Department of Mechanical Engineering, Stanford, CA, USA.
J Mech Behav Biomed Mater. 2012 Nov;15:208-17. doi: 10.1016/j.jmbbm.2012.07.001. Epub 2012 Jul 10.
Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. Recent studies suggest that mitral leaflets have the potential to grow and reduce the degree of regurgitation. Leaflet growth has been associated with papillary muscle displacement, but role of annular dilation in leaflet growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced by papillary muscle tethering and annular dilation, triggers chronic leaflet growth. To decipher the mechanisms that drive the growth process, we further quantified regional and directional variations of growth. Five adult sheep underwent coronary snare and marker placement on the left ventricle, papillary muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the snares to create inferior myocardial infarction. We recorded marker coordinates at baseline, acutely (immediately post-infarction), and chronically (five weeks post-infarction). From these coordinates, we calculated acute and chronic changes in ventricular, papillary muscle, and annular geometry along with acute and chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p<0.001) induced chronic posterior papillary muscle displacement of 13.49 mm (p=0.07). Chronic mitral annular area, commissural and septal-lateral distances increased by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area, circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non-significant regional variations (p=0.868). Our study demonstrates that mechanical stretch, induced by annular dilation and papillary muscle tethering, triggers mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may open new avenues to pharmacologically or surgically manipulate mechanotransduction pathways to augment mitral leaflet area and reduce the degree of regurgitation.
缺血性二尖瓣反流是由心肌梗死引起的二尖瓣关闭不全。最近的研究表明，二尖瓣瓣叶具有生长的潜力，可以减少反流程度。瓣叶生长与乳头肌移位有关，但瓣环扩张在瓣叶生长中的作用尚不清楚。我们假设，通过乳头肌固定和瓣环扩张引起的慢性瓣叶拉伸会引发慢性瓣叶生长。为了解释驱动生长过程的机制，我们进一步量化了生长的区域和方向变化。五只成年绵羊在左心室、乳头肌、二尖瓣环和二尖瓣瓣叶上进行了冠状动脉套扎和标记放置。八天后，我们收紧套扎线以造成下壁心肌梗死。我们在基线、急性（心肌梗死后立即）和慢性（心肌梗死后五周）记录标记坐标。从这些坐标中，我们计算了心室、乳头肌和瓣环几何形状的急性和慢性变化以及急性和慢性瓣叶应变。左心室慢性扩张 17.15%（p<0.001）导致慢性后乳头肌位移 13.49 毫米（p=0.07）。慢性二尖瓣环面积、二尖瓣环前后和左右距离分别增加了 32.50%（p=0.010）、14.11%（p=0.007）和 10.84%（p=0.010）。慢性面积、环向和径向生长分别为 15.57%、5.91%和 3.58%，且无明显的区域变化（p=0.868）。我们的研究表明，瓣环扩张和乳头肌固定引起的机械拉伸会引发二尖瓣瓣叶生长。了解瓣叶适应的机制可能为通过药理学或手术手段操纵机械转导途径以增加二尖瓣瓣叶面积和减少反流程度开辟新途径。
