VENTRICULAR/VASCULAR COUPLING IN THE HYPERTENSIVE RAT.

高血压是心血管疾病的一个明确的重要危险因素， 发病率和死亡率之间的关联， 左心室肥大 虽然没有得到证实，但治疗成功， 消退性肥大可同时降低其相关的过度风险。 然而，血压和左心室质量之间的关系 是穷人和有效的抗高血压治疗的能力倒退 心脏质量是可变的，并且是药物特异性的， 肥大不确定。 血液动力学和左心室 心室质量促使研究其他因素- 交感神经系统或肾素-血管紧张素系统， 调节高血压心室生长或对 抗高血压治疗 然而，传统分析可能低估了 血液动力学对肥大过程的影响。 总负载 施加在左心室上的血流包括稳态血流和脉动血流 件. 前者是提供所需服务的费用， 心脏输出到组织。 后者，一个后果， 左心室作为泵的间歇性性质，代表能量 需要克服的惯性，弹性和反射特性， 动脉系统，在经典的稳态流中通常被忽略 血流动力学分析。 随着年龄的增长和高血压， 血管系统的退化是对持续的周期性压力的反应 导致顺应性容器变硬 左心室未被发现的脉动负荷增加 主动脉 输入阻抗提供了放置在左侧的总负载的度量 由脉管系统控制心室。 最近的技术进步允许 小动物主动脉输入阻抗的可靠测量。 的 目前的提议将利用主动脉输入阻抗的测量， 正常血压和自发性高血压大鼠的脉搏波速度 为了检验这一假设， 左心室负荷的脉动分量负责 “生理性”心室肥大的老化，在缺乏 高血压和高血压中观察到的进行性肥大 尽管血压持续升高 的假设 各种抗高血压药物对消退的差异作用 心室肥大涉及对脉管系统的可变影响， 因此也将测试脉动负载。 主要研究者是一名经过临床培训的心脏病专家， 从事学术研究，主要关注 高血压患者心室质量、功能和负荷与 心肌梗塞 布里格姆妇女医院毕业 在内科和心脏病学的培训计划，他很清楚， 个人和设施提供给一个发展中的研究人员在 哈佛医学区，并充分利用这一独特的机会。

Hypertension is an unequivocally important risk factor for cardiovascular morbidity and mortality, an association strengthened by the presence of left ventricular hypertrophy. Though not proven, therapy successful in regressing hypertrophy may concurrently reduce its associated excess risk. However, the relationship between blood pressure and left ventricular mass is poor and the ability of effective antihypertensive therapy to regress cardiac mass is variable and drug-specific, leaving the stimulus to hypertrophy uncertain. this dissociation between hemodynamics and left ventricular mass has prompted investigation of additional factors - the sympathetic nervous system or the renin-angiotensin system - that may modulate ventricular growth in hypertension or in response to antihypertensive therapy. However, conventional analyses may underestimate the hemodynamic contribution to the hypertrophic process. The total load imposed on the left ventricle includes both steady-flow and pulsatile components. The former represents the cost of delivering the required cardiac output to the tissues. The latter, a consequence of the intermittent nature of the left ventricle as a pump, represents energy needed to overcome the inertial, elastic and reflective characteristics of the arterial system and is generally ignored in classic steady-flow hemodynamic analyses. With aging and in hypertension, the elastic elements of the vasculature deteriorate in response to unremitting cyclical stresses resulting in stiffening of the compliance vessels which may thereby impose an undetected, increased pulsatile load on the left ventricle. Aortic input impedance provides a measure of the total load placed on the left ventricle by the vasculature. Recent advances in technology allow for reliable measurement of aortic input impedance in small animals. The current proposal will utilize measurement of aortic input impedance and pulse wave velocity in normotensive and spontaneously hypertensive rats in order to test the hypothesis that a time-dependent increase in the pulsatile component of left ventricular load is responsible for the "physiologic" ventricular hypertrophy of aging in the absence of hypertension and for the progressive hypertrophy seen in hypertension despite a constant level of blood pressure elevation. The hypothesis that the differential effect of various antihypertensive agents on regression of ventricular hypertrophy relates to a variable effect on the vasculature and thereby on pulsatile load will also be tested. The principal investigator is a clinically-trained cardiologist committed to a career in academic research with a primary focus on the interaction between ventricular mass, function and load in hypertension and following myocardial infraction. A graduate of the Brigham and Women's Hospital training programs in Internal Medicine and Cardiology, he is well aware of the individuals and facilities available to a developing researcher in the Harvard medical area and takes full advantage of this unique opportunity.