title: Regional septal dysfunction in a three-dimensional computational model of focal myofiber disarray.
abstract: MLC2v/ras transgenic mice display a phenotype characteristic of hypertrophic cardiomyopathy, with septal hypertrophy and focal myocyte disarray. Experimental measurements of septal wall mechanics in ras transgenic mice have previously shown that regions of myocyte disarray have reduced principal systolic shortening, torsional systolic shear, and sarcomere length. To investigate the mechanisms of this regional dysfunction, a three-dimensional prolate spheroidal finite-element model was used to simulate filling and ejection in the hypertrophied mouse left ventricle with septal disarray. Focally disarrayed septal myocardium was modeled by randomly distributed three-dimensional regions of altered material properties based on measured statistical distributions of muscle fiber angular dispersion. Material properties in disarrayed regions were modeled by decreased systolic anisotropy derived from increased fiber angle dispersion and decreased systolic tension development associated with reduced sarcomere lengths. Compared with measurements in ras transgenic mice, the model showed similar heterogeneity of septal systolic strain with the largest reductions in principal shortening and torsional shear in regions of greatest disarray. Average systolic principal shortening on the right ventricular septal surface of the model was -0.114 for normal regions and -0.065 for disarrayed regions; for torsional shear, these values were 0.047 and 0.019, respectively. These model results suggest that regional dysfunction in ras transgenic mice may be explained in part by the observed structural defects, including myofiber dispersion and reduced sarcomere length, which contributed about equally to predicted dysfunction in the disarrayed myocardium.
authors.affiliation: Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, La Jolla, California 92093-0412, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Usyk
authors.forename: J H
authors.initials: JH
authors.lastname: Omens
authors.forename: A D
authors.initials: AD
authors.lastname: McCulloch
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D011905:Genes, ras; D006321:Heart / Q000503:physiopathology*; D021621:Imaging, Three-Dimensional; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009200:Myocardial Contraction