The studies included in this dissertation address the role of blood flow and cellular oxygenation in skeletal muscle fatigue, with an underlying interest in age-related differences in muscle fatigue. In the first study, I found that blood flow immediately post-contraction was tightly coupled to contraction intensity throughout an incremental isometric dorsiflexor contraction protocol in healthy young men. This relationship was independent of fatigue, and the onset of fatigue occurred before any reduction or plateau in blood flow. These data suggest that fatigue during intermittent incremental contractions does not result from a blood flow limitation. The second study used magnetic resonance spectroscopy of deoxymyoglobin to examine the role of intracellular oxygenation in muscle fatigue during slow and rapid incremental contractions in healthy young men and women. Data from this study showed that the rate of deoxygenation relative to force during contractions was predictive of fatigue, and this was true for slow and rapid contractions. Further, intracellular oxygenation was lower, and fatigue greater, during more metabolically demanding rapid contractions. These data support a role for intracellular oxygenation in the development of fatigue. The final study investigated whether differences in intracellular oxygenation could explain age-related differences in muscle fatigue. During slow contractions, intracellular oxygenation was higher, but fatigue lower, in older compared to young subjects. After matching a subset of subjects by muscle strength, age-group differences in oxygenation were eliminated, but fatigue was still less in older subjects, suggesting that while differences in oxygenation exist between young and older subjects, they cannot explain the age-group differences in fatigue. This conclusion was supported by a similar oxygenation, but greater fatigue, in young compared to older subjects during rapid contractions. Based on these findings, intracellular oxygenation does not appear to play a role in the age-related differences in fatigue observed in this and other studies. Together, data from this dissertation suggest that intracellular oxygenation plays a role in the development of muscle fatigue, despite the ability of blood flow to match contraction intensity. Differences in oxygenation, however, cannot explain age-related differences in muscle fatigue.

Eccentric muscle contractions induce ultrastructural disruption, prolonged loss of maximal strength (MVC) and range of motion (ROM), increase in muscle soreness (SOR) and muscle proteins, and secondary damage by inflammation. The overall purpose of this dissertation research was to further examine the relationship between blood glutathione (GSH) levels and the blood creatine kinase (CK) response to eccentric exercise, and the inflammatory response, specifically neutrophil function. Study I examined the effect of resting GSH levels on CK activity after eccentric muscle contractions, and Study II examined the effect of α-lipoic acid (LA) supplementation on resting GSH levels in plasma. Study III examined the effect of eccentric muscle contractions on neutrophil function by examining gene expression of neutrophils after eccentric muscle contractions to determine which genes are up-regulated or down-regulated during initiation of inflammation. It was concluded from Study I that subjects in the low GSH group experienced less muscle damage than subjects in the high GSH group, and these changes for the low GSH group were consistent with less secondary damage due to inflammation. Study II concluded that LA supplementation for 4 weeks may not be enough to increase GSH levels in low GSH group. Study III concluded that neutrophils initiate several processes including inflammation, cytoskeletal regulation, transcription, and metabolism in response to eccentric muscle contractions with the evidence of up- or down-regulation of genes.

Studies in adults have shown that the role of the postural system during most motor behaviors is more complex than just merely minimizing positional deviations away from a stable equilibrium point. Rather, the postural system appears to be highly coordinated and integrated with other suprapostural behaviors. How the integration and coordination between the postural system and other suprapostural behaviors develops has not been extensively examined. In this project the developmental integration and coordination between posture and manual control was studied in children (7- and 10-years of age) and compared with healthy college aged adults. All subjects were required to fit a block through an opening as precision, postural and visual constraints were manipulated. Trunk and arm kinematics and center of pressure data were obtained. Compared to adults children adopt different postural strategies during the fitting task (Chapter 4), appear less able to modulate postural stability as precision demands increase (Chapter 5), and exhibit less ability to use functionally exploit postural fluctuations (Chapter 6). Taken together, results suggest that even by 10-years of age, the postural system is not integrated with the manual control system at adult like levels.

The primary aim of this dissertation was to examine the role of short-term immobilization on muscle function recovery, excitability of the muscle, evoked contractile properties of the muscle, and muscle proteins in the blood after contraction-induced muscle injury. In Studies I and II, the effects of four days of immobilization on recovery of muscle function and serum creatine kinase (CK) activity after eccentric exercise was examined in 26 males, who were placed into one of three groups: immobilization, control, or light exercise. When the damaged elbow flexor muscles were immobilized or exercised for four consecutive days, force recovery over eight days was significantly enhanced compared to a control. In Study II, during the four-day treatment period after eccentric exercise, immobilization resulted in a significant blunting of the CK response compared to the light exercise or control groups. However, increasing activity with light exercise did not have any effect on the CK response compared to control. The data from Study II suggested that reduced lymphatic transport with decreased muscular activity may have contributed to the lower CK response in the immobilized muscle. In Study III, mechanisms to explain the observations in Studies I and II with immobilization were undertaken. Muscle excitability and evoked contractile properties of the muscle were examined to determine whether immobilization altered the mechanical properties of the muscle to favor an enhanced force response. After eccentric exercise, there were immediate and prolonged reductions in the evoked contractile properties of the muscle. Immobilization, however, had no effect on these measures. CK and myoglobin were assessed during the four-day treatment period as well as during the five-day recovery period. There was a significant difference in the CK response between groups, with the immobilization demonstrating significant blunting of the CK response during the treatment period. Upon remobilization of the arm, CK activity increased but not as high as was anticipated. The myoglobin response, however, was not different between groups. Because their routes of entry into the blood differ, taken together, the myoglobin and CK response suggest that lymph transport likely contributed to the blunting of the CK response observed with immobilization.