title: Myosin heavy chain isoform profiles remain altered at 7 months if the lacerated medial gastrocnemius is poorly reinnervated: a study in rabbits.
abstract: Lacerated skeletal muscles often do not recover full function after repair. Denervated muscles with altered myosin heavy chain isoform (MHC) profiles are known to result in functional impairment. We studied the functional recovery of lacerated muscles, assessing MHC profile changes in association to the involvement of the intramuscular nerve (IM). We tested three lacerated models using the rabbit's medial gastrocnemius where the IM was either cut (NNR), repaired (NR), or preserved intact (NP). Muscles were assessed 7 months after repair for muscle atrophy, isometric contraction (by electrical stimulation), and fibrosis formation at the lesion site. Changes in myofibrillar actomyosin adenosine triphosphatase activity, MHC profile, regenerating myofibers and reinnervation were assessed by Western blot, histology, or immunohistology. Lacerated muscles with a repaired (NR) or an intact (NP) IM showed good recovery, with no significant changes in the MHC profile. Muscles where the IM was not repaired (NNR) resulted in significant scar area at the lesion site (p < 0.05), muscle atrophy (67%, p < 0.05) and loss in contractile properties (63% of the uninjured side, p < 0.05). At 7 months, all muscles were reinnervated. However, the NNR had an inappropriate (polyneural) and poorly distributed reinnervation, the presence of regenerating myofibers, and demonstrated a fast-to-slow MHC transition (71%:29% to 44%:56%, ANOVA, p = 0.018). This was associated to the cut IM when the NNR muscle was lacerated. Poor reinnervation in lacerated skeletal muscles alters the myosin heavy chain profile permanently. This study provides a rationale to also consider biological solutions to improve nerve regeneration and reinnervation in the surgical repair of lacerated muscles.
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. dosbarry@nus.edu.sg
authors.forename: Barry P
authors.initials: BP
authors.lastname: Pereira
authors.forename: Hwan Chour
authors.initials: HC
authors.lastname: Han
authors.forename: Zou
authors.initials: Z
authors.lastname: Yu
authors.forename: Bee-Leng
authors.initials: BL
authors.lastname: Tan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ling
authors.forename: Ashvin
authors.initials: A
authors.lastname: Thambyah
authors.forename: Saminathan S
authors.initials: SS
authors.lastname: Nathan
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D009045:Motor Endplate / Q000201:enzymology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000293:injuries* / Q000294:innervation*; D018995:Myosin Heavy Chains / Q000032:analysis*; D009416:Nerve Regeneration; D020033:Protein Isoforms; D011817:Rabbits
chemical_list: D020033:Protein Isoforms; D000110:Acetylcholinesterase; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains