DIASTOLIC FILLING DYNAMICS OF EXERCISE AND HEART FAILURE

左心室舒张期特性的临床意义 (LV)已得到越来越多的认可。常见心脏疾病患者 高血压、左心室肥厚或缺血等疾病可能会 充血性心力衰竭(CHF)，尽管左心室收缩功能正常，由于 左心室舒张期充盈受损。这导致了对 正常左心室舒张期充盈的决定因素。然而，它的作用机制 运动或心力衰竭发展对左室舒张功能的影响 性能尚未得到调查。 在运动中，心输出量的增加主要是由于 心率。心动过速缩短了舒张期，提供了 较短的左心室舒张期充盈时间。因此，二尖瓣的速度 运动时，瓣膜流量(和左心室充盈率)必须显著增加。 以保持或增加冲程音量。快速发展的机制 左心室舒张期充盈是在剧烈运动过程中产生的 为人所知。此外，心力衰竭对早期舒张期充盈的影响 在运动期间还没有被调查。 本课题将定量评价左心室舒张期的作用机制。 在运动期间，在心脏发育期间，补充清醒的狗 失败(CHF)，以及在CHF后的运动中。我们将测试四个 假设。假设1.运动过程中，LV舒张期早期的比率 充盈是通过增加心肌松弛速率和 收缩末期容量下降。这导致早期的 舒张期左心室压(P)，增加二尖瓣舒张期早期 左心房(LA)内压无增加的梯度。 压力-体积关系不变。假设2.在慢性病中， 心动过速所致心力衰竭时，心肌松弛速度减慢， 左心室舒张末压力-容量向上移动。 两性关系。二尖瓣舒张期早期压差对左心室舒张期的影响 填充物是通过提升大腿高度来产生的。假说3.关于 运动时的舒张压在充血性心力衰竭后改变。有了CHF， 在运动和运动中，心肌松弛和左心室排空没有增强 早期舒张期左室压升高。LV率的任何增加 充血性心力衰竭后的舒张期运动是由于LAP增加所致。 假设4.运动引起的左房压力增加 使用正性肌力调节剂治疗可以减少CHF的发生 一种血管紧张素转换酶抑制剂。 这些研究将在有意识的狗身上进行，长期使用仪器 测量LVP、LAP和LV容量。这些研究将提供重要的 关于LV舒张期内翻的机制的新信息 正常运动和充血性心力衰竭后运动。这些研究是必要的，以 扩大我们对正常动物静息状态下舒张期LV内径的了解 对常见的生理应激和病理条件。这可能会导致 改善慢性心力衰竭患者运动耐量的新策略。

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.