Frequency-induced fatigue in electrically stimulated sheep hindlimb muscles

Functional electrical stimulation (FES) is an effective technique for restoring motor function in patients with paralysis. The early onset of muscle fatigue remains a major drawback, limiting its widespread clinical adoption. It is hypothesized that the high frequencies used in FES may be the primary factor determining muscle fatigue onset. Yet few studies have assessed the dependence of muscle fatigue on stimulation frequency. In particular, there is a need for a systematic evaluation across a continuous range of frequencies. Muscle fatigue dependence on stimulation frequency was assessed in anesthetized sheep, with the aim of modeling human musculature with physiological fidelity in the absence of potentially interfering reflexes. Following surgical muscle exposure, symmetrical 250 + 250µs biphasic pulse trains were delivered via hook wire intramuscular monopolar electrodes to either the tibialis cranialis or the extensor digitorum lateralis muscle, and isometric contraction forces were recorded. Eleven frequencies were assayed from 5 Hz to 100 Hz, with rest periods of over 10 min between trials. The extracted parameters included peak force, time to peak force, time to fatigue (defined as a 25% force drop), and the slope of force decline at fatigue. Additionally, muscle contraction ripple was assessed. Both muscles exhibited increasing fatigue with frequency, revealing three distinct frequency ranges. Fatigue rate was very slow below 15-20 Hz, gradually increased between ∼20-50 Hz, and raised sharply above 50-75 Hz reaching fatigue in a few seconds. Remarkably, fatigue rate only started to increase substantially at 10-20 Hz. Force fusion increased with stimulation frequency, with both muscles showing fused contractions from approximately 12 Hz. The minimal fatigue observed at frequencies corresponding to natural motor unit firing rates suggests that the high frequencies used in FES are a key driver of fatigue.