STUDIES ON THE REGENERATIVE RECOVERY OF LONG-TERM DENERVATED MUSCLE IN RATS

Denervated extensor digitorum longus (EDL) muscles in rats rapidly los e mass and contractile force. After two months of denervation, mass an d maximum tetanic force have fallen to 31% and 2% of the values of con tralateral control muscles. Our purpose was to determine if grafting a long-term denervated muscle into an innervated site provides an effec tive means of restoring its structure and function. EDL muscles that h ad been denervated for periods of 2-12 months were freely grafted into innervated sites of EDL muscles in 4-month inbred host animals. Contr alateral normally innervated EDL muscles from the same donors were imp lanted into the opposite legs of the same hosts. Two months after graf ting, the muscles were removed and measurements were made in vitro of isometric contractile properties. The grafts were then prepared for mo rphological analysis. Ln all cases, the maximum forces generated by in nervated grafts of denervated muscles were greater than those generate d by denervated muscles. However, when compared with grafts of control muscles in the contralateral limb, grafts of previously denervated mu scles showed a steady decline in structural and functional recovery co rresponding to the time of previous denervation. The decline was espec ially pronounced for muscles denervated between 2 and 7 months prior t o grafting. Grafts of 7-month denervated muscles were restored to only 17% of the maximum tetanic force of contralateral control grafts comp ared with 83% for grafts of 2-month denervated muscles. The longer a m uscle had been denervated prior to grafting, the higher proportion of thin atrophic muscle fibers it contained. We conclude that grafting in to an innervated site improves the mass and maximum force of a muscle over the denervated state, but the longer the period of prior denervat ion the poorer the recovery of the grafted muscles.