The Overall Aim of the Program Project is to understand the biology of the regeneration and transplantation of mammalian skeletal muscle and contribute to improvements in reconstructive surgical procedures involving skeletal muscles. Experiments focus on two significant biological and clinical questions: A) In previously denervated muscles in rats, what factors affect the recovery of structural and functional properties of upon reinnervation? and B) In stabilized free neurovascular-repaired grafts in cats, what mechanisms are responsible for the deficits in structural and functional properties produced by tendon and nerve repair. The properties of the graft are expected to be related to the physical activity of the host cat. We hypothesize that structural and functional properties of reinnervated single muscle fibers in grafts of normal muscle and short-term denervated muscles will not differ from those of single muscle fibers in control muscles, but that differentiation of regenerated muscle fibers derived from long-term denervated muscles will be incomplete. Each of the three projects will have specific responsibilities directed toward the testing of the Group and Individual Hypotheses. The responsibilities will be morphological studies (Project 1), physical activity of host animals and protein analyses of grafts and muscles (Project 2), and muscle mechanics of single fibers, motor units, and whole grafts and muscles (Project 3). An Administrative Core will provide support services, an Animal Core will perform the transplantation operations and post-operative care, and a Statistical Core will provide appropriate statistical procedures and consultant services. The significance of the proposed studies is the resolution of two major clinical problems: 1. determination of the optimum conditions for denervated muscle to regain structure and function upon reinnervation; and 2. clarification of the operative procedures and underlying mechanisms responsible for deficits in large stabilized free neurovascular-repaired grafts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program Projects (P01)
Project #
5P01DE007687-11
Application #
3094987
Study Section
Special Emphasis Panel (SRC (02))
Project Start
1981-09-01
Project End
1995-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Borisov, A B; Carlson, B M (2000) Cell death in denervated skeletal muscle is distinct from classical apoptosis. Anat Rec 258:305-18
Kasper, C E (1999) Recovery of plantaris muscle from impaired physical mobility. Biol Res Nurs 1:4-11
Kasper, C E; Maxwell, L C; White, T P (1996) Alterations in skeletal muscle related to short-term impaired physical mobility. Res Nurs Health 19:133-42
Miller, S W; Opiteck, J A; White, T P et al. (1996) Functional evaluation at the medial gastrocnemius donor site in rats. J Reconstr Microsurg 12:143-7
Devor, S T; White, T P (1996) Myosin heavy chain of immature soleus muscle grafts adapts to hyperthyroidism more than to physical activity. J Appl Physiol 80:789-94
Esser, K A; White, T P (1995) Mechanical load affects growth and maturation of skeletal muscle grafts. J Appl Physiol 78:30-7
Devor, S T; White, T P (1995) Myosin heavy chain phenotype in regenerating skeletal muscle is affected by thyroid hormone. Med Sci Sports Exerc 27:674-81
Miller, S W; Hassett, C A; White, T P et al. (1994) Recovery of medial gastrocnemius muscle grafts in rats: implications for the plantar flexor group. J Appl Physiol 77:2773-7
Stevenson, T R; Kadhiresan, V A; Faulkner, J A (1994) Tubular nerve guide and epineurial repair: comparison of techniques for neurorrhaphy. J Reconstr Microsurg 10:171-4
White, T P; Devor, S T (1993) Skeletal muscle regeneration and plasticity of grafts. Exerc Sport Sci Rev 21:263-95

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