The Role of Epinephrine in Neurally Mediated Syncope

肾上腺素在神经介导性晕厥中的作用

基本信息

批准号：
7679628
负责人：
SATISH R RAJ
金额：
$ 12.4万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7679628
关键词：
Accident and Emergency department Accounting Adrenal Glands Adrenergic beta-Agonists Adrenergic beta-Antagonists Affinity Agonist American Bradycardia Brain Clinical Epinephrine Frequencies Functional disorder Genetic Heterogeneity Genetic Polymorphism Goals Heart Diseases Hypovolemia Individual Individual Differences Isoproterenol Life Lower Body Negative Pressure Mediating Modeling Norepinephrine Pathogenesis Patients Peripheral Pharmaceutical Preparations Play Predisposition Principal Investigator Quality of life Reaction Receptors, Adrenergic, beta-1 Recurrence Reporting Role Stress Syncope Teaching Hospitals Testing Time Vasodilation Visit Withdrawal Work adrenergic block adrenergic receptor alpha-2b base beta-2 Adrenergic Receptors beta-adrenergic receptor experience hemodynamics improved prevent programs receptor response

项目摘要

Syncope is a common problem experienced by up to 30% of people fainting and accounting for 3% of emergency room visits. Recurrent syncope is seen in 30-50% of patients and is associated with a poor quality of life that improves when the frequency of syncope is reduced. The majority of these patients suffer from neurally mediated syncope (NMS). The traditional model of NMS pathophysiology has focused on prior heightened sympathetic activation, followed by a sudden withdrawal of sympathetic tone and increase in vagal tone, with resultant vasodilation and bradycardia. Recent studies have found that the level of epinephrine rises PRIOR to syncope. In Specific Aim #1, we will determine the contributions of epinephrine release and clearance to the elevated epinephrine levels. A beta adreneroreceptor agonist similar to epinephrine, isoproterenol is commonly used clincially to induce neurally mediated syncope. Beta- blocking drugs, in particular those with beta-2 antagonism (the receptor at which endogenous epinephrine promotes vasodilation), prevent tilt-induced syncope, and might prevent clinical syncope. In Specific Aim #2, we will experimentally increase the epinephrine level and test whether this induces neurally mediated syncope. The response to epinephrine is likely to be substantially influenced by genetic heterogeneity in adrenoreceptors. Polymorphisms of these receptors might well account for inter-individual differences in sensitivity to the hemodynamic effects of epinephrine, and possibly in consequence, also susceptibility to syncope. In Specific Aim #3, we will assess the susceptibility to syncope based upon common polymorphisms of the alpha-2B adrenoreceptor and the beta-2 adrenoreceptor. Using these Specific Aims, we will test the hypothesis that epinephrine or its receptors play an important role in the pathogenesis of neurally mediated syncope

晕厥是多达30％的晕厥和占3％的人的常见问题急诊室访问。在30-50％的患者中可以看到复发性晕厥，并且与较差有关当晕厥频率降低时，生活质量会改善。这些患者大多数遭受来自神经介导的晕厥（NMS）。 NMS病理生理学的传统模型集中于先验同情激活增加，然后突然撤回交感神经并增加迷走态，导致血管舒张和心动过缓。最近的研究发现肾上腺素在晕厥之前上升。在特定的目标＃1中，我们将确定肾上腺素的贡献肾上腺素水平升高的释放和间隙。类似于肾上腺素，异丙肾上腺素通常用于cRINCINE诱导神经介导的晕厥。 β-阻塞药物，特别是患有β-2拮抗作用的药物（内源性肾上腺素促进的受体血管舒张），防止倾斜诱导的晕厥，并可能防止临床晕厥。在特定的目标＃2中，我们将实验上增加肾上腺素水平，并测试这是否诱导神经介导的晕厥。这对肾上腺素的反应可能会受到肾上腺受体遗传异质性的显着影响。这些受体的多态性很可能说明了对个人的敏感性差异肾上腺素的血液动力学作用，也可能因此，也对晕厥的敏感性。在具体目的＃3，我们将根据基于常见的多态性评估晕厥的敏感性 alpha-2b肾上腺受体和β-2肾上腺受体。使用这些特定目标，我们将测试假设肾上腺素或其受体在神经介导的发病机理中起重要作用昏厥

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Are small observational studies sufficient evidence for a recommendation of head-up sleeping in all patients with debilitating orthostatic hypotension? MacLean and Allen revisited after 70 years.

小型观察性研究是否有足够的证据来建议所有患有衰弱性直立性低血压的患者进行平视睡眠？

DOI：
10.1007/s10286-009-0522-3
发表时间：
2009
期刊：
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
影响因子：
0
作者：
Wieling,Wouter;Raj,SR;Thijs,RD
通讯作者：
Thijs,RD

Highlights in clinical autonomic neurosciences: orthostatic tachycardia and orthostatic hypotension.

临床自主神经科学的亮点：直立性心动过速和直立性低血压。