Prolonged mechanical ventilation (MV) results in reduced diaphragmatic maximal force production and diaphragmatic atrophy. To investigate the mechanisms responsible for MV-induced diaphragmatic atrophy, we tested the hypothesis that controlled MV results in oxidation of diaphragmatic proteins and increased diaphragmatic proteolysis due to elevated protease activity. Further, we postulated that MV would result in atrophy of all diaphragmatic muscle fiber types. Mechanically ventilated animals were anesthetized, tracheostomized, and ventilated with 21% O2 for 18 hours. MV resulted in a decrease (p < 0.05) in diaphragmatic myofibrillar protein and the cross-sectional area of all muscle fiber types (i.e., I, IIa, IId/x, and IIb). Further, MV promoted an increase (p < 0.05) in diaphragmatic protein degradation along with elevated (p < 0.05) calpain and 20S proteasome activity. Finally, MV was also associated with a rise (p < 0.05) in both protein oxidation and lipid peroxidation. These data support the hypothesis that MV is associated with atrophy of all diaphragmatic fiber types, increased diaphragmatic protease activity, and augmented diaphragmatic oxidative stress.

The aim of this study was to investigate changes in muscle function, muscle structure, and calpain activity after high-force eccentric exercise. Eleven healthy males performed 300 maximal voluntary eccentric actions with knee extensors in one leg. Maximal force-generating capacity was measured before exercise and regularly during the next 7 d. Biopsies from musculus vastus lateralis were taken in both control and exercised legs 0.5, 4, 8, 24, 96, and 168 h after exercise for evaluation of myofibrillar structure, extracellular matrix proteins, and calpain activity. In the exercised leg, peak torque was reduced by 47 +/- 5% during exercise and was still 22 +/- 5% lower than baseline 4 d after the exercise. Calpain activity was three times higher in the exercised leg compared with the control leg 30 min after exercise. Myofibrillar disruptions were observed in 36 +/- 6% of all fibers in exercised muscle and in 2 +/- 1% of fibers in control muscle. The individual reductions in peak torque correlated with the proportion of fibers with myofibrillar disruptions (r = 0.89). The increase in calpain activity was not correlated to the proportion of fibers with myofibrillar disruptions. Nevertheless, the characteristics of the myofibrillar disruptions mimicked calpain-mediated degradation of myofibrils. Tenascin-C and the N-terminal propeptide of procollagen type III showed increased staining intensity on cross-sections 4-7 d after the exercise. Myofibrillar disruptions seem to be a main cause for the long-lasting reduction in force-generating capacity after high-force eccentric exercise. The increase in calpain activity, but the lack of a relationship between calpain activity and the amount of muscle damage, suggests multiple roles of calpain in the damage and repair process.

After a standardized 6-min bicycle ergometer exercise (89% VO2max) lactic acid removal rates were compared during recovery at rest and exercies at 29.7, 45.3, 61.8, and 80.8% VO2max, and twice while the subjects (N = 7) regulated their own recovery exercise. Blood samples were taken after the standardized exercise and every 5 min during the 30-min recovery periods. During the controlled recovery periods lactic acid removal rates were dependent on the intensity of the recovery (Y‣ = 0.103 + 0.218chi - 0.464 X 10(-2)chi2 + 0.252 X 10(-4)chi3). Optimal removal was predicted to occur at 32% VO2max. Removal rates during the self-regulated recoveries were not different (P greater than 0.05), but these removal rates were faster than during recovery at rest and exercise at 61.8 and 80.8% VO2max (P less than 0.01). Removal rates during the self-regulated recovery and recovery at 29.7 and 45.3% VO2max were not different (P greater than 0.05). The subjects were therefore able to remove lactic acid effectively when selecting their own recovery exercise.