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MECHANISMS OF SYSTOLIC AND DIASTOLIC CARDIAC DEFORMATION

收缩期和舒张期心脏变形的机制

基本信息

批准号：
6389165
负责人：
EDWARD P SHAPIRO
金额：
$ 28.32万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-02-27 至 2003-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6389165
关键词：
age difference aging clinical research dogs echocardiography heart contraction heart dimension /size heart failure heart function heart motion heart pharmacology heart ventricle human subject intracardiac pressure intracardiac volume laboratory rat magnetic resonance imaging

项目摘要

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.

心肌壁中的心肌纤维斜行形成一种非凡的机械系统，旨在放大少量的心肌缩短为广泛性增厚，然后迅速回缩，允许突然、快速地填充。有了这项提议，我们将继续我们的磁共振组织标记法研究左室壁变形。这个强大的我们实验室开发并广泛使用的新成像技术，允许在整个心脏周期中对组织进行非侵入性跟踪，和变形的测量。以前使用标记的工作已经显示心脏剧烈运动或扭转的重要性收缩和舒张期功能。人类的正常衰老伴随着急剧的渐进性衰退。左室舒张早期充盈率。这使老年人有先入为主的倾向到充血性心力衰竭，给老年人带来很大的负担在发病率和死亡率方面的人口，以及巨大的医疗给社会带来的代价。这个项目的目标是探索增龄性舒张期功能障碍的机制及延缓其发生的途径进步。提出了四个项目。首先，后座力的速度扭转似乎是一个有价值的新的非侵入性标志。 LV松弛。与标准非侵入性参数相反，等容松弛时间、反弹率独立于主动脉和左房压力，因此可能是一个更好的指标。这假设将建立在一个实验模型上。第二，它是认为放松通过产生吸力来促进充盈，这增加了从左心房流入的流量。新的证据表明在年轻人身上，放松和充实实际上是紧密相连的。然而，在老年人中，填充物似乎变得与放松，可能是因为僵硬程度增加了。也就是老龄化心脏可能不会产生吸力，使充盈取决于左房驾驶压力。松弛和填充之间的关系将是在不同年龄段的正常人身上进行了核磁共振测试。第三, 将在同一人群中测量收缩纤维缩短。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导致心脏的纤维化僵硬，它们对衰老的舒张性功能障碍的影响将是在老鼠模型上进行了研究。这些结果将有助于阐明年龄诱导的舒张期的机制。功能障碍，并将提高我们对衰老如何相互作用的理解疾病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。