Electrical stimulation of denervated EDL muscles of rats: Maintenance of mass, contractile properties and recovery following grafting.

Denervated skeletal muscles lack contractile activity and subsequently lose mass and the ability to generate force. Prolonged periods of denervation prior to reinnervation limit the potential for restoration of motor function. With normal aging, skeletal muscles of old animals have decreased mass and maximum force, and increased number of denervated muscle fibers. In adult and old rats, this study investigated the effects of electrical stimulation on denervated extensor digitorum longus (EDL) muscles. The working hypothesis was that contractile activity generated in denervated muscles by an optimum protocol of electrical stimulation maintains mass, contractility, morphology and molecular expression not different from those for control muscles, and maintains the capacity of muscles to recover mass and maximum force following grafting at levels not different from those of grafts of control muscles. A programmable, implantable stimulation system was developed. After each rat was anesthetized, the muscle was denervated by high sciatic nerve resection and a stimulator was implanted. EDL muscles were evaluated following 1 to 7 months of stimulation. Muscles from the unoperated contralateral legs served as controls. The protocol was optimized to maintain muscle mass and maximum force. Maximum force, excitability and average muscle fiber cross sectional area of stimulated-denervated muscles were maintained at higher values than reported previously. Through 4 months of stimulation-denervation, muscle mass, specific force, time-to-peak tension, half-relaxation time and excitability were maintained at values not different from values for control muscles. The upregulation of mRNA expression for MyoD, myogenin and alpha subunits of acetylcholine receptors in denervated muscles was suppressed by electrical stimulation, as reported by others. In addition, this study demonstrated different levels of suppression with different protocols of stimulation. In old rats during a two month period, when age-related declines in muscle mass and force are known to occur, stimulation of denervated muscles suppressed these declines relative to age-matched controls of innervated muscles. Despite these positive findings, for denervated muscles the recovery of mass and force following nerve-implant grafting was not improved by stimulation during the period of denervation.Ph.D.Applied SciencesBiological SciencesBiomedical engineeringBiophysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/123156/2/3068851.pd