Historical Perspective: A Framework for Interpreting Pathobiological Ideas on Human Muscle Fatigue

The flow of ideas on the causes of human muscle fatigue appear to have been established in the literature during the last century. Critical analysis had to await innovative experimental designs or techniques. Progress has come particularly from the recognition of inconsistencies, particularly in clinical conditions in which there are alterations in the supply of energy or contractile function. While there is a continuing search for a unique cause of fatigue, much evidence points to there being different causes according to the type of muscular activity or clinical condition. “Nature’s experiments” (patients exhibiting isolated defects of function or metabolism) offer unique opportunities for understanding the relative importance of particular levels of metabolic organization or physiological control. Theories of limiting biochemical processes and the Ca- kinetic basis of electromechanical coupling defects are both essentially “single-cell” models of fatigue. Functional requirements appear to determine the diversity of structure and organization of motor units. This would suggest that a “muscle cell population” approach would take into account the consequences of disease altering the number, type of functioning fibers or intrinsic strength of individual fibers. A graphical model is offered to allow a possible interpretation of the cause of fatigue in different forms of exercise and clinical conditions.