title: Wound healing in the mitral valve.
abstract: OBJECTIVE
  Limited information is available on the healing of wounds in the mitral valve. In the present study, this process has been evaluated in young sheep.
  
  
  METHODS
  Histologic, histochemical and transmission electron microscopic studies were made of the healing of wounds produced surgically under cardiopulmonary bypass, in the mitral valve (a 1 cm-long radially oriented incision at the free edge of the anterior leaflet) of young sheep (n = 11).
  
  
  RESULTS
  All animals developed severe mitral regurgitation, as demonstrated by hemodynamic, ultrasound and ventriculographic studies. At four to five weeks, the edges of the incision were only partially covered by endothelium and had small deposits of fibrin. Two types of granulation tissue were associated with wound healing. The first covered the cut edge and consisted of myxoid tissue that extended from the valvular spongiosa and fibrosa; the second type consisted of spindle-shaped cells arranged parallel to the surface and surrounded by a slightly myxoid stroma. This granulation tissue resembled that caused by reactive fibrosis in regurgitant mitral valves. The connective tissue cells in granulation tissue developed increasing amounts of actin-like filaments as a function of time after operation. This differentiation resulted in the development of myofibroblasts. In contrast to the avascular nature of normal mitral leaflets, capillaries and arterioles first appeared in the middle portion of the leaflet at eight weeks, and at the proximal edges of the wounds at 12 weeks.
  
  
  CONCLUSIONS
  The healing of mitral valvular wounds is a slow process that requires between eight and 12 weeks for the formation of a dense collagenous scar at the edges and complete restoration of the endothelial lining. Progression of healing is associated with the phenotypic modulation of connective tissue cells from fibroblasts to myofibroblasts and neovascularization of the leaflets.
authors.affiliation: Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.forename: I
authors.initials: I
authors.lastname: Yamada
authors.forename: V J
authors.initials: VJ
authors.lastname: Ferrans
mesh_terms: D003238:Connective Tissue / Q000473:pathology; D005260:Female; D006097:Granulation Tissue / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008943:Mitral Valve / Q000473:pathology*; D008944:Mitral Valve Insufficiency / Q000473:pathology*; D014945:Wound Healing