The fundamental intracellular mechanisms underlying exercise intolerance and muscle weakness in patients with systemic sclerosis (SSc) are poorly understood. Thus, in 6 SSc patients (55±11 yrs) and 6 age-matched healthy controls (50±13 yrs), we assessed both skeletal muscle metabolism and intracellular O2 availability in vivo during submaximal contractions. Specifically, during dynamic plantar flexion exercise at 40% of maximal aerobic power, we used a multi-modal approach combining phosphorus and proton MRS of deoxymyoglobin, to examine both skeletal muscle energy pathways and intracellular partial pressure of O2 (iPO2). Both myoglobin O₂ levels (SSc: 70±7% and controls: 79±4%; P=0.03;) and end-exercise iPO2 (SSc: 8±4 mmHg and controls: 17±8 mmHg; P=0.021; d=1.36) were lower in SSc than healthy controls. The rate of ATP synthesis from oxidative phosphorylation was also lower in SSc than controls (SSc:5.2±3.4 mM.min-1; Controls:11.8±3.6 mM. min-1; P=0.015) whereas PCr depletion was augmented (SSc:55±15 % from resting baseline; Controls:77±9 % from resting baseline; P=0.015). This shift toward a greater reliance on anaerobic metabolism led to an accumulation of inorganic phosphate diprotonated during exercise (P=0.037). Together, these findings indicate that critically low iPO2 severely limits oxidative phosphorylation rate even during moderate-intensity dynamic plantar flexion exercise in patients with SSc. The magnitude of the disease-induced shift in metabolism and iPO2 were so extensive that they were greater than the metabolic alterations found in patients suffering from advanced chronic cardiovascular diseases. In addition, the compensatory increase in anaerobic metabolism resulted in greater metabolites accumulation, which could amplify the susceptibility to muscle fatigue in SSc patients.
Layec et al. (Thu,) studied this question.