HYPERTENSION AND HYPERTROPHY IN THE NON-HUMAN PRIMATE

这项研究的主要目的是确定基本的 左心室的力学、神经肱骨和生化特性 压力超负荷肥大和肥大消退的独特模型 实验诱导的非人灵长类动物肾性高血压 （狒狒，Papio anubis）。 我们的工作假设是 使用收缩末期应力-容积的收缩功能研究， 应力-长度和应力-速度关系以及舒张功能 心室腔和心肌硬度的定量将确定 左心室功能的特征预示着 收缩性抑郁 使用这种方法，我们建议测试 以下具体假设：1）心肌收缩抑制 在压力超负荷性肥大中， 左心室力-长度斜率的偏移和/或降低 关系。 2)左心室质量与心肌重量比值的降低 体积或厚度尺寸将是收缩的早期标志物， 萧条 3)这增加了压力超负荷时的心肌硬度 不像腔室僵硬的肥大不会在没有 增加心肌胶原含量。 4)肥大的消退 将伴随着收缩功能不变， 硬度和对心肌硬度的可变影响。 5)的 高血压反应性肥大程度的异质性 相似的严重程度和持续时间可能与 通过肾素-血管紧张素调节肥大过程， 交感神经系统 6)灵长类动物肌球蛋白ATP酶的改变 活性和/或同工酶模式将是一个早期和敏感的标志， 收缩性抑郁 以下具体研究旨在 回答这些假设：慢性高血压（2 - 4年）狒狒与 将在研究期间研究LV肥大和可变收缩功能。 肥大的进展和在肥大消退期间， 甲基多巴 连续双平面左室电影血管造影/M型超声心动图， 高保真度压力测量将用于评估系列 收缩末期环周/冠状动脉改变 应力-容积/尺寸关系和舒张特性。 血浆肾素， 儿茶酚胺和加压素水平加上压力感受器功能将 在意识状态下测量。 心肌组织羟脯氨酸和 将在尸检时测定肌球蛋白ATP酶。 预计， 多学科的方法将提供基本的见解， 压力超负荷发展和消退的决定因素 肥大的动物模型，在遗传学上接近人类。

The major objective of this research proposal is to define the fundamental mechanical, neurohumeral and biochemical properties of left ventricular pressure overload hypertrophy and hypertrophy regression in a unique model of experimentally induced renal hypertension in the nonhuman primate (baboon, papio anubis). Our working hypothesis is that longitudinal studies of systolic function using end systolic stress-volume, stress-length and stress-velocity relations and of diastolic function using quantitation of ventricular chamber and myocardial stiffness will identify which characteristics of left ventricular performance herald the onset of contractile depression. Using this approach, we propose to test the following specific hypotheses: 1) That myocardial contractile depression in pressure overload hypertrophy is manifest by either a rightward parallel shift and/or a depression in the slope of the left ventricular force-length relation. 2) That a decrease in the ratio of left ventricular mass to volume or thickness to dimension will be an early marker for contractile depression. 3) That augmented myocardial stiffness in pressure overload hypertrophy unlike chamber stiffness will not occur in the absence of increased myocardial collagen content. 4) That regression of hypertrophy will be accompanied by unaltered contractile function, reduced chamber stiffness and variable effects upon myocardial stiffness. 5) That heterogeneity in the magnitude of hypertrophy in response to hypertension of similar severity and duration may relate to differences in the modulation of the hypertrophy process by the renin-angiotensin and sympathetic nervous systems. 6) That alterations in primate myosin ATPase activity and/or isoenzyme patterns will be an early and sensitive marker of contractile depression. The following specific studies are designed to answer these hypotheses: chronically hypertensive (2-4 years) baboons with LV hypertrophy and variable systolic function will be studied during the progression of hypertrophy and during hypertrophy regression produced by methyldopa. Serial biplane LV cineangiography/M-mode echocardiography with high fidelity pressure measurement will be used to assess serial alterations in end-systolic circumferential/meridional stress-volume/dimension relations and diastolic properties. Plasma renin, catecholamines and vasopressin levels plus baroreceptor function will be measured in the conscious state. Myocardial tissue hydroxyprolene and myosin ATPase will be assayed at necropsy. It is anticipated this multidisciplinary approach will provide basic insights into the determinants of the evolution and regression of pressure overload hypertrophy in an animal model phylogenetically close to man.