title: Variable phenotype in murine transverse aortic constriction.
abstract: BACKGROUND
  In mice, transverse aortic constriction (TAC) is variably characterized as a model of pressure overload-induced hypertrophy (left ventricular [LV] hypertrophy, or LVH) or heart failure (HF). While commonly used, variability in the TAC model is poorly defined. The objectives of this study were to characterize the variability in the TAC model and to define a simple, noninvasive method of prospectively identifying mice with HF versus compensated LVH after TAC.
  
  
  METHODS
  Eight-week-old male C57BL/6J mice underwent TAC or sham and then echocardiography at 3 weeks post-TAC. A group of sham and TAC mice were euthanized after the 3-week echocardiogram, while the remainder underwent repeat echocardiography and were euthanized at 9 weeks post-TAC. The presence of TAC was assessed with two-dimensional echocardiography, anatomic aortic m-mode and color flow, and pulsed-wave Doppler examination of the transverse aorta (TA) and by LV systolic pressure (LVP). Trans-TAC pressure gradient was assessed invasively in a subset of mice. HF was defined as lung/body weight>upper limit in sham-operated mice.
  
  
  RESULTS
  As compared with sham, TAC mice had higher TA velocity, LVP and LV weight, and lower ejection fraction (EF) at 3 or 9 weeks post-TAC. Only a subset of TAC mice (28%) developed HF. As compared with compensated LVH, HF mice were characterized by similar TA velocity and higher percent TA stenosis, but lower LVP, higher LV weight, larger LV cavity, lower EF and stress-corrected midwall fiber shortening, and more fibrosis. Both EF and LV mass measured by echocardiography at 3 weeks post-TAC were predictive of the presence of HF at 3 or 9 weeks post-TAC.
  
  
  CONCLUSIONS
  In wild-type mice, TAC produces a variable cardiac phenotype. Marked abnormalities in LV mass and EF at echocardiography 3 weeks post-TAC identify mice with HF at autopsy. These data are relevant to appropriate design and interpretation of murine studies.
authors.affiliation: Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Selma F
authors.initials: SF
authors.lastname: Mohammed
authors.forename: Jimmy R
authors.initials: JR
authors.lastname: Storlie
authors.forename: Elise A
authors.initials: EA
authors.lastname: Oehler
authors.forename: Lorna A
authors.initials: LA
authors.lastname: Bowen
authors.forename: Josef
authors.initials: J
authors.lastname: Korinek
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology*; D001835:Body Weight; D003251:Constriction, Pathologic / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004562:Electrocardiography; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010641:Phenotype; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000503:physiopathology