Abstract P2008.1: Association Of Myocardial Stiffening With Impaired Relaxation In A Diabetic Murine Model Of Left Ventricular Diastolic Dysfunction

Abstract

Introduction: Left ventricular diastolic dysfunction (LVDD) is often manifested by impaired relaxation and myocardial stiffening in the left ventricle (LV). While impairments in the function of myofilament regulatory proteins are known to deteriorate LV relaxation, the effects of passive myocardial stiffening on the relaxation of active forces remain unknown. Methods: A diabetic murine model of LVDD (db/db, n=5) and wild-type mice (WT, n=5) were used to study the association between tissue-level passive stiffness and organ-level relaxation. Early transmitral flow velocity to mitral annular tissue velocity ratio (E/e’), measured by Doppler imaging, was used to assess LV relaxation. Cardiac magnetic resonance imaging was performed using a 7T Bruker scanner to estimate diastolic strains via image registration. Mechanical testing was performed on harvested LV free wall (LVFW) specimens to measure passive stiffness. Results: LVDD was confirmed by a high septal E/e’ ratio (Fig. 1A). The db/db mice presented an increase in passive LVFW stiffness measured as the tangent to the circumferential stress-strain curve at 30% strain (Fig. 1B). A positive correlation was observed between passive stiffness and E/e’ (Fig. 1C). End-diastolic strain calculations (Fig. 1D) corroborated LV filling impairment indicating significant reductions in circumferential LV strains (Fig. 1E). Conclusion: Passive stiffening may impair LV filling by not only restraining the passive stretch of the myocardium at diastole but also by decelerating the active relaxation. Further integrated in-vivo and ex-vivo studies of LVDD can deconvolute the “active” and “passive” causes of impaired relaxation.