Many characteristics of skeletal muscle grafts, including mass, functional cross-sectional area, maximum tension development, and oxidative capacity, remain below control muscle values. These deficits potentially limit the usefulness of the graft to the host organism in tasks requiring strength or endurance. In addition to transplantation, the degeneration of skeletal muscle fibers occurs following a variety of diseases, trauma, and excessive physical exercise (especially if lengthening contractions occur). Regardless of the insult inducing degeneration, regeneration of muscle fibers appears to follow a common pathway. The objective is to determine the effects of the intensity and duration of chronic exercise on the structure and function of free and of vascularized skeletal muscle grafts. In free grafts, the muscle will spontaneously revascularize and muscle fibers will degenerate and new fibers will regenerate. In vascularized grafts, the fibers survive. In both grafts, the fibers show a large functional deficit compared to control muscle. Hindlimb muscles will be grafted orthotopically in rats. Chronic physical activity patterns will be changed by daily running on a motor driven treadmill an by ablation of muscles synergistic to the graft. It has been well documented in normal muscle, and there are limited data on grafts, that chronic exercise of the appropriate intensity and duration can increase variables which show a deficit in grafts relative to control values. The change of activity will start at 28 days postgrafting and grafts will be studied through 112 days. The capability of different chronic activity patterns to alter growth in grafts that differ as to fiber type and anatomical site will be investigated. Outcomes will be evaluated by morphological (gross dimensions, histochemistry), biochemical (protein concentrations, protein turnover, metabolic marker) and physiological (contractile properties) techniques. Physical exercise is a complex stimulus to skeletal muscle in terms of the type of contraction, the tension development during contraction, and the frequency, intensity and duration of exercise sessions. Resolution of these complexities will provide the scientific basis for establishing postgrafting procedures to improve the structure and function of grafts in humans and in the rehabilitation of muscles in which some fibers have regenerated due to disease, trauma or excessive exercise.
Showing the most recent 10 out of 12 publications
