Standard whole skeletal muscle grafts up to 6 g in mass revascularize and reinnervate spontaneously. The revascularization follows the period of ischemia and during this period fibers degenerate and regenerate. Grafts larger than 6 g can only be grafted successfully if blood vessels are anastomosed. Compared to control muscles, all types of grafts show deficits. The most critical functional deficits observed for grafts are in maximum tetanic tension development ad resistance to fatigue. Deficits in maximum tetanic tension development for whole grafts result from regeneration of fewer fibers, or fibers with smaller cross-sectional areas. Increased fatigability of grafts is associated with decreased oxidative capacity and capillary density, and an inappropriate blood flow. In grafts, the number of fibers that regenerate is dependent on the degree of revascularization and reinnervation whereas the fiber area and types of fibers that regenerate are dependent on innervation and subsequent use. The overall goals is to compare in rabbits the functional deficits that occur in nerve-anastomosed standard and vascularized grafts transplanted into the site of the rectus femoris muscle when both types of grafts are initially equal in mass. Comparisons will be made after the maximum tetanic tension of each type of graft has stabilized. The specific aims are to determine the causes of these deficits and design procedures to reduce the deficits. Portions of latissimus dorsi muscles 1, 4, 7, and 10 g in mass, but of equal length will be grafted. Vascularization of grafts will be varied by operative procedures that result in spontaneous revascularization (standard grafts) or reperfusion of grafts by vascular anastomoses (vascularized grafts). Postoperative procedures will include ablation of synergistic muscles and contractions of grafts with chronic 10 Hz stimulation for 8\hrs. per day. With control muscles and 100 mg grafts in rats, ablation of synergists results in increased maximum tension and chronic stimulation in increased oxidative capacity, capillarity, blood flow, and resistance to fatigue. The causes of functional deficits will be evaluated by histological, histochemical, biochemical, and physiological measurements of whole grafts and of single motor units in grafts. Blood flow will be assessed by intravital microscopy and radioactive microsphere techniques. The results should clarify the optimal operative and postoperative procedures for the effective transplantation of human skeletal muscles.
NIH ExPorter
NIH ExPorter