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

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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.