DIASTOLIC FILLING DYNAMICS OF EXERCISE AND HEART FAILURE

运动和心力衰竭的舒张期充盈动力学

• 批准号: 3473276
• 负责人: CHE-PING CHENG
• 金额: $ 9.68万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473276
• 关键词: ACE inhibitors; cardiac output; cardiovascular pharmacology; congestive heart failure; dogs; exercise; heart contraction; hemodynamics; intracardiac pressure; intracardiac volume; muscle stimulant; ouabain; tachycardia; vasodilators

The clinical importance of the diastolic properties of the left ventricle (LV) have been increasingly recognized. Patients with common cardiac diseases such as hypertension, LV hypertrophy, or ischemia may have congestive heart failure (CHF), despite normal LV systolic function, due to impaired diastolic LV filling. This has led to investigation of the determinants of normal LV diastolic filling. However, the mechanisms of the effects of exercise or the development of heart failure on LV diastolic performance have not been investigated. During exercise, cardiac output rises primarily due to a marked increase in heart rate. The tachycardia decreases the duration of diastole, providing less time for diastolic filling of the LV. Thus, the velocity of mitral valve flow (and rate of LV filling) must markedly increase during exercise to maintain or increase the stroke volume. The mechanism by which rapid diastolic filling of the LV is produced during vigorous exercise is not known. Further, the effect of heart failure on the early diastolic filling during exercise has not been investigated. This project will quantitatively evaluate the mechanism of LV diastolic filling in conscious dogs during exercise, during the development of heart failure (CHF), and during exercise after CHF. We will test four hypotheses. Hypothesis 1. During exercise, the rate of LV early diastolic filling is augmented by an increased rate of myocardial relaxation and a fall in end-systolic volume. This results in a reduction of early diastolic LV pressure (P), increasing the early diastolic mitral valve gradient without an increase in left atrial (LA) P. The LV end-diastolic pressure-volume relation is unaltered. Hypothesis 2. In chronic, tachycardia-induced CHF, the rate of myocardial relaxation is reduced and there is an upward shift of the LV end-diastolic pressure-volume relationship. The early diastolic mitral valve gradient for LV diastolic filling is produced by an elevation of LAP. Hypothesis 3. The dynamics of diastolic filing during exercise are altered after CHF. With CHF, myocardial relaxation and LV emptying are not enhanced during exercise and early diastolic LV pressure is elevated. Any increase in the rate of LV diastolic filing with exercise after CHF results from an increase in LAP. Hypothesis 4. The exercise induced increase in left atrial pressure occurring in CHF can be diminished by treatment with a positive inotrope or an angiotensin converting enzyme inhibitor. These studies will be performed in conscious dogs, chronically instrumented to measure LVP, LAP, and LV volume. These studies will provide important new information concerning the mechanism of LV diastolic filing during normal exercise and exercise after CHF. These studies are necessary to extend our knowledge of the diastolic LV filing in normal animals at rest to common physiologic stress and pathologic conditions. This may lead to new strategies to improve exercise tolerance in CHF.

左室舒张特性的临床意义 (LV)已经越来越被认可。 常见心脏病患者 高血压、左心室肥大或局部缺血等疾病可能 充血性心力衰竭（CHF），尽管LV收缩功能正常，由于 舒张期LV充盈受损。 这导致了对 正常左室舒张期充盈的决定因素。 然而， 运动或心力衰竭对左室舒张功能的影响 性能没有被调查。 在运动过程中，心输出量增加主要是由于 心率 心动过速缩短了心动过速的持续时间， 左心室舒张期充盈时间缩短。 因此，二尖瓣血流速度 瓣膜流量（和LV充盈率）必须在运动期间显著增加 以维持或增加每搏输出量。 这种机制， 左心室舒张期充盈是在剧烈运动时产生的， 知道的 此外，心力衰竭对舒张早期充盈的影响 在运动中没有被调查。 本课题将定量评价左室舒张功能的机制， 在运动过程中，在心脏发育过程中， 心力衰竭（CHF）和CHF后运动期间。 我们将测试四个 假设 假设1. 运动时，左室舒张早期 充盈通过增加心肌舒张速率和 收缩末期容积下降。 这导致了早期 左室舒张压（P），舒张早期二尖瓣增加 左心房（LA）P没有增加。LV舒张末期 压力-体积关系不变。 假设2. 在慢性， 心动过速诱导的CHF，心肌舒张速率降低， 左室舒张末期压力-容积向上移动 关系 左室舒张早期二尖瓣跨瓣压差 填充是通过升高0.05来产生的。 假设3. 的动态 运动时舒张压的充盈在CHF后改变。 对于CHF， 在运动过程中心肌舒张和LV排空没有增强， 左心室舒张早期压升高。 LV发生率的任何增加 充血性心力衰竭后运动时舒张期充盈是由于舒张压增加所致。 假设4. 运动引起左心房压力升高 可通过使用正性肌力药治疗或 血管紧张素转化酶抑制剂。 这些研究将在清醒的犬中进行， 测量LVP、LV和LV容量。 这些研究将提供重要的 关于左室舒张期充盈机制的新信息， 正常运动和CHF后运动。 这些研究对于 扩展了我们对正常动物静息时舒张期LV充盈的了解 常见的生理压力和病理条件。 这可能导致 提高CHF患者运动耐量的新策略。