Sundberg CW, Bundle MW. Influence of duty cycle on the time course of muscle fatigue and the onset of neuromuscular compensation during exhaustive dynamic isolated limb exercise. Am J Physiol Regul Integr Comp Physiol 309: R51-R61, 2015. First published April 15, 2015 doi:10.1152/ajpregu.00356.2014.-We investigated the influence of altered muscle duty cycle on the performance decrements and neuromuscular responses occurring during constant-load, fatiguing bouts of knee extension exercise. We experimentally altered the durations of the muscularly inactive portion of the limb movement cycle and hypothesized that greater relative durations of inactivity within the same movement task would 1) reduce the rates and extent of muscle performance loss and 2) increase the forces necessary to trigger muscle fatigue. In each condition (duty cycle ϭ 0.6 and 0.3), male subjects [age ϭ 25.9 Ϯ 2.0 yr (SE); mass ϭ 85.4 Ϯ 2.6 kg], completed 9 -11 exhaustive bouts of two-legged knee extension exercise, at force outputs that elicited failure between 4 and 290 s. The novel duty cycle manipulation produced two primary results; first, we observed twofold differences in both the extent of muscle performance lost (DC 0.6 ϭ 761 Ϯ 35 N vs. DC0.3 ϭ 366 Ϯ 49 N) and the time course of performance loss. For example, exhaustive trials at the midpoint of these force ranges differed in duration by more than 30 s (t 0.6 ϭ 36 Ϯ 2.6 vs. t0.3 ϭ 67 Ϯ 4.3 s). Second, both the minimum forces necessary to exceed the peak aerobic capacity and initiate a reliance on anaerobic metabolism, and the forces necessary to elicit compensatory increases in electromyogram activity were 300% greater in the lower vs. higher duty cycle condition. These results indicate that the fatigue-induced compensatory behavior to recruit additional motor units is triggered by a reliance on anaerobic metabolism for ATP resynthesis and is independent of the absolute level or fraction of the maximum force produced by the muscle. muscle fatigue; neuromuscular compensation; performance-duration relationship IT HAS LONG BEEN RECOGNIZED that there is a duration-dependent relationship between the levels of muscular force and mechanical power that can be maintained in exercise performed until failure. Between exhaustive efforts that elicit failure within seconds to several minutes, the losses in muscular force and power output are exponential; however, beyond this initial period of rapid decrements, similar levels of muscular performance can be sustained for hours (19,27, 31,40,45). For example, the current human record running speed (29) is 185% faster than the speed that can be sustained for an 8-min run, yet extending the duration from several minutes to 2 h results in only an additional 8% loss in running speed (32). Thus, within the endurance portion of this relationship, performance levels are essentially sustainable, a recognition that has long been attributed to the reliance on aerobic metabolism for the ATP resynthesis necessary to support the muscular contraction. In contrast,...