ELECTROPHYSIOLOGICAL EFFECTS OF NEURAL REMODELING OF THE VENTRICLES

心室神经重塑的电生理效应

基本信息

项目摘要

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):室性心律失常引起的心源性猝死 (SCD) 是美国的首要死因,每年导致 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发挥着重要作用,轴神经调节为治疗干预提供了重要场所。我们研究的主要目标是研究心脏交感神经支配在心律失常发生中的作用,以及轴神经调节在预防人类心律失常中的作用。正常和患病人类心脏中交感神经控制心肌兴奋性的机制,特别是区域差异(心尖与基部、心外膜与心内膜、右星状神经节与左星状神经节神经支配)仍然未知,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显示由于神经重塑而在疤痕边缘区域出现神经萌芽,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影响以及椎管阻滞在这些疾病中如何在人类中发挥作用仍然未知,这些知识可以帮助指导治疗。在该提案中,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。将在接受介入电生理学手术和心脏移植的患者中描绘出由左右星状神经节调节的心脏区域。了解椎管内调节有可能在短期内进一步开发针对这些通路的疗法。右、左或双侧颈胸交感神经切除术等疗法已(由我们小组和其他人)“重新引入”临床实践,已经显示出很大的希望,并且可能成为新颖/优雅的疗法,并且对于患者来说也具有成本效益。预防SCD。因此,考虑到与植入式除颤器相关的高昂成本和发病率阻碍了其广泛使用,椎管内调制是一种有可能产生全球影响的方法。

项目成果

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KALYANAM SHIVKUMAR其他文献

KALYANAM SHIVKUMAR的其他文献

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{{ truncateString('KALYANAM SHIVKUMAR', 18)}}的其他基金

Cardiac Neuromodulation: Mechanisms and Therapeutics
心脏神经调节:机制和治疗
  • 批准号:
    10627573
  • 财政年份:
    2023
  • 资助金额:
    $ 37.98万
  • 项目类别:
Neural Control of Myocardial Excitability at the Nerve Myocyte Interface
神经肌细胞界面心肌兴奋性的神经控制
  • 批准号:
    10627577
  • 财政年份:
    2023
  • 资助金额:
    $ 37.98万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10627574
  • 财政年份:
    2023
  • 资助金额:
    $ 37.98万
  • 项目类别:
CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES
人类心脏神经调节:机制
  • 批准号:
    10190645
  • 财政年份:
    2019
  • 资助金额:
    $ 37.98万
  • 项目类别:
CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES
人类心脏神经调节:机制
  • 批准号:
    9808011
  • 财政年份:
    2019
  • 资助金额:
    $ 37.98万
  • 项目类别:
CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES
人类心脏神经调节:机制
  • 批准号:
    10428718
  • 财政年份:
    2019
  • 资助金额:
    $ 37.98万
  • 项目类别:
Electrophysiological Effects of Neural Remodeling of the Ventricles
心室神经重塑的电生理效应
  • 批准号:
    7228832
  • 财政年份:
    2006
  • 资助金额:
    $ 37.98万
  • 项目类别:
Electrophysiological Effects of Neural Remodeling of the Ventricles
心室神经重塑的电生理效应
  • 批准号:
    7417817
  • 财政年份:
    2006
  • 资助金额:
    $ 37.98万
  • 项目类别:
Electrophysiological Effects of Neural Remodeling of the Ventricles
心室神经重塑的电生理效应
  • 批准号:
    7616206
  • 财政年份:
    2006
  • 资助金额:
    $ 37.98万
  • 项目类别:
Electrophysiological Effects of Neural Remodeling of the Ventricles
心室神经重塑的电生理效应
  • 批准号:
    7078849
  • 财政年份:
    2006
  • 资助金额:
    $ 37.98万
  • 项目类别:

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The Role and Branching Dynamics of Sympathetic Nerves in Ovarian Folliculogenesis
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  • 批准号:
    10607058
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    2023
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