title: Regenerative healing following foetal myocardial infarction.
abstract: OBJECTIVE
  The adult response to myocardial infarction results in inflammation, scar formation, left ventricular dilatation, and loss of regional and global function. Regenerative scarless healing has been demonstrated in foetal dermis and tendon and is associated with diminished inflammation. We hypothesised that following foetal myocardial infarction, there would be minimal inflammation, regenerative healing, and preservation of function.
  
  
  METHODS
  Anteroapical myocardial infarction encompassing 20% of the left ventricle was created in adult or early gestation foetal sheep. Myocardial function was serially assessed using quantitative echocardiography. Infarct architecture was examined histologically for evidence of scar formation. Cellular inflammation, cellular proliferation, and apoptosis were assessed using immunohistochemistry.
  
  
  RESULTS
  In the adult sheep 4 weeks following myocardial infarction, there was a significant decline in ejection fraction (EF) (41±7.4% to 26±7.4%, p<0.05), and the akinetic myocardial segment increased in size (6.9±0.8 cm to 7.9±1.1 cm, p<0.05). By contrast, there was no decline in the foetal EF (53±8.1% to 55±8.8%) and no akinetic foetal myocardial segment 4 weeks post-infarction. The foetal infarcts lacked an inflammatory cell infiltrate and healed with minimal fibrosis, compared with the adults. Foetal infarcts also demonstrated 5-bromo-2'-deoxyuridine (BrdU)+ proliferating cells, including cardiomyocytes, within the infarct.
  
  
  CONCLUSIONS
  These data demonstrate that the foetal response to myocardial infarction is dramatically different from the adult and is characterised by minimal inflammation, lack of fibrosis, myocardial proliferation and restoration of cardiac function. Diminished inflammation is associated with foetal regenerative cardiac healing following injury. Understanding the mechanisms involved in foetal myocardial regeneration may lead to applications to alter the adult response following myocardial infarction.
authors.affiliation: The University of Pennsylvania School of Medicine, Philadelphia, PA, USA. benjamin.herdrich@uphs.upenn.edu
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Herdrich
authors.forename: Enrico
authors.initials: E
authors.lastname: Danzer
authors.forename: Marcus G
authors.initials: MG
authors.lastname: Davey
authors.forename: Myron
authors.initials: M
authors.lastname: Allukian
authors.forename: Virginia
authors.initials: V
authors.lastname: Englefield
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002921:Cicatrix / Q000473:pathology; D004195:Disease Models, Animal; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D005318:Fetal Heart / Q000502:physiology*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000502:physiology
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