title: A novel cardiac muscle-derived biomaterial reduces dyskinesia and postinfarct left ventricular remodeling in a mouse model of myocardial infarction.
abstract: Extracellular matrix (ECM) degradation after myocardial infarction (MI) leaves the myocardium structurally weakened and, as a result, susceptible to early infarct zone dyskinesia and left ventricular (LV) remodeling. While various cellular and biomaterial preparations have been transplanted into the infarct zone in hopes of improving post-MI LV remodeling, an allogeneic cardiac muscle-derived ECM extract has yet to be developed and tested in the setting of reperfused MI. We sought to determine the effects of injecting a novel cardiac muscle-derived ECM into the infarct zone on early dyskinesia and LV remodeling in a mouse model of MI. Cardiac muscle ECM was extracted from frozen mouse heart tissue by a protocol that enriches for basement membrane constituents. The extract was injected into the infarct zone immediately after ischemia/reperfusion injury (n = 6). Echocardiography was performed at baseline and at days 2, 7, 14, and 28 post-MI to assess 3D LV volumes and cardiac function, as compared to infarcted controls (n = 9). Early infarct zone dyskinesia was measured on day 2 post-MI using a novel metric, the dyskinesia index. End-systolic volume was significantly reduced in the ECM-treated group compared to controls by day 14. Ejection fraction and stroke volume were also significantly improved in the ECM-treated group. ECM-treated hearts showed a significant (P < 0.005) reduction in dyskinetic motion on day 2. Thus, using high-frequency ultrasound, it was shown that treatment with a cardiac-derived ECM preparation reduced early infarct zone dyskinesia and post-MI LV remodeling in a mouse model of reperfused MI.
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: O'Connor
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
authors.forename: Nivedita K
authors.initials: NK
authors.lastname: Naresh
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Piras
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Smith
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia Department of Radiology, University of Virginia, Charlottesville, Virginia.
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Epstein
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
authors.forename: John A
authors.initials: JA
authors.lastname: Hossack
authors.affiliation: School of Medical Diagnostic and Translational Sciences, College of Health Sciences, Old Dominion University, Norfolk, Virginia.
authors.forename: Roy C
authors.initials: RC
authors.lastname: Ogle
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia Department of Radiology, University of Virginia, Charlottesville, Virginia bf4g@virginia.edu.
authors.forename: Brent A
authors.initials: BA
authors.lastname: French
keywords: Extracellular matrix; left ventricular remodeling; myocardial infarction; small animal imaging; speckle tracking echocardiography
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