HYPERTENSION AND HYPERTROPHY IN THE NON-HUMAN PRIMATE

这项研究提案的主要目标是定义基本的 左心室的力学、神经和生化特性 一种独特的压力超负荷肥厚和肥厚消退模型 非人灵长类动物实验性肾性高血压的研究 (巴布亚，帕皮奥·阿努比斯)我们的工作假设是纵向的 应用收缩末期应力-体积研究心脏收缩功能， 应用应力-长度、应力-速度关系和舒张期功能 室腔和心肌硬度的定量将确定 哪些左心功能特征预示着心力衰竭的发生 宫缩性抑郁症。使用这种方法，我们建议测试 以下是具体的假设：1)心肌收缩抑制 在压力超负荷时，肥厚表现为向右平行 左心力-长度斜率的移动和/或凹陷 关系。2)左心室重量与心脏重量比值的降低 体积或厚度与尺寸之比将是收缩的早期标志 抑郁症。3)在压力超负荷时增加心肌硬度 与室壁僵硬不同的是，如果没有 心肌胶原蛋白含量增加。4)肥大的消退 会伴随着收缩功能不变，心腔缩小 硬度和对心肌硬度的不同影响。5) 高血压患者肥厚程度的异质性 相似的严重程度和持续时间可能与 肾素-血管紧张素和血管紧张素转换酶对肥大过程的调控 交感神经系统。6)灵长类动物肌球蛋白ATPase的变化 活性和/或同工酶图谱将是早期和敏感的标志 宫缩性抑郁症。以下具体研究旨在 回答这些假设：患有慢性高血压(2-4岁)的狒狒 在此期间将研究左室肥厚和可变收缩功能。 肥厚进展和肥厚消退期间所产生的 甲基多巴。系列双平面LV电影/M型超声心动图 将使用高保真压力测量来评估系列 收缩末期周向/经线的改变 应力-体积/尺寸关系和舒张期特性。血浆肾素， 儿茶酚胺和加压素水平加上压力感受器功能 在有意识的状态下测量。心肌组织羟脯氨酸和 肌球蛋白ATPase将在尸检时进行检测。这是意料之中的 多学科方法将提供对 压力超负荷演变和回归的决定因素 与人类亲缘关系相近的动物模型中的肥大。

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.