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.
Highlights
In its acute stage, myocardial infarction (MI) results in immediate death to cardiomyocytes and contractile dysfunction
Mortality during surgery and over the course of the imaging period was similar in control and cMatrix-treated groups: one mouse from the control group died on day 3 post-MI after a poor recovery from surgery, and a cMatrix-treated mouse had to be killed during the last week of the study due to inadvertent injury
This study describes the preparation and evaluation of cMatrix, a novel cardiac muscle-derived biomaterial
Summary
Myocardial infarction (MI) results in immediate death to cardiomyocytes and contractile dysfunction. Immune cells infiltrate the area of infarction to phagocytize necrotic cells and apoptotic cell debris, and release enzymes that degrade the cardiac extracellular matrix (ECM) (Dai et al 2005; French and Kramer 2007; Jourdan-Lesaux et al 2010). This causes the infarct zone to become thinned, structurally weak, and susceptible to paradoxical bulging under the pressure of systole (early dyskinesia) (Dai et al 2005; French and Kramer 2007; Gersh et al 2009) prior to scar formation.
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