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
基本信息
- 批准号:10627577
- 负责人:
- 金额:$ 49.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-10 至 2028-07-31
- 项目状态:未结题
- 来源:
- 关键词:Action PotentialsAdrenergic AntagonistsAnimal ModelAnimalsAnti-Arrhythmia AgentsAntiinflammatory EffectAreaArrhythmiaAttenuatedAutonomic nervous systemCardiacCardiac MyocytesCardiomyopathiesCardiovascular DiseasesCessation of lifeChronicCicatrixComputer AssistedComputer ModelsComputer Vision SystemsData SetDiseaseDisease ProgressionDonor personElectrophysiology (science)EnsureExhibitsFamily suidaeFunctional disorderGoalsHealthHeartHeart DiseasesHeart TransplantationHeart failureHeterogeneityHumanHypertensionImplantIn VitroIndividualInfarctionInflammationInterventionIschemiaKineticsLeadLeft Ventricular Ejection FractionLinkLocationMapsMeasurementMeasuresMechanicsMediatingMorbidity - disease rateMuscle CellsMyocardialMyocardial InfarctionMyocardial IschemiaMyocardiumNerveNervous SystemNeuronsNeuropeptidesNeurotransmittersPathologicPatientsPatternPeptidesPerfusionPeriodicityPhysiologicalPlayPreparationPrevention therapyProcessReflex actionRiskRoleScanningSignal TransductionStimulusStructureStructure of stellate ganglionSudden DeathSympathectomyTechniquesTestingTherapeuticTherapeutic InterventionTimeTissuesTransplantationUnited StatesVentricularVentricular ArrhythmiaVentricular Tachycardiadata integrationdensitydisorder preventionin vivoindividual responseischemic cardiomyopathymortalitynerve supplyneuralneuromechanismneuroregulationneurotransmitter releasephysiologic stressorprotective effectresponsespatiotemporalstoichiometrysudden cardiac deathtargeted treatmenttherapeutic target
项目摘要
ABSTRACT – Project 1
Sudden cardiac death due to ventricular arrhythmias and heart failure are the leading causes morbidity and
mortality in the United States. The autonomic nervous system plays a major role in the pathophysiology of
arrhythmias and heart failure. Neuraxial modulation represents an important avenue for therapeutic
intervention. However, the structural and functional determinants of the release of neurotransmitters and
peptides in the myocardium in health and disease, which effectively govern cardiac excitability and mechanical
function, as well as propensity toward arrhythmias, remain largely unknown. Myocardial scars seen in ischemic
and nonischemic cardiomyopathy show abnormal innervation and nerve sprouting at the border zone of scars
due to neural remodeling, which have been implicated in the pathophysiology of ventricular arrhythmias. We
propose to test “The Spatiotemporal Heterogeneity of Neurotransmitter Release Hypothesis’ – which
postulates that scars alter the ultrastructure of nerves and cause non-uniform reflex-mediated neurotransmitter
release in the myocardium and represents a crucial/proximate cause of lethal arrhythmias. The major goal of
this project is to investigate the structural (myocardial) and functional (neural) changes in the heart that occur
because of heart disease and subsequently lead to ventricular arrhythmias. In aims 1 and 2, we will determine
the ultrastructure and define the nerve-myocyte stoichiometry and release profiles of neurotransmitters and
peptides in normal and diseased hearts in response to physiological stressors and specifically define areas of
non-uniform release of neurotransmitters. In aim 3, we will determine the underlying mechanism and potential
benefit of vagal nerve stimulation in mitigating the pathological remodeling related to scar formation and
autonomic innervation. Regional structural and functional changes in innervation of scar and border zone
regions will be studied using high density electrophysiological mapping and real time neurotransmitter and
neuropeptide measurements which will be correlated with structural changes at the border zones of infarcts
using tissue clearing techniques in a relevant large animal model and in human hearts. Understanding the
underlying myocardial and neural mechanisms leading to arrhythmias has the potential to develop and
precisely target therapies that inspire therapies for the prevention of sudden cardiac death and progression of
heart failure.
摘要-项目1
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
KALYANAM SHIVKUMAR其他文献
KALYANAM SHIVKUMAR的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
$ 49.29万 - 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:
$ 49.29万 - 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:
$ 49.29万 - 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:
$ 49.29万 - 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:
$ 49.29万 - 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:
$ 49.29万 - 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:
8458497 - 财政年份:2006
- 资助金额:
$ 49.29万 - 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:
8603270 - 财政年份:2006
- 资助金额:
$ 49.29万 - 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:
$ 49.29万 - 项目类别:
相似海外基金
SELECTIVE ADRENERGIC ANTAGONISTS & INTRAOCULAR PRESSURE
选择性肾上腺素能拮抗剂
- 批准号:
3038642 - 财政年份:1985
- 资助金额:
$ 49.29万 - 项目类别:














{{item.name}}会员




