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.

Sinotrial节点是心脏中有组织和有节奏的电去极化的起源。后 离开窦节点，去极化散布在整个中庭，并通过房室的心室散布 节点和专门的传导途径，以引发激发反应耦合 心肌细胞。这种高度有条理的事件模式对于在整个过程中泵送血液至关重要 肺和全身循环。因此，窦节点对于每个人的启动至关重要 心脏周期。为了维持辛里氏节点中恒定的舒张自发去极化，血液是 通过右冠状动脉传递到节点。尽管许多团体都调查了 负责节点起搏的机制，我们继续对 在静息或升高的生理条件下，在辛里亚淋巴结中调节血流（即 锻炼）。由于临床证据表明损坏或 窦性淋巴结动脉的阻塞是促性心律失常的。以前的研究表明有 Sinotrial节点的上部和下区域之间的微血管密度的差异， 但是，这一点尚不清楚。此外，在心力衰竭期间，患者表现出缺陷 正常的窦淋巴结功能和冠状动脉血管密度的降低。总体目标 项目将确定在交感神经系统激活期间如何调节血液流量以及如何调节 该调节在心力衰竭等疾病期间受到影响。首先，我们计划调查空间 交感神经与介导血管抗性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）确定 介导交感神经激活。接下来，我们将从窦节点和 阐明交感神经激活的效果，以确定上弦和下鼻网节点是否 动脉对神经激活有所不同。最后，我们将研究鼠标心力衰竭 导致微血管密度的变化和对交感神经刺激的反应。这个项目将 通过剖析血流调节的关键组成部分作为未来研究的基础 Sinotrial节点。