When an attempt is made to sustain a strong contraction in a human muscle for a period of time, the force inevitably falls. The failure to sustain the force indicates that the muscle has become fatigued. In this mechanistic approach, fatigue can be defined as the inability to maintain or continue to develop the force required to perform a particular task. However, the metabolic changes leading to loss of force presumably started at the beginning of a fatiguing contraction before the development of fatigue as we have defined it. A subject performing a fatiguing task will become progressively more aware of the effort he or she is making. Eventually, the muscle becomes painful (particularly in continuous contractions) and finally the subject is unable to maintain the force. Relaxation rapidly reverses the symptoms.

Fatigue can be local, affecting a single muscle, or generalized, after exhausting the whole body as in exercise. Presumably, the factors limiting performance are different with the two types of fatigue. Almost all studies of skeletal muscle fatigue are acute, with fatigue having developed over the period of an hour or less in a previously normal (fresh) muscle. Virtually nothing is known about chronic fatigue, i.e. a state in which the muscle has not yet recovered from previous effort. Despite our incomplete understanding, chronic fatigue of the inspiratory muscles may be common. As with skeletal muscle fatigue, respiratory muscle fatigue can be defined as an inability of the respiratory muscles to continue to develop sufficient respiratory pressure swings to maintain normal alveolar ventilation. In contrast with skeletal muscle fatigue, respiratory muscle fatigue is characterized by two unique features.

1. Because the respiratory muscles are essential for life, fatigue is life-threatening.

2. The respiratory muscles, particularly the diaphragm, are different from other skeletal muscles. Indeed, the diaphragm must contract phasically during life and thus functionally appears to have more similarities with the myocardium than with limb muscles.

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