title: Principal strain changes precede ventricular wall thinning during transition to heart failure in a mouse model of dilated cardiomyopathy.
abstract: This study was performed to elucidate the relation between in vivo measurements of two-dimensional principal strains and the progression of left ventricle (LV) wall thinning during development of dilated cardiomyopathy in the protein kinase C-epsilon (PKC-epsilon) transgenic (TG) overexpressing mouse heart. Principal two-dimensional strains, E1 and E2, were determined in the LV wall of the anesthetized mouse using cardiac MRI tagging at 14.1 T. PKC-epsilon TG provided a model of pure dilated cardiomyopathy without evidence of hypertrophy (PKC-epsilon TG, n = 6). Ejection fraction, wall thickness, and principal strains were determined at 1-mo intervals in hearts of PKC-epsilon TG vs. age-matched, nontransgenic mice (NTG, n = 5) from age 6 to 13 mo. Through the study, PKC-epsilon TG displayed lower ejection fraction than NTG. At 7 mo, average principal strain E1 in PKC-epsilon TG hearts was lower compared with NTG (PKC-epsilon TG = 0.14 +/- 0.03, NTG = 0.19 +/- 0.03, P < 0.05). The greatest reductions in regional E1 occurred in the lateral segments. The principal strain E2 did not change significantly in either group. At 9 mo, LV wall thinning occurred in PKC-epsilon TG mice (P < 0.01 vs. 8 mo) to 21% below values in NTG (P < 0.001). Average E1 strain diverged between PKC-epsilon TG and NTG hearts by 25-43%. These E1 changes preceded LV wall thinning and predated the eventual transition from a compensated circumstance to the dilated phenotype. The findings indicate a near step function in E1 depression that precedes the onset of LV wall thinning and suggest E1 as a prognostic indicator of dilated cardiomyopathy.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago College of Medicine, 835 South Wolcott Ave., Chicago, IL 60612, USA.
authors.forename: Janusz H
authors.initials: JH
authors.lastname: Hankiewicz
authors.forename: Paul H
authors.initials: PH
authors.lastname: Goldspink
authors.forename: Peter M
authors.initials: PM
authors.lastname: Buttrick
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006333:Heart Failure / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical; D013318:Stroke Volume; D013997:Time Factors; D015854:Up-Regulation; D016277:Ventricular Function, Left
chemical_list: C497256:Prkce protein, mouse; D051744:Protein Kinase C-epsilon