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（申请人的描述逐字描述）：年龄较大与心脏发病率和死亡率明显增加有关 心肌梗塞不管溶栓疗法的给药如何 早期的侵入性方法，使用阿司匹林，ACE抑制剂和 Beta-Blockers。这些不良结果中很大一部分是相关的 梗塞本身的心脏后果，即左心室 功能障碍，心源性休克和充血性心力衰竭；尽管有 事实，梗塞大小的指标往往会随着年龄的增长而减小。这个建议 研究了与年龄相关的生理变化的广泛假设 我们先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，改变底物 心肌梗塞被叠加，以增加左的可能性 年龄较大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 表征血管负荷的模型（EA-ARTERIAL弹性）及其 与心室性能的相互作用（EES-左心室终端局力 弹性）在较老的后病后患者中，与年龄相关 心室 - 血管耦合（EA/EES关系）的变化 患者左心室功能和临床的六个月变化 结果。最后，我们建议测试减少动脉的假设 僵硬导致预期的6个月结果改善 使用L-精氨酸的随机临床试验，一种降低的药物 除了常规影响的机制以外的机制，血管负荷 侵蚀后疗法。我们预计研究结果将暗示 使用新的评估和治疗策略，这将大大 减少与年龄相关的死亡率和发病率的发病率 患者。