N-ACETYLCYSTEINE INHIBITS MUSCLE FATIGUE IN HUMANS

N-acetylcysteine (NAC) is a nonspecific antioxidant that selectively i nhibits acute fatigue of rodent skeletal muscle stimulated at low (but not high) tetanic frequencies and that decreases contractile function of unfatigued muscle in a dose-dependent manner. The present experime nts test the hypothesis that NAC pretreatment can inhibit acute muscul ar fatigue in humans. Healthy volunteers were studied on two occasions each. Subjects were pretreated with NAC 150 mg/kg or 5% dextrose in w ater by intravenous infusion. The subject then sat in a chair with sur face electrodes positioned over the motor point of tibialis anterior, an ankle dorsiflexor of mixed-fiber composition. The muscle was stimul ated to contract electrically (40-55 mA, 0.2-ms pulses) and force prod uction was measured. Function of the unfatigued muscle was assessed by measuring the forces produced during maximal voluntary contractions ( MVC) of ankle dorsiflexor muscle groups and during electrical stimulat ion of tibialis anterior at 1, 10, 20, 40, 80, and 120 Hz (protocol 1) . Fatigue was produced using repetitive tetanic stimulations at 10 Hz (protocol 1) or 40 Hz (protocol 2); intermittent stimulations subseque ntly were used to monitor recovery from fatigue. The contralateral leg then was studied using the same protocol. Pretreatment with NAC did n ot alter the function of unfatigued muscle; MVC performance and the fo rce-frequency relationship of tibialis anterior were unchanged. During fatiguing contractions stimulated at 10 Hz, NAC increased force outpu t by similar to 15% (P < 0.0001), an effect that was evident after 3 m in of repetitive contraction (P < 0.0125) and persisted throughout the 30-min protocol. NAC had no effect on fatigue induced using 40 Hz sti muli or on recovery from fatigue. N-acetylcysteine pretreatment can im prove performance of human limb muscle during fatiguing exercise, sugg esting that oxidative stress plays a causal role in the fatigue proces s and identifying antioxidant therapy as a novel intervention that may be useful clinically.