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Regenerative response of fast and slow twitch skeletal muscle to denervation and devascularization Bockhold, Kathy


The contractile properties of denervated/devascularized mouse fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) were studied at 3, 6, 9, and 12 weeks post-surgery. A comprehensive examination of these physiological parameters is desired in order to establish a mouse model of regeneration. The surgical technique involved shimmying a piece of silk thread along the belly of the muscle thus severing the nervous and the vascular supply to the individual EDL or SOL muscles. The denervated/devascularized muscles were divided into two groups, reinnervated and non-reinnervated based on their twitch and tetanic tensions. During the 12 week period post-denervation/devascularization, reinnervated EDL and SOL muscles showed a gradual increase toward control values in twitch and tetanic tensions. By 12 weeks the SOL reached 107% and 98% of the control twitch and tetanic tensions. In contrast, the reinnervated EDL only recovered 52% of the twitch tension and 64% of the tetanic tension by 12 weeks post-denervation/devascularization. The non-reinnervated SOL twitch and tetanic tensions were significantly less than control (p<0.05) and reinnervated values at 6 and 9 weeks but by 12 weeks they were not different from controls (p<0.05). The non-reinnervated EDL produced significantly less twitch and tetanic tension at all time periods studied. At 3 and 6 weeks post-surgery the reinnervated EDL contracted very slowly, but the speed of contraction gradually increased to control values by 12 weeks. The non-reinnervated EDL was significantly slower than the control and reinnervated muscles. The reinnervated and non-reinnervated SOL were slower than control muscles at 9 weeks but they recovered to control values by 12 weeks. The post-tetanic potentiation (PTP) of reinnervated and non-reinnervated EDL was 20% by 12 weeks and there was no PTP for reinnervated SOL. The maximum velocity of shortening (Vo) for EDL and SOL remained unchanged at all ages. The non-reinnervated and reinnervated EDL muscles were more fatigue resistant than the controls at 3 weeks post-surgery but the reinnervated EDL eventually returned to control values (at 6,9, and 12 weeks post-surgery). The reinnervated and non-reinnervated SOL were significantly less fatigable than controls at 3, 6, and 9 weeks, after which there was no difference in fatigability between the three groups. Both the reinnervated EDL and SOL muscles successfully regenerated as measured by their contractile properties. The non-reinnervated EDL resembled classically denervated muscle. The non-reinnervated SOL reveals a PTP and a fatigue pattern suggestive of reinnervation by a branch of a fast nerve.

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