Commentary to Accompany
Skeletal muscle fatigue constitutes a keystone concept in physiology and medicine at the core of human endeavor, quality of life and our survival, as noted in the article by Grassi and colleagues (3) in this issue of the Journal. The elite athlete coordinates superior cardiovascular, metabolic, and biomechanical capabilities to stave off fatigue and achieve superb feats of performance. At the other end of the spectrum, enhanced fatigability is pathognomonic of pathologies such as heart failure, diabetes, and pulmonary and vascular occlusive diseases. Exercise tolerance and the capacity to delay fatigue are improved by exercise training and enhanced O2 delivery.
Resolving the mechanistic bases of fatigue is absolutely central to advancing our understanding of physiological and metabolic control processes and fulfilling the National Institutes of Health mandate to relieve the burden of human suffering. However, this endeavor is complicated by the multivariate definitions of fatigue, its task/intensity/condition specificity, and simultaneous participation of multiple intramuscular and central mechanisms. Bergström and colleagues’ (2) pioneering work used muscle biopsies to demonstrate that, during prolonged heavy constant-load exercise, fatigue occurred concomitantly with muscle [glycogen] depletion. Exercise and dietary strategies that lowered or raised preexercise muscle [glycogen] caused commensurate alterations in time to fatigue. Since then, the plethora of intramuscular and extramuscular fatigue mediators proposed includes increased inorganic phosphate, hydrogen ions, reactive O2 species, temperature, decreased calcium regulation, [creatine phosphate] sodium/potassium pump function, and blood [glucose], as well as altered central motor drive, sympathetic nervous system function, and endocrine control.
Grassi et al. (3) define fatigue as a reduction in muscle force or power for a given muscle activation and exploit the commanding role of O2 delivery (and O2 consumption, V˙O2) on exercise tolerance (1,5). Notably, they emplace their consideration of fatigue within the Critical Power (critical velocity) concept (Figure). This is a crucial perspective because above critical power, skeletal muscle metabolic homeostasis cannot be maintained and time to exhaustion is predictable from W′ (anaerobic work capacity) and the power sustained relative to critical power. Specifically, for all exercise above critical power, pulmonary and muscle V˙O2 increases to V˙O2max (via V˙O2 slow component, decreased muscle efficiency). Muscle [creatine phosphate] decreases and [adenosine diphosphatefree], [inosine and adenosine monophosphate], [potassium], [H+] and blood/muscle [lactate] all increase inexorably to fatigue/exhaustion (4,6), driving the free energy change of ATP hydrolysis downward. Under these circumstances, fatigue/exhaustion does not necessarily occur concomitantly with the achievement of V˙O2max but rather depletion of W′. Grassi and colleagues (3) draw on an eclectic range of animal and human models to illuminate the compelling relationship between the V˙O2 profile, muscle energetics, and the fatigue process(es) above critical power.
For many years, the V˙O2 slow component was ignored tacitly because it simply did not fit with muscle energetics models (4). Grassi et al.’s linking V˙O2 inextricably with fatigue is a bold and timely move that promises to yield novel insights into the mechanistic bases for fatigue.
David C. Poole
Thomas J. Barstow
Departments of Kinesiology
Anatomy and Physiology
Kansas State University
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