VASCULAR INTERACTION WITH AGE IN MYOCARDIAL INFARCTION

心肌梗塞中血管与年龄的相互作用

• 批准号: 6789926
• 负责人: Steven Paul Schulman
• 金额: $ 38.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-10 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789926
• 关键词: age difference; arginine; clinical trials; elasticity; heart circulation; heart disorder chemotherapy; heart function; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; myocardial infarct sizing; myocardial infarction; patient oriented research; prognosis; vascular resistance

DESCRIPTION (the applicant's description verbatim): Older age is associated with a marked increase in cardiac morbidity and mortality following a myocardial infarction regardless of the administration of thrombolytic therapy, an early invasive approach, and the use of aspirin, ACE-inhibitors and beta-blockers. A significant proportion of these adverse outcomes are related to the cardiac consequences of the infarct itself, namely left ventricular dysfunction, cardiogenic shock, and congestive heart failure; in spite of the fact that indices of infarct size tend to decrease with age. This proposal examines the broad hypothesis that the age-associated physiologic changes in vascular and ventricular properties we previously studied and described, and most importantly increased stiffness, alter the substrate upon which a myocardial infarction is superimposed so as to increase the likelihood of left ventricular dysfunction, and clinical congestive heart failure in older patients. More specifically, we propose to use sophisticated techniques and models to characterize vascular load (Ea-arterial elastance) and its interaction with ventricular performance (Ees- left ventricular end-systolic elastance) in older post-infarction patients and to relate age-associated changes in ventricular-vascular coupling (Ea/Ees relationship) in these patients to six-month changes in left ventricular function and to clinical outcomes. Finally, we propose to test the hypothesis that decreasing arterial stiffness results in an improvement in 6-month outcomes in a prospective, randomized clinical trial employing L-arginine, an agent that decreases vascular load via mechanisms other than those influenced by routine post-infarction therapies. We anticipate that the study findings will suggest the use of new evaluation and therapeutic strategies, which will significantly decrease the age associated mortality and morbidity in post-infarction patients.

描述（申请人的逐字描述）：年龄较大与心脏病发病率和死亡率显着增加有关。 无论是否进行溶栓治疗，都会发生心肌梗塞， 早期侵入性方法，以及使用阿司匹林、ACE 抑制剂和 β-受体阻滞剂。这些不良后果中有很大一部分与 梗塞本身对心脏的影响，即左心室 功能障碍、心源性休克和充血性心力衰竭；尽管 事实上，梗塞面积指数往往随着年龄的增长而减小。这个提议 检验了一个广泛的假设，即与年龄相关的生理变化 我们之前研究和描述的血管和心室特性，以及 最重要的是增加刚度，改变基材 心肌梗塞叠加，从而增加左心梗塞的可能性 老年人的心室功能障碍和临床充血性心力衰竭 患者。更具体地说，我们建议使用复杂的技术和 表征血管负荷（Ea-动脉弹性）的模型及其 与心室性能的相互作用（Ees-左心室收缩末期 弹性）在老年梗死后患者中并与年龄相关 心室-血管耦合（Ea/Ees 关系）的变化 患者左心室功能六个月的变化和临床 结果。最后，我们建议检验动脉血流量减少的假设 僵化导致 6 个月结果的预期改善， 使用 L-精氨酸（一种可降低 通过常规影响以外的机制来调节血管负荷 梗塞后治疗。我们预计研究结果将表明 使用新的评估和治疗策略，这将显着 降低梗死后与年龄相关的死亡率和发病率 患者。