Regional septal dysfunction in a three-dimensional computational model of focal myofiber disarray

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Biomedical Engineering

Background:

• MLC2v/ras transgenic mice exhibit hypertrophic cardiomyopathy with septal hypertrophy and myocyte disarray.
• Previous studies show reduced systolic function and sarcomere length in disarrayed regions of these mice.

Purpose of the Study:

• To investigate the mechanisms of regional cardiac dysfunction in hypertrophied mouse left ventricles with septal disarray.
• To simulate ventricular filling and ejection using a finite-element model.

Main Methods:

• A 3D prolate spheroidal finite-element model was developed to simulate left ventricular function.
• Disarrayed septal myocardium was modeled with altered material properties reflecting statistical distributions of fiber angle dispersion.
• Reduced systolic anisotropy and tension development were incorporated based on reduced sarcomere lengths.

Main Results:

• The model replicated the heterogeneity of septal systolic strain observed in ras transgenic mice.
• Regions with greater myocyte disarray showed the largest reductions in principal shortening and torsional shear.
• Average systolic principal shortening was -0.114 in normal vs. -0.065 in disarrayed regions; torsional shear was 0.047 vs. 0.019.

Conclusions:

• Regional dysfunction in ras transgenic mice can be partly explained by structural defects like myofiber dispersion and reduced sarcomere length.
• Both myofiber dispersion and reduced sarcomere length contributed approximately equally to the predicted dysfunction in disarrayed myocardium.