title: Early left ventricular remodeling in acute severe aortic regurgitation: insights from an animal model.
abstract: OBJECTIVE
  Chronic aortic regurgitation (AR) induces left ventricular (LV) hypertrophy and eventually LV dysfunction. While the effects of chronic AR on the left ventricle are well known, the effects of acute AR have not been adequately evaluated. It was hypothesized that the LV tissues would be rapidly remodeled by acute AR, and that the renin-angiotensin system would be involved in that acute remodeling.
  
  
  METHODS
  The early LV adaptations to acute AR were evaluated serially over a period of 14 days, using a rat model. Adaptations were evaluated in vivo by echocardiography, and in vitro on explanted heart tissue after one, two, or 14 days.
  
  
  RESULTS
  After 14 days, the left ventricle of AR rats was already significantly hypertrophied and dilated (end-diastolic diameter +16% (p <0.05) versus sham; LV mass +16% (p <0.01) versus sham). A short and transient increase in fractional shortening was observed during the first 48 h after AR induction. The cardiomyocyte cross-sectional area and perivascular fibrosis were significantly increased after 14 days of AR. The number of fibronectin-positive cells in LV sections rapidly increased, as did the fibronectin protein and mRNA content of LV crude homogenates. The expression of pro-matrix metalloproteinase 2 was clearly abnormal after two days. Significant shifts in the expression of angiotensin II receptors were also detected as early as one 1 day.
  
  
  CONCLUSIONS
  Significant macroscopic and microscopic abnormalities were present in the left ventricle of rats with acute AR, soon after its induction. Considerable hypertrophy, perivascular fibrosis and extracellular matrix (ECM) remodeling were present after only 14 days. These results suggest that, in AR, the myocytes and ECM are affected significantly at a very early stage of the disease.
authors.affiliation: Groupe de Recherche sur les Valvulopathies, Centre de Recherche Hôpital Laval, Institut de cardiologie de Québec, Université Laval, Quebec City, Canada.
authors.forename: Dominic
authors.initials: D
authors.lastname: Lachance
authors.forename: Eric
authors.initials: E
authors.lastname: Plante
authors.forename: Elise
authors.initials: E
authors.lastname: Roussel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Drolet
authors.forename: Jacques
authors.initials: J
authors.lastname: Couet
authors.forename: Marie
authors.initials: M
authors.lastname: Arsenault
mesh_terms: D000208:Acute Disease; D000818:Animals; D001022:Aortic Valve Insufficiency / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D005353:Fibronectins; D011945:Receptors, Angiotensin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C092073:cardiotrophin 1; D007703:Peptidyl-Dipeptidase A