title: The reduction of hemodynamic loading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment.
abstract: OBJECTIVE
  Mitotic cardiomyocytes and cardiac stem cells have been identified recently in adult hearts, and both have been found to be increased in acute infarcted myocardium. Although these findings suggest potential self-repair of the heart after injury, obvious self-regeneration of the injured heart has never been observed clinically. We hypothesized that hemodynamic loading impairs myocardial repair.
  
  
  METHODS
  Myocardial infarction was induced in C57BL/6 mice by ligating the left anterior descending artery. After 60 minutes, either the infarcted heart was transplanted heterotopically into a healthy recipient C57BL/6 mouse to remove the ventricular hemodynamic loading (unloading group) or it was left as an infarcted heart under normal hemodynamic loading conditions in the same mouse (loading group). The infarcted hearts were dissected for histologic analysis after 3, 7, 14, and 28 days.
  
  
  RESULTS
  Histologic analysis showed that the wall thickness of the infarcted left ventricle was significantly greater and the area of infarction was significantly smaller in the unloading group than in the loading group. Immunostaining analysis revealed significantly more Ki-67-positive cells and significantly fewer apoptotic cells in the infarcted myocardium in the unloading group than in the loading group. There were also significantly more c-kit- and Sca-1-positive stem cells in the infarcted myocardium in the unloading group than in the loading group.
  
  
  CONCLUSIONS
  Our findings suggest that hemodynamic unloading assists self-regeneration of the injured heart by increasing cell proliferation, inhibiting cell apoptosis, and inducing stem-cell recruitment.
authors: Department of Surgery and Clinical Science, Division of Cardiac Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Ryo
authors: R
authors: Suzuki
authors: Tao-Sheng
authors: TS
authors: Li
authors: Akihito
authors: A
authors: Mikamo
authors: Masaya
authors: M
authors: Takahashi
authors: Mako
authors: M
authors: Ohshima
authors: Masayuki
authors: M
authors: Kubo
authors: Hiroshi
authors: H
authors: Ito
authors: Kimikazu
authors: K
authors: Hamano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000502:physiology; D012038:Regeneration; D013234:Stem Cells / Q000502:physiology; D017725:Ventricular Pressure / Q000502:physiology*