Studies on the regenerative recovery of long-term denervated muscle in rats

Denervated extensor digitorum longus (EDL) muscles in rats rapidly lose mass and contractile force. After two months of denervation, mass and maximum tetanic force have fallen to 31% and 2% of the values of contralateral control muscles. Our purpose was to determine if grafting a long-term denervated muscle into an innervated site provides an effective means of restoring its structure and function. EDL muscles that had been denervated for periods of 2-12 months were freely grafted into innervated sites of EDL muscles in 4-month inbred host animals. Contralateral normally innervated EDL muscles from the same donors were implanted into the opposite legs of the same hosts. Two months after grafting, the muscles were removed and measurements were made in vitro of isometric contractile properties. The grafts were then prepared for morphological analysts. In all cases, the maximum forces generated by innervated grafts of denervated muscles were greater than those generated by denervated muscles. However, when compared with grafts of control muscles in the contralateral limb, grafts of previously denervated muscles showed a steady decline in structural and functional recovery corresponding to the time of previous denervation. The decline was especially pronounced for muscles denervated between 2 and 7 months prior to grafting. Grafts of 7-month denervated muscles were restored to only 17% of the maximum tetanic force of contralateral control grafts compared with 83% for grafts of 2-month denervated muscles. The longer a muscle had been denervated prior to grafting, the higher proportion of thin atrophic muscle fibers it contained. We conclude that grafting into an innervated site improves the mass and maximum force of a muscle over the denervated state, but the longer the period of prior denervation the poorer the recovery of the grafted muscles.