Abstract 10896: A Novel Cardiac Muscle-Derived Extracellular Matrix Extract Reduces Dyskinesia and Post-Infarct Left Ventricular Remodeling in a Mouse Model of Myocardial Infarction
Introduction: Extracellular matrix (ECM) degradation following MI leaves the myocardium thinned and structurally weakened. As a result, it is susceptible to LV remodeling and early dyskinesia, an important component of cardiac dyssynchrony. We hypothesized that injecting a novel cardiac muscle-derived ECM extract into the infarct zone would reduce early dyskinesia and LV remodeling in a mouse model of MI.
Methods: Cardiac muscle ECM was extracted from frozen mouse heart tissue by a modified Matrigel protocol. 15µL of ECM were injected into the infarct zone directly after reperfusion (n=6). Echocardiography was performed at baseline and at days 2, 7, 14, & 28 after MI to assess LV volumes and cardiac function compared to infarcted mice that received no injection (n=9). Early infarct zone dyskinesia was measured at day 2 post-MI using a short-axis slice 2 mm superior to the apex of the LV. Speckle tracking was used to obtain radial displacements for 96 segments. A new metric, the dyskinesia index (DI), was used to quantify this data. DI is the average value of the ratio of the sum of signed radial displacements to the sum of unsigned radial displacements, for each time point in the cardiac cycle (t0 to tN; Eq. 1). In this equation, d is the radial displacement of each segment i at time point t. A DI of 1 represents completely polar radial displacement and smaller values indicate increasing dyskinetic motion.
Results: ESV was significantly reduced in the ECM treated group by day 14, compared to controls (Panel A). EF and SV were also significantly greater in the ECM treated group (Panels B & C). ECM treated hearts showed a significant (p<0.005) reduction in dyskinetic motion on day 2, represented as a higher DI (Panel D). All data is presented as mean ± SEM, where * denotes p<0.05 vs. infarcted controls.
Conclusions: Using high frequency ultrasound, a novel cardiac muscle-derived ECM extract was shown to reduce early infarct zone dyskinesia and post-MI LV remodeling in a mouse model of reperfused MI.
- © 2011 by American Heart Association, Inc.