Autonomic regulation of coronary blood flow in superior and inferior sinoatrial node

上下窦房结冠脉血流的自主调节

• 批准号: 10822027
• 负责人: Nathan Grainger
• 金额: $ 21.32万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-03-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822027
• 关键词: Affect; Arteries; Blood; Blood Vessels; Blood flow; Cardiac; Cardiac Myocytes; Cardiovascular system; Centers of Research Excellence; Circulation; Clinical; Coronary; Coronary artery; Coupling; Disease; Endothelial Cells; Event; Exercise; Exhibits; Future; Goals; Heart; Heart Atrium; Heart failure; Inferior; Lung; Mediating; Molecular; Mus; Nerve; Nevada; Nodal; Pathway interactions; Patients; Pattern; Perfusion; Pericytes; Periodicity; Physiological; Pump; Regulation; Rest; Signal Transduction; Sinoatrial Node; Smooth Muscle Myocytes; Sympathetic Nervous System; Vascular Smooth Muscle; Vascular resistance; atrioventricular node; cell type; density; response; spatial relationship

The sinoatrial node is the origin of organized and rhythmic electrical depolarizations in the heart. After leaving the sinoatrial node, depolarizations spread throughout the atrium and ventricles via the atrioventricular node and specialized conduction pathways to initiate excitation-contraction coupling of cardiomyocytes. This highly organized pattern of events is critical for blood to be pumped throughout the pulmonary and systemic circulations. Therefore, the sinoatrial node is critical for the initiation of each cardiac cycle. To sustain the constant diastolic spontaneous depolarizations in the sinoatrial node, blood is delivered to the node via the right coronary artery. Although many groups have investigated the mechanisms responsible for nodal pacemaking, we continue to have a very limited understanding of how blood flow is regulated in the sinoatrial node during either resting or elevated physiological conditions (i.e., exercise). Adequate perfusion of the node is critical since clinical evidence suggests that damage or blockage of the sinoatrial nodal artery is pro-arrhythmogenic. Previous studies indicate that there are differences in microvascular density between the superior and inferior regions of the sinoatrial node, however the significance of this is unclear. Furthermore, during heart failure, patients exhibit deficits in normal sinoatrial node function and reductions in coronary vascular density. The overarching goal of this project is to determine how blood flow is regulated during sympathetic nervous system activation and how this regulation is affected during disease such as heart failure. First, we plan to investigate the spatial relationship between sympathetic nerves and cell types involved in mediating vascular resistance (i.e., vascular smooth muscle cells, endothelial cells and pericytes) to determine where the effects of sympathetic activation are mediated. Next, we will isolate microvasculature from the sinoatrial node and elucidate the effect of sympathetic activation to determine whether the superior and inferior sinoatrial node artery responds differentially to nerve activation. Lastly, we will investigate how heart failure in the mouse causes changes in the microvascular density and response to sympathetic stimulation. This project will serve as a basis for future studies by dissecting the key components of blood flow regulation in the sinoatrial node.

窦房结是心脏中有组织和有节奏的电去极化的起源。后 离开窦房结后，去极化通过房室传导途径扩散到整个心房和心室。 节点和专门的传导途径，以启动兴奋-收缩耦合 心肌细胞这种高度组织化的事件模式对于血液在整个组织中泵送至关重要。 肺循环和体循环。因此，窦房结对于每一个的启动都是至关重要的。 心动周期。为了维持窦房结中恒定的舒张期自发去极化， 通过右冠状动脉输送到淋巴结。尽管许多组织已经调查了 尽管我们对负责节点起搏的机制仍然有非常有限的了解， 在静息或升高的生理条件期间调节窦房结中的血流（即， 锻炼）。淋巴结的充分灌注至关重要，因为临床证据表明， 窦房结动脉的阻塞是促血栓形成的。以前的研究表明， 窦房结的上级和下级区域之间微血管密度的差异， 但其重要性尚不清楚。此外，在心力衰竭期间，患者表现出以下缺陷： 窦房结功能正常和冠状动脉血管密度降低。这个项目的首要目标是 该项目的目的是确定在交感神经系统激活过程中如何调节血流，以及 这种调节在诸如心力衰竭的疾病期间受到影响。首先，我们计划调查空间 交感神经和参与介导血管阻力的细胞类型之间的关系（即， 血管平滑肌细胞、内皮细胞和周细胞），以确定 交感神经激活是介导的。接下来，我们将从窦房结分离微血管， 阐明交感神经激活的作用，以确定是否上级和下窦房结 动脉对神经激活的反应不同。最后，我们将研究小鼠心力衰竭 引起微血管密度和对交感神经刺激的反应的变化。该项目将 作为未来研究的基础，通过解剖血液流动调节的关键组成部分， 窦房结