ELECTROPHYSIOLOGICAL EFFECTS OF NEURAL REMODELING OF THE VENTRICLES

心室神经重塑的电生理效应

• 批准号: 8603270
• 负责人: KALYANAM SHIVKUMAR
• 金额: $ 37.98万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603270
• 关键词: Ablation; Adrenergic Agents; Adrenergic Fibers; Animal Model; Animals; Area; Arrhythmia; Attenuated; Autonomic nervous system; Bilateral; Biochemical; Biopsy; Cardiac; Cardiomyopathies; Cardiovascular system; Catheters; Cessation of life; Chest; Cicatrix; Clinical; Coronary; Disease; Efferent Neurons; Electrophysiology (science); Endocardium; Epicardium; Epidural Anesthesia; Excision; Fiber; Functional disorder; Ganglia; Goals; Health; Heart; Heart Transplantation; Histology; Human; Implantable Defibrillators; Infusion procedures; Knowledge; Left; Maps; Measurement; Morbidity - disease rate; Myocardial; Nerve; Nitroprusside; Norepinephrine; Operative Surgical Procedures; Output; Pathway interactions; Patients; Play; Prevention; Procedures; Property; Protocols documentation; Pulmonary artery structure; Recovery; Regulation; Research; Risk; Role; Structure of stellate ganglion; Sympathectomy; Sympathetic Ganglia; Testing; Therapeutic; Therapeutic Intervention; Thoracic spinal cord structure; United States; Ventricular; Ventricular Arrhythmia; Ventricular Fibrillation; Ventricular Remodeling; Ventricular Tachycardia; Ventricular septum; Work; adrenergic; base; clinical practice; cost; cost effective; density; improved; in vivo; mortality; nerve supply; novel; pericardial sac; prevent; public health relevance; regional difference; relating to nervous system; response; sudden cardiac death; therapy development

DESCRIPTION (provided by applicant): Sudden cardiac death (SCD) due to ventricular arrhythmias is the leading cause of mortality in the United States, resulting in 250,000 deaths/year. The autonomic nervous system plays a major role in the pathophysiology of arrhythmias leading to SCD and neuraxial modulation provides an important venue for therapeutic intervention. The major goal of our research is to investigate the role of cardiac sympathetic innervations in the genesis of arrhythmias, and that of neuraxial modulation in prevention of these arrhythmias in humans. The mechanisms underlying sympathetic control of myocardial excitability in normal and diseased human hearts, and specifically, regional differences (apex versus base, epicardium versus endocardium, right versus left stellate ganglion innervation) remain unknown and need to be studied. Further, myocardial scars seen in ischemic and non-ischemic cardiomyopathy show nerve sprouting at the border zone of scars due to neural remodeling, which has been implicated in the pathophysiology of ventricular arrhythmias. The functional effects of nerve stimulation in this setting and how neuraxial blockade works in humans in these diseases are still unknown and this knowledge can help guide therapy. In this proposal, electrophysiological effects of direct regional cardiac nerve stimulation and neuraxial modulation of the thoracic sympathetic ganglia will be investigated. Areas of the heart regulated by the right and left stellate ganglia will be delineated in patients undergoing interventional electrophysiology procedures and cardiac transplantation. Understanding neuraxial modulation has the potential to further develop therapies that target these pathways in the very near term. Therapies such as right, left, or bilateral cerviocothoracic sympathectomy which has been 're-introduced' into clinical practice (by our group and others) already show a lot of promise and could emerge as novel/elegant therapies that are also cost-effective for the prevention of SCD. Therefore, neuraxial modulation is an approach that has the potential to have a global impact given the prohibitive high cost and morbidity associated with implantable defibrillators which prevent their expanded use.

描述（由申请人提供）：由于心室心律不齐而导致的心脏突然死亡（SCD）是美国死亡率的主要原因，每年死亡25万。自主神经系统在导致SCD和神经调节的心律不齐的病理生理学中起主要作用，为治疗干预提供了重要的场所。我们研究的主要目的是研究心律不齐的发生在心律不齐的起源中的作用，以及神经调节在预防人类心律失常中的作用。对正常和患病的人类心脏中心肌兴奋性的交感神经控制的机制，特别是区域差异（Apex vers base，心外膜与心内膜心脏，右对左星神经神经支配）仍然尚不清楚，需要研究并需要研究。此外，在缺血性和非缺血性心肌病中看到的心肌疤痕在神经重塑引起的疤痕边界区域发芽，这与心室心律不齐的病理生理有关。在这种情况下，神经刺激的功能效应以及这些疾病中人类中神经封锁的作用仍然未知，这些知识可以帮助指导治疗。在这一建议中，将研究直接区域心脏神经刺激和胸部交感神经的神经调节的电生理作用。在接受介入的电生理程序和心脏移植的患者中，将描绘受左右星状神经节调节的心脏区域。理解神经调节有可能在短期内进一步开发针对这些途径的疗法。右，左或双侧宫颈胸膜切除术等疗法已被“重新引入”临床实践（由我们的小组和其他人）已经显示出很大的希望，并且可以作为新颖/优雅的疗法出现，这些疗法也具有成本效益，这也具有成本效益。因此，鉴于与可植入的除颤器相关的高成本和发病率，神经调节是一种有可能产生全球影响的方法，从而阻止其扩大使用。