title: Impaired contractile reserve in severe mitral valve regurgitation with a preserved ejection fraction.
abstract: BACKGROUND
  Impaired contractile reserve in chronic MR results from load-independent, myocyte contractile abnormalities.
  
  
  OBJECTIVE
  Investigate the mechanisms of contractile dysfunction in chronic mitral valve regurgitation (MR).
  
  
  METHODS
  Mild MR was produced in eight dogs followed by pacing induced left ventricular (LV) dilatation over eight months. In-vivo LV dP/dt was measured at several pacing rates. Contractile function was measured in isolated LV trabeculae and myocytes at several stimulation rates and during changes in extracellular [Ca2+]. Identical studies were performed with six control dogs.
  
  
  RESULTS
  Chronic MR resulted in a preserved ejection fraction with decreased dP/dt (p<0.01). LV trabeculae demonstrated significantly lower developed force and a negative force-frequency relation with chronic MR (p<0.05). Myocytes exhibited a negative shortening-frequency relationship in both groups with a greater decline with chronic MR (p<0.001) paralleled by decreases in peak [Ca2+](i) transients. Increases in extracellular [Ca2+] abrogated the defects in force generation in trabeculae from animals with chronic MR.
  
  
  CONCLUSIONS
  Even with a preserved EF, chronic severe MR results in a significant reduction in intrinsic contractile function and reserve. Functional impairment was load-independent reflecting a predominant defect in calcium cycling rather than impaired peak force generating capacity due to myofibrillar attenuation.
authors.affiliation: Cardiovascular Research Center, Temple University School of Medicine, United States. mcginleyjoseph@hotmail.com
authors.forename: Joseph C
authors.initials: JC
authors.lastname: McGinley
authors.forename: Remus M
authors.initials: RM
authors.lastname: Berretta
authors.forename: Khuram
authors.initials: K
authors.lastname: Chaudhary
authors.forename: Eric
authors.initials: E
authors.lastname: Rossman
authors.forename: George D
authors.initials: GD
authors.lastname: Bratinov
authors.forename: John P
authors.initials: JP
authors.lastname: Gaughan
authors.forename: Steven
authors.initials: S
authors.lastname: Houser
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Margulies
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004108:Dilatation, Pathologic / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008944:Mitral Valve Insufficiency / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000502:physiology*; D013318:Stroke Volume / Q000502:physiology*