Klepach Doron, Lee Lik Chuan, Wenk Jonathan F, Ratcliffe Mark B, Zohdi Tarek I, Navia Jose A, Kassab Ghassan S, Kuhl Ellen, Guccione Julius M
Department of Surgery, Division of Adult Cardiothoracic Surgery, UC San Francisco, San Francisco, CA 94121, USA.
Mech Res Commun. 2012 Jun 1;42:134-141. doi: 10.1016/j.mechrescom.2012.03.005. Epub 2012 Mar 12.
Cardiac growth and remodeling in the form of chamber dilation and wall thinning are typical hallmarks of infarct-induced heart failure. Over time, the infarct region stiffens, the remaining muscle takes over function, and the chamber weakens and dilates. Current therapies seek to attenuate these effects by removing the infarct region or by providing structural support to the ventricular wall. However, the underlying mechanisms of these therapies are unclear, and the results remain suboptimal. Here we show that myocardial infarction induces pronounced regional and transmural variations in cardiac form. We introduce a mechanistic growth model capable of predicting structural alterations in response to mechanical overload. Under a uniform loading, this model predicts non-uniform growth. Using this model, we simulate growth in a patient-specific left ventricle. We compare two cases, growth in an infarcted heart, pre-operative, and growth in the same heart, after the infarct was surgically excluded, post-operative. Our results suggest that removing the infarct and creating a left ventricle with homogeneous mechanical properties does not necessarily reduce the driving forces for growth and remodeling. These preliminary findings agree conceptually with clinical observations.
以心室扩张和室壁变薄为形式的心脏生长和重塑是梗死性心力衰竭的典型特征。随着时间的推移，梗死区域变硬，剩余心肌接管功能，心室变弱并扩张。目前的治疗方法试图通过切除梗死区域或为心室壁提供结构支持来减轻这些影响。然而，这些治疗方法的潜在机制尚不清楚，结果仍不尽人意。在此我们表明，心肌梗死会引起心脏形态明显的区域和透壁差异。我们引入了一个能够预测机械过载反应中结构改变的机制性生长模型。在均匀负荷下，该模型预测非均匀生长。利用这个模型，我们模拟了特定患者左心室的生长。我们比较了两种情况，术前梗死心脏的生长，以及梗死通过手术切除后同一心脏术后的生长。我们的结果表明，切除梗死区域并创建具有均匀机械特性的左心室不一定能降低生长和重塑的驱动力。这些初步发现与临床观察在概念上是一致的。
