VENTRICULAR/VASCULAR COUPLING OF THE DEVELOPING CARDIOVASCULAR SYSTEM

在组织水平上，心功能的生物力学调节是 发展中的心血管系统的基本特性。这 在狭窄的操作范围内，组织水平调节是显而易见的 控制心率、发展压和中风等参数 在正常发育期间的体积(Clark 1990a)，以及 胚胎心脏调节质量以适应工作量(Clark 1989a)。尽管 能够定义胚胎循环的运行范围，我们 还没有确定决定 心血管形态和功能之间的相互作用。值得注意的是，以前的 设计和分析了关于单个心脏的实验 元素。目前对成熟循环的研究支持 将心血管系统定义为闭合环路，其中 电路的每个元件的输入、功能和输出是 定义和相关(Sunagawa 1984，Sagawa 1988a)。这个闭环系统 框架允许定义心血管调节。 我们的长期目标是确定组织水平的调节机制 在胚胎心血管系统之间产生动态的相互依赖 功能和形态。我们假设血液动力学和机械性 脑室和血管床之间的耦合优化功能和 影响形态发生。我们的实验模型是第16至24阶段 白色来航鸡在脑室几何构型转变过程中的发育 从光滑的墙体到骨小梁室。我们的实验方法 都在生理学核心中描述，并包括同时 测量心室压、腹主动脉背压和 流和视频成像。 我们在这个项目中的具体目标是首先定义 胎心急性期脑室和动脉床的变化 心率和激活顺序、前负荷和血管张力 正常发育。然后我们定义了胚胎之间的相互作用 脑室和动脉床对心率的变化，激活 生长加速后的顺序、预负荷和血管张力 由圆锥主干条带产生，生长减速产生 部分左房结扎。 这个项目定义了胚胎的功能相互作用 脑室和动脉床在各种急慢性疾病期间 血流动力学性能的改变。对实验数据的分析 闭环系统框架内的结果提供了至关重要的 关于心血管功能调节的信息。这 于是，综合分析就成为了结构和 遗传性心血管系统的功能分析 实验模型，并最终帮助定义潜在的 先天性心血管畸形的病因。

Tissue level, biomechanical regulation of cardiac function is a fundamental property of the developing cardiovascular system. This tissue level regulation is evident in the narrow operating range of control parameters such as heart rate, developed pressure, and stroke volume during normal development (Clark 1990a), and the ability of the embryonic heart to adjust mass to workload (Clark 1989a). Despite the ability to define the operating range of the embryonic circulation, we have not yet identified the fundamental mechanisms which determine the interaction between cardiovascular form and function. Of note, previous experiments were designed and analyzed with respect to a single cardiac element. Current research in the mature circulation supports the definition of the cardiovascular system as a closed loop, where the input, function, and output of each of the elements of the circuit are defined and related (Sunagawa 1984, Sagawa 1988a). This closed-loop framework allows the definition of cardiovascular regulation. Our long term aim is to define the tissue level regulatory mechanisms that produce the dynamic interdependence between embryonic cardiovascular function and morphology. We hypothesize that hemodynamic and mechanical coupling between the ventricle and vascular bed optimize function and influences morphogenesis. Our experimental models is the stage 16 to 24 white Leghorn chick embryo during the transition of ventricular geometry from a smoothwalled to a trabecular chamber. Our experimental methods are described in the Physiology Core, and include the simultaneous measurement of ventricular pressure, dorsal aortic pressure and flow, and video imaging. Our specific aims in this project are to first define the interaction of the embryonic ventricle and arterial bed during acute changes in the heart rate and activation sequence, preload, and vascular tone during normal development. We then define the interaction of the embryonic ventricle and arterial bed to changes in the heart rate, activation sequence, preload, and vascular tone following growth acceleration produced by conotruncal banding and growth deceleration produced by partial left atrial ligation. This project defines the functional interaction of the embryonic ventricle and arterial bed during wide range of acute and chronic alterations in hemodynamic performance. The analysis of experimental results within the framework of a closed loop system provides crucial information on the regulation of cardiovascular function. This integrated analysis then becomes the foundation for the structural and functional analysis of genetically altered cardiovascular systems in experimental models, and ultimately, aids in defining the underlying etiologies of congenital cardiovascular malformations.