Regional dysfunction correlates with myofiber disarray in transgenic mice with ventricular expression of ras

A hallmark of certain cardiac diseases such as familial hypertrophic cardio myopathy is focal myofiber disarray. Regional ventricular dysfunction occur s in human subjects with hypertrophic cardiomyopathy; however, no direct ev idence exists to correlate regional dysfunction with myofiber disarray. We used a transgenic mouse, which exhibits regional myofiber disarray via vent ricular expression of the human oncogene ras, to investigate the relationsh ip between myofiber disarray and septal surface strain. An isolated ejectin g mouse heart preparation was used to record deformation of markers on the septal surface and to determine nonhomogeneous septal surface strain maps. Myofiber disarray made in histological tissue sections was correlated with gradients in surface systolic shortening. Significantly smaller maximum pri ncipal shortening was associated with disarray located near the right ventr icle (RV) septal surface. There was also significantly smaller surface shea r strain associated with disarray located either near the RV surface or at the midwall. Because surface shear is a local indicator of torsion, we conc lude that myofiber disarray is associated with reduced septal torsion and r educed surface shortening.