Strain Controlled LVAD Unloading and Post MI Remodeling

在美国，有100多万患者在心肌梗死后遭受左心室(LV)损伤。 许多人适应收缩功能的丧失和心肌梗死后的疤痕扩大，整体左心室 扩张和收缩能力降低。这种后ML过程被称为重塑。这样做的总体目标是 建议更好地了解ML后局部应变的早期局部生物力学变化是如何联系的。 到分级改建。可定义为尺寸变化或拉伸的应变增加 LV几何形状的改变。它是心肌梗死面积和心室负荷的产物。 我们将验证这样的假设，即绵羊模型中ML后10周的重塑可以通过以下方式预测 在脑梗塞后7天检测到局部应变增加。我们相信我们将能够探测到 一个面积的门槛！这将与游离壁舒张期内径增加40%相关。我们 想知道应变是如何影响心室肌兴奋性收缩偶联(ECC)和钙信号的 肌细胞。因为心肌细胞的拉伸反应包括各种细胞内的机械转导 影响Ca~(2+)处理和ECC的信号程序，我们将研究选定蛋白质的协调变化， 包括磷脂酰肌醇3‘激酶(P13K)家族。我们将独一无二地减少后m1菌株如下 应用导管微室辅助血泵重建ml应变后的阈值。减少 应变将使我们能够观察它对ML后重塑的影响以及我们所确定的分子过程。 在非调节应变条件下。这项建议将专业知识的独特组合结合在一起 完成目标所必需的。区域应变将由嵌入式晶体阵列测量，ECC将 通过来自区域单细胞分离的钙离子处理和分子分析进行评估 在区域组织和单个细胞上完成。区域细胞和组织样本的菌株历史将 为人所知。从这项工作中学到的新知识将使我们能够更好地理解这种紧张。 对重塑的反应。这些实验和方法被设计成适用于患者。我们需要 要知道心脏何时会在ML之后重塑，需要深入了解关键的分子过程 未来可能的医疗疗法。据此，我们将了解控制应变后的影响 使用微量VAD介入治疗的脑梗塞。

In the U.S. more than one million patients sustain left ventricular (LV) injury after myocardial infarction (Ml). Many adapt to the loss of contractile function and the myocardial scar by infarct expansion, global LV dilatation and reduced contractility. This post Ml process is termed remodeling. The broad goal of this proposal is to better understand how early regional biomechanical changes in regional strain after Ml relate to graded remodeling. Increased strain that may be defined as dimensional changes or stretch results from alteration of LV geometry. It is the product of infarct size and ventricular load. We will test the hypothesis that remodeling at 10weeks after Ml in an ovine model can be predicted by increases in regional strain detected at seven days following infarction. We believe we will be able to detect a threshold of area! strain that will be associated with a 40% increase in free wall diastolic dimension. We want to know how strain affects excitation contraction coupling (ECC) and Ca2+ signaling in ventricular myocytes. Because the myocyte stretch response includes mechanotransduction of various intracellular signaling programs that affect Ca2+ handling and ECC, we will study coordinate changes in select proteins, including the phosphoinositide 3' kinase (P13K) family. We uniquely will reduce post Ml strain below threshold for remodeling post Ml strain by catheter based micro ventricular assist blood pump. Reduction of strain will permit us to observe its effect on post Ml remodeling and the molecular processes we determined in the unregulated strain condition. This proposal brings together the unique combination of expertise required to complete the aims. Regional strain will be measured by embedded crystal array, ECC will be evaluated by Ca2+ handling derived from regional single cell isolates, and molecular analysiswill be completed on regional tissue and single cells. The strain history of the regional cell and tissue samples will be known. New knowledge from this work will permit us to have a greater appreciation of the strain-stretch response on remodeling. The experiments and methods are designed to be translated to patients. We need to know when hearts will remodel after Ml and need to gain insight into critical molecular processes for possible future medical therapies. Accordingly, we will learn the impact of controlled strain after large infarction with an interventionally applied micro VAD.