Submitted on September 24, 2007
Accepted on October 20, 2007
Principal Strain Changes Precede Ventricular Wall Thinning During Transition to Heart Failure in a Mouse Model of Dilated Cardiomyopathy
Janusz H. Hankiewicz1, Paul H Goldspink1, Peter M. Buttrick1, and E. Douglas Lewandowski1*
1 Center for Cardiovascular Research, University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States
* To whom correspondence should be addressed. E-mail: dougl{at}uic.edu.
This study was performed to elucidate the relation between in vivo measurements of 2D principal strains and the progression of left ventricle (LV) wall thinning during development of dilated cardiomyopathy in the protein kinase C
(PKC TG) overexpressing mouse heart. Principal 2D strains, E1 and E2, were determined in the LV wall of the anesthetized mouse using cardiac MRI tagging at 14.1 T. PKC TG provided a model of pure dilated cardiomyopathy without evidence of hypertrophy (PKC ) TG, n=6). Ejection fraction (EF), wall thickness and principal strains were determined at one month intervals in hearts of PKC TG versus age-matched, non-transgenic mice (NTG, n=5) from age 6 to 13 months. Through the study PKC TG displayed lower EF than NTG. At 7 months, average principal strain E1 in PKC TG hearts was lower compared to NTG (PKC TG=0.14±0.03, NTG=0.19±0.03, P<0.05). Greatest reductions in regional E1 occurred in the lateral segments. The principal strain E2 did not change significantly in either group. At 9 months, LV wall thinning occurred in PKC TG mice (P<0.01 vs. 8 mos) to 21% below values in NTG (P<0.001). Average E1 strain diverged between PKC 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.
