42%) or PFKD (6 5 bpm, 307%), and was not enhanced in the MM patient (24 bpm, 131%) co mpared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia s tudied in one McArdle patient, caused sustained elevation of MSNA abov e basal suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an enhanced drop in muscle pH of 0.51 U in the MM patient co mpared with the decrease in controls of 0.13+/-0.02 U. In contrast, mu scle pH increased with exercise in MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with glycogenolytic, glycolytic, and o xidative phosphorylation defects show normal muscle sympathetic nerve responses to static exercise. These findings indicate that muscle acid osis is not a prerequisite for sympathetic activation in exercise.