MECHANISMS OF SYSTOLIC AND DIASTOLIC CARDIAC DEFORMATION

心壁心肌纤维的斜向螺旋形成一个 卓越的机械系统，旨在放大少量的 心肌缩短为广泛增厚，然后迅速回缩， 允许突然快速填充。 通过这项提议，我们继续我们的 使用MRI组织标记的LV壁变形研究。 这个强大 新的成像技术，在我们的实验室开发，现在广泛使用， 允许通过心动周期对组织进行无创跟踪， 和变形的测量。 以前的标记工作表明， 心脏的扭动运动或扭转的重要性， 收缩和舒张功能。 人类的正常衰老伴随着急剧和渐进的衰退 左心室舒张早期充盈率的变化。 这使老年人 充血性心力衰竭，给老年人带来了巨大的负担， 在发病率和死亡率方面， 社会的成本。 本项目的目标是探索 老年舒张功能障碍的机制，以及减缓其 进展 提出了四个项目。 第一，反冲率 扭转似乎是一个有价值的新的非侵入性标记的过程 LV松弛 与标准的非侵入性参数相反， 等容舒张时间、回缩率与主动脉和 左心房压力，因此可能是一个上级指标。 这 假设将建立在实验模型上。 二是 认为松弛通过产生吸力而有助于填充， 这增加了左心房的流入量。 新证据表明 在年轻的时候，放松和充实实际上是紧密相连的。 然而，在老年人中，填充似乎与 松弛，可能是由于刚度增加。 也就是说， 心脏可能不会产生吸力，使充盈取决于LA 驱动压力。 松弛和充盈之间的关系如下： 在不同年龄段的正常人中进行了核磁共振成像测试。 第三、 将在相同群体中测量收缩期纤维缩短。 和 最后，由于血管紧张素转换酶抑制剂和血管紧张素 受体阻滞剂抑制纤维化，这有助于心脏 僵硬，他们对舒张功能障碍的影响，老化将是 在大鼠模型中研究。 这一结果将有助于阐明增龄性舒张功能障碍的机制。 功能障碍，并将提高我们对衰老如何相互作用的理解 影响老年人心力衰竭的病程。 这可能会导致合理的新疗法的发展。

The oblique spirals of myocardial fibers in the heart wall form a remarkable mechanical system, designed to amplify small amounts of myocardial shortening into extensive thickening, then to recoil briskly, allowing sudden, rapid filling. With this proposal we continue our studies of LV wall deformation using MRI tissue tagging. This powerful new imaging technique, developed in our laboratory and now widely used, permits the non-invasive tracking of tissue through the cardiac cycle, and measurement of deformation. Previous work with tagging has shown the importance of the heart's wringing motion, or torsion , for systolic and diastolic function. Normal aging in humans is accompanied by a sharp and progressive decline in the rate of LV early diastolic filling. This predisposes the elderly to congestive heart failure, presenting a large burden to the aging population in terms of morbidity and mortality, and enormous medical costs to society. The objective of this project is to explore the mechanisms of diastolic dysfunction of aging, and ways to slow its progression. Four projects are proposed. First, the rate of recoil of torsion seems to be a valuable new non-invasive marker of the process of LV relaxation. As opposed to the standard non-invasive parameter, isovolumic relaxation time, recoil rate is independent of aortic and left atrial pressures, and may therefore be a superior index. This hypothesis will be rested in an experimental model. Second, it is thought that relaxation contributes to filling by generating suction, which augments inflow from the left atrium. New evidence suggests that in the young, relaxation and filling are, in fact, tightly coupled. However, in the elderly, filling seems to become uncoupled from relaxation, perhaps due to increased stiffness. That is, the aging heart may not generate suction, leaving filling dependent upon the LA driving pressure. The relation between relaxation and filling will be tested using MRI in normal humans over a wide range of ages. Third, systolic fiber shortening will be measured in the same population. And finally, since angiotensin converting enzymes inhibitors and angiotensin receptor blockers inhibit fibrosis, which contributes to heart stiffness, their effect on the diastolic dysfunction of aging will be studied in a rat model. The results will help clarify the mechanisms of age-induced diastolic dysfunction, and will improve our understanding of how aging interacts with disease to influence the course of heart failure in the elderly. This may lead to the development of rational new therapies.