title: Heat stress facilitates the regeneration of injured skeletal muscle in rats.
abstract: BACKGROUND
  Skeletal muscle stem cells, so-called muscle satellite cells, are responsible for the repair and the regeneration of adult skeletal muscle tissues. Heat stress can facilitate the proliferation and the differentiation of myoblasts in vitro and can enhance their proliferative potential, which may stimulate the regrowth of atrophied skeletal muscle. The purpose of this study was to investigate the effect of heat stress on the regeneration of skeletal muscle injury induced by cardiotoxin.
  
  
  METHODS
  Male Wistar rats, aged 7 weeks, were randomly divided into six groups: a nonheated control group that received a physiological saline injection, a group heat stressed before physiological saline injection, a group heat stressed after physiological saline injection, a group injected with cardiotoxin without heat stress, a group heat stressed before cardiotoxin injection, and a group heat stressed after cardiotoxin injection (25 in each group). To initiate muscle injury and regeneration, 0.5 ml of 10 microM cardiotoxin was injected into the left tibialis anterior muscle. Conscious rats in some groups were exposed to environmental heat stress (41 degrees C for 60 min) in a heat chamber 24 h before or immediately after cardiotoxin or physiological saline injection. The heating protocol in the present study causes an increase in the colonic temperature to 41 degrees C. The left tibialis anterior muscles were dissected 1, 3, 7, 14, and 28 days after injection of cardiotoxin or physiological saline.
  
  
  RESULTS
  The wet weight and water content of muscles increased 1 day after cardiotoxin injection regardless of the application of heat stress, but normalized after 7-14 days. The muscle protein content in control rats had increased 7 days after heat stress. Although the muscle protein content decreased on cardiotoxin injection, heat stress caused a significant recovery in protein level. Expression of heat shock protein 72 (HSP72) and the number of Pax7-positive nuclei decreased after cardiotoxin injection but increased on the application of heat stress in both normal control and cardiotoxin-injected groups.
  
  
  CONCLUSIONS
  Heat stress stimulated not only the proliferation of satellite cells but also protein synthesis during the regeneration of injured skeletal muscle. It is thus strongly suggested that the heating of injured skeletal muscle may facilitate recovery. There was no direct relationship between the level of HSP72 expression and muscle protein content, suggesting that HSP72 expression may not be the key signal for protein synthesis in the necrosis-regeneration process.
authors.affiliation: Department of Orthopaedic Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae, Kawasaki, 216-8511, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kojima
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Goto
authors.forename: Shigeta
authors.initials: S
authors.lastname: Morioka
authors.forename: Toshihito
authors.initials: T
authors.lastname: Naito
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Akema
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujiya
authors.forename: Takao
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Ohira
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.forename: Haruhito
authors.initials: H
authors.lastname: Aoki
authors.forename: Toshitada
authors.initials: T
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity; D004195:Disease Models, Animal; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis; D018882:Heat Stress Disorders; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000293:injuries / Q000502:physiology*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*
chemical_list: D004179:Cobra Cardiotoxin Proteins; D050884:HSP72 Heat-Shock Proteins; D009124:Muscle Proteins