VENTRICULAR/VASCULAR COUPLING IN THE HYPERTENSIVE RAT

高血压无疑是心血管疾病的重要危险因素。 发病率和死亡率，这一联系因 左心室肥厚。虽然没有得到证实，但治疗在 消退性肥厚可能同时降低其相关的额外风险。 然而，血压与左心室重量之间的关系 降压治疗效果差且能力减退 心脏质量是可变的和药物特有的，将刺激留给 肥大不确定。血流动力学和左脑的这种分离 心室质量促使对其他因素的调查- 交感神经系统或肾素-血管紧张素系统-可能 调节高血压或高血压患者的脑室发育 抗高血压治疗。然而，传统的分析可能低估了 血流动力学对肥大过程的贡献。总负荷 对左心室施加的压力包括稳定期和搏动性 组件。前者代表交付所需服务的成本 心输出量对组织的影响。后者，是 作为泵的左心室的间歇性特征，代表能量 需要克服惯性、弹性和反射特性 动脉系统，在经典的恒定流中通常被忽略 血液动力学分析。随着年龄的增长和高血压，弹性元素 血管系统因持续的周期性应激而恶化 从而导致顺应性容器的硬化，从而可施加 一种未被察觉的、增加的左心室搏动性负荷。主动脉 输入阻抗提供对放置在左侧的总负载的测量 脑室通过血管系统。最近的技术进步使我们能够 小动物主动脉输入阻抗的可靠测量。这个 目前的提议将利用测量主动脉输入阻抗和 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，随着时间的推移， 左心室负荷的搏动性成分是导致 “生理性”增龄性心肌肥厚 高血压和高血压所见的进行性肥厚 尽管血压持续升高。假设 不同降压药对高血压消退的不同影响 心室肥厚与血管系统的不同影响有关， 从而也将对脉动负载进行测试。 首席研究员是一位受过临床训练的心脏病专家。 把主要精力放在互动的学术研究上 高血压患者及以下患者的心脏重量、功能和负荷之间的关系 心肌梗死。毕业于布里格姆妇女医院 内科和心脏病学的培训计划，他很清楚 可供发展中国家的研究人员使用的个人和设施 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.