Fatigue of hand and forearm muscle groups can limit task performance by astronauts wearing space suits. Countermeasures to delay fatigue would therefore be useful to the space program. N-acetylcysteine (NAC) has been shown to inhibit fatigue during other tasks so we tested its effects during handgrip exercise. Volunteers practiced isometric handgrip maneuvers until performance was reproducible over three successive sessions (baseline). Performance then was retested after ingesting NAC (150 mg.kg(-1)) or saline. Drug administration increased NAC and cysteine blood levels (P < 0.001). Performance of sustained maximal efforts was unaffected. During repetitive submaximal efforts, NAC delayed fatigue (130% baseline) and inhibited glutathione oxidation. Saline did not alter glutathione status or performance of sustained maneuvers; repetitive task performance was increased by 15% (P < 0.05), a placebo effect. These data indicate that NAC supports glutathione homeostasis in exercising humans and may delay muscle fatigue during repetitive handgrip exercise. Our findings support oxidative stress as a causal factor in human muscle fatigue and argue for larger translational studies to define NAC effects on human performance.

inhibitor concentrate prevents atrophy, weakness, and oxidative stress in soleus muscle of hindlimb-unloaded mice.

-Diet-induced undernutrition causes deleterious changes in the structure and function of the diaphragm muscle. Diseases associated with somatic washing cause atrophy of the respiratory muscles. In cachectic subjects, the diaphragm muscle mass and thickness are reduced in proportion to the reduction in body weight. In

Some of the common complications of acute necrotizing pancreatitis also involve pulmonary complications. These manifestations are often associated with a cephalad diaphragmatic shift. We hypothized that diaphragmatic function might be directly compromised by the acute abdominal process. This hypothesis was tested on an acute necrotizing pancreatitis (ANP) rat model. We assessed the diaphragm and peripheral (Extensor Digitorum Longus and Soleus) muscle properties in vitro using strips in control (C) and ANP animals. Contractile parameters included single twitch and a force-frequency curve (10 to 100 Hz), and an endurance capacity index (T50%) was calculated after a repetitive stimulation (30 Hz). Breathing pattern was not different between control and ANP animals, and muscular histologic examination was normal. However, ANP was associated with a marked decrease in diaphragmatic strength for all frequencies of stimulation when compared with C. Endurance capacity was also reduced in ANP animals as assessed by a lower T50% (ANP: 31 +/- 10.5 s; C: 49 +/- 10.3 s; p < 0.05). By contrast, no significant change in peripheral muscle function was observed in both groups. We conclude that ANP causes impairment in diaphragmatic strength and endurance capacity, whereas peripheral muscles are spared. These findings suggest that alterations in the respiratory pump may be involved in the genesis of acute respiratory failure in ANP.

Acute pancreatitis induced marked diaphragmatic dysfunction. Although the precise mechanisms responsible for this alteration are not precisely determined, diaphragmatic dysfunction may play a role in pancreatitis-associated respiratory failure.