O'Connor Daniel M, Naresh Nivedita K, Piras Bryan A, Xu Yaqin, Smith Robert S, Epstein Frederick H, Hossack John A, Ogle Roy C, French Brent A
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia.
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia Department of Radiology, University of Virginia, Charlottesville, Virginia.
Physiol Rep. 2015 Mar;3(3). doi: 10.14814/phy2.12351.
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.
心肌梗死（MI）后细胞外基质（ECM）降解会使心肌结构变弱，进而易发生早期梗死区运动障碍和左心室（LV）重塑。尽管已将各种细胞和生物材料制剂移植到梗死区，以期改善心肌梗死后的左心室重塑，但同种异体心肌源性ECM提取物尚未在再灌注心肌梗死的情况下得到开发和测试。我们试图确定在心肌梗死小鼠模型中，将一种新型心肌源性ECM注入梗死区对早期运动障碍和左心室重塑的影响。通过富集基底膜成分的方案从冷冻的小鼠心脏组织中提取心肌ECM。在缺血/再灌注损伤后立即将提取物注入梗死区（n = 6）。与梗死对照组（n = 9）相比，在心肌梗死后的基线以及第2、7、14和28天进行超声心动图检查，以评估左心室三维容积和心脏功能。在心肌梗死后第2天，使用一种新的指标——运动障碍指数来测量早期梗死区运动障碍。到第14天，与对照组相比，ECM治疗组的收缩末期容积显著降低。ECM治疗组的射血分数和每搏输出量也显著改善。在第2天，ECM治疗的心脏显示运动障碍性运动显著减少（P < 0.005）。因此，使用高频超声显示，在再灌注心肌梗死小鼠模型中，用心脏源性ECM制剂治疗可减少早期梗死区运动障碍和心肌梗死后的左心室重塑。
