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(申请人提供)：由室性心律失常引起的心脏性猝死(SCD)是美国主要的死亡原因，每年造成250,000人死亡。自主神经系统在导致SCD的心律失常的病理生理学中起着重要作用，神经轴调节为治疗干预提供了重要场所。我们研究的主要目的是探讨心脏交感神经支配在心律失常发生中的作用，以及神经轴调节在人类预防这些心律失常中的作用。交感神经控制正常人和疾病心脏心肌兴奋性的机制，特别是区域差异(心尖与心底、心外膜与心内膜、右与左星状神经节支配)仍不清楚，需要进行研究。此外，在缺血性和非缺血性心肌病中所见的心肌瘢痕由于神经重构而在疤痕的边缘区域出现神经萌发，这与室性心律失常的病理生理学有关。在这种情况下，神经刺激的功能效应以及神经轴阻滞在人类中如何在这些疾病中发挥作用仍是未知的，这一知识可以帮助指导治疗。在这项建议中，将研究直接局部心脏神经刺激和胸交感神经节的神经轴调节的电生理效应。在接受介入性电生理程序和心脏移植的患者中，将描绘由左右星状神经节调节的心脏区域。了解神经轴调节有可能在短期内进一步开发针对这些通路的治疗方法。治疗方法，如右、左或双侧颈胸交感神经切断术，已经(由我们团队和其他人)重新引入临床实践，已经显示出很大的前景，并可能成为预防SCD的新的/优雅的疗法，也是具有成本效益的。因此，神经轴调制是一种有可能产生全球影响的方法，因为与植入式除颤器相关的高昂成本和发病率阻碍了它们的推广使用。