Principal strain changes precede ventricular wall thinning during transition to heart failure in a mouse model of dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 2008 Jan;294(1):H330-6
Date
10/30/2007Pubmed ID
17965277DOI
10.1152/ajpheart.01109.2007Scopus ID
2-s2.0-38149128702 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
Hankiewicz JH, Goldspink PH, Buttrick PM, Lewandowski EDMESH terms used to index this publication - Major topics in bold
AnimalsCardiomyopathy, Dilated
Disease Models, Animal
Disease Progression
Heart Failure
Heart Ventricles
Magnetic Resonance Imaging
Male
Mice
Mice, Transgenic
Myocardial Contraction
Myocardium
Protein Kinase C-epsilon
Stress, Mechanical
Stroke Volume
Time Factors
Up-Regulation
Ventricular Function, Left