VENTRICULAR/VASCULAR COUPLING IN THE HYPERTENSIVE RAT

高血压大鼠的心室/血管耦合

• 批准号: 2210539
• 负责人: Gary Frank Mitchell
• 金额: $ 8.6万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2210539
• 关键词: aging; antihypertensive agents; blood pressure; blood vessels; cardiac output; heart catheterization; heart ventricle; hemodynamics; hypertension; intracardiac volume; spontaneous hypertensive rat; statistics /biometry; ventricular hypertrophy

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.

高血压是心血管的绝对重要危险因素 发病率和死亡率，通过存在 左心室肥大。 尽管未经证明，但疗法成功 退化的肥大可能同时减少其相关的过剩风险。 但是，血压与左心室肿块之间的关系 很差，有效的降压治疗能力回归 心脏质量是可变的，药物特异性的，使刺激保持不变 肥大不确定。 血液动力学和左边的这种解离 心室肿块促使研究其他因素 - 交感神经系统或肾素 - 血管紧张素系统 - 可能 调节高血压的心室生长或对 降压治疗。 但是，常规分析可能会低估 血流动力学对肥厚过程的贡献。 总负载 强加在左心室上包括稳定流和脉冲 成分。 前者代表交付所需的成本 对组织的心脏输出。 后者，结果 左心室的间歇性作为泵，代表能量 需要克服惯性，弹性和反射性特征 动脉系统，通常在经典稳定流中忽略 血液动力学分析。 随着衰老和高血压，弹性元素 脉管系统由于不舒服的周期性应力而恶化 导致合规船的僵硬，可能会施加 左心室上未发现的，增加的脉冲负荷。 主动脉 输入阻抗提供了衡量左侧的总负载 脉管系统的心室。 技术的最新进展允许 小动物中主动脉输入阻抗的可靠测量。 这 当前的建议将利用主动脉输入阻抗的测量 脉搏波速度在正常和自发的高血压大鼠中 为了检验以下假设，即时间依赖性增加 左心室负荷的脉冲成分负责 衰老的“生理”心室肥大 高血压和高血压中的进行性肥大 尽管血压升高不断。 假设是 各种降压药对回归的差异作用 心室肥大涉及对脉管系统的可变作用和 因此，还将测试脉冲负荷。 首席研究员是一名受临床训练的心脏病专家 从事学术研究的职业，主要关注互动 在心室质量，功能和负载之间以及随后 心肌违规。 毕业于杨百翰和妇女医院 内科和心脏病学培训计划，他很清楚 正在开发研究人员的个人和设施 哈佛医疗区，并充分利用这一独特的机会。