Neurovascular muscle transfers are used in comparatively few clinical situations largely because of a significant deficit in muscle force; the goal of this work is to determine the mechanisms responsible for this unexplained deficit. This is significant because it will permit surgeons to devise new strategies to reduce the variable outcome of these procedures and to expand the clinical utility of neurovascular muscle transfers. The working hypothesis is that, after vascularized transfer, the deficit in specific force occurs when regenerating motor axons fail to reinnervate all the fibers in a muscle.
The specific aims are to test the hypotheses that, after neurovascular transfer: 1) there is in a population of individual muscle cells that remain denervated; 2) that this population of denervated fibers explains all or part of the force deficit; and 3) that incomplete reinnervation occurs, in part, because motor unit innervation ratio can increase only up to a maximum value as a response to a reduced number of innervating motor axons. To test these hypotheses, an orthotopic neurovascular transfer of the extensor digitorum longus muscle in adult rats has been designed so that the number of axons supplied to the muscle for reinnervation can be reduced dramatically. Whole muscle force and single motor unit contractile properties are measured in each muscle 120 days after the transfer procedure. The number of motor units in each muscle is estimated from peripheral nerve histomorphometry, by using the manual incremental electromyographic method, and indirectly from motor unit force and muscle fiber histomorphometric data. Large scale computer simulations are used to evaluate the effect of sample size on estimates of innervation ratio and to examine the assumptions used in the indirect estimation of innervation ratio. Molecular markers of muscle cell denervation are identified via immunohistochemical demonstration of neural cell adhesion molecule and in situ hybridization to localize mRNA coding for the embryonic subunit of the nicotinic acetylcholine receptor. These markers are used to demonstrate directly individual muscle fibers that remain denervated after vascularized transfer. Our hypotheses will be supported if, after neurovascular muscle transfer: 1) a population of denervated fibers is demonstrated; 2) the proportion of the total muscle cross sectional area occupied by denervated fibers fully explains the specific force deficit; and 3) a maximum motor unit innervation ratio is reached as the number of axons supplied to the muscle for reinnervation is decreased.
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