Mechanisms Mediating Hypotension to Anthrax Lethal Toxin

炭疽致死毒素介导低血压的机制

基本信息

  • 批准号:
    7750596
  • 负责人:
  • 金额:
    $ 22.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-01-01 至 2012-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Bacillus anthracis infection is a deadly pathophysiological condition and a major bioterrorism health threat. The treatment of patients infected with inhalational Bacillus anthracis in the United States was complicated by progressive decreases in arterial blood pressure. To investigate the pathogenesis of the shock-like reduction in arterial blood pressure with Bacillus anthracis, investigators at the National Institutes of Health developed a rat model using continuous infusions of anthrax lethal toxin (LeTx) and anthrax edema toxin (ETx) (these toxins are central to the pathogenesis of Bacillus anthracis). These investigators reported that LeTx and ETx infusions produced hypotension; however, mechanisms mediating the depression in arterial blood pressure are not known. Although neurological complications are a fundamental component of Bacillus anthracis infections, no studies have determined the effect of Bacillus anthracis infection on sympathetic nerve outflow, the fundamental link between central sympathetic neural circuits and regulation of cardiac output, vascular resistance, and arterial blood pressure. The proposed studies will, for the first time, advance the hypothesis that Bacillus anthracis infection mediates progressive hypotension by altering regulation of sympathetic nerve outflow, cardiac output, vascular reactivity, and peripheral vascular conductance. An integrative and multifaceted experimental approach involving sympathetic nerve, cardiac output, left ventricular function, alpha-adrenergic vasoconstrictor, endothelium-dependent and -independent vasodilation, and regional vascular conductance measurements to continuous LeTx, ETx, and combined LeTx+ETx infusions will be completed in rats to address four questions. 1. Does infusion of Bacillus anthracis toxins produce sympathoinhibition? 2. Is cardiac function depressed in response to infusion of Bacillus anthracis toxins? 3. Do infusions of Bacillus anthracis toxins reduce 11-adrenergic receptor vascular responsiveness and alter endothelium-dependent and - independent vasodilation? 4. Is the distribution of visceral and peripheral blood flow altered by infusion of Bacillus anthracis toxins? The elaboration of mechanisms mediating hypotension to LeTx and ETx infusions is important for determining the efficacy of conventional therapy and the development of improved therapies in response to Bacillus anthracis infection. PUBLIC HEALTH RELEVANCE: Bacillus anthracis infection is a deadly pathophysiological state and a serious bioterrorism health threat. The proposed studies are designed to determine sympathetic nervous system and cardiovascular mechanisms responsible for the reduction in arterial blood pressure during infusion of anthrax lethal toxin. Further understanding of the mechanisms mediating sympathetic nerve and cardiovascular alterations to anthrax lethal toxin is critical for determining the efficacy of conventional therapy and the development of improved therapies for Bacillus anthracis infection.
描述(由申请人提供):炭疽杆菌感染是一种致命的病理生理状况,也是主要的生物恐怖主义健康威胁。在美国,吸入性炭疽杆菌感染患者的治疗因动脉血压逐渐下降而变得复杂。为了研究炭疽杆菌导致动脉血压出现休克样降低的发病机制,美国国立卫生研究院的研究人员通过持续输注炭疽致死毒素 (LeTx) 和炭疽水肿毒素 (ETx)(这些毒素是炭疽杆菌发病机制的核心)开发了一种大鼠模型。这些研究人员报告称,LeTx 和 ETx 输注会导致低血压;然而,调节动脉血压降低的机制尚不清楚。尽管神经系统并发症是炭疽杆菌感染的一个基本组成部分,但尚无研究确定炭疽杆菌感染对交感神经流出的影响,而交感神经流出是中枢交感神经回路与心输出量、血管阻力和动脉血压调节之间的基本联系。拟议的研究将首次提出这样的假设:炭疽杆菌感染通过改变交感神经流出、心输出量、血管反应性和外周血管电导的调节来介导进行性低血压。将在大鼠中完成一项综合、多方面的实验方法,涉及交感神经、心输出量、左心室功能、α-肾上腺素能血管收缩剂、内皮依赖性和非依赖性血管舒张,以及对连续 LeTx、ETx 和联合 LeTx+ETx 输注的局部血管电导测量,以解决四个问题。 1. 输注炭疽杆菌毒素是否会产生交感神经抑制作用? 2. 输注炭疽杆菌毒素是否会导致心脏功能下降? 3. 输注炭疽杆菌毒素是否会降低 11-肾上腺素受体血管反应性并改变内皮依赖性和非依赖性血管舒张? 4. 输注炭疽杆菌毒素是否会改变内脏和外周血流的分布? LeTx 和 ETx 输注介导低血压的机制的阐述对于确定常规疗法的功效和开发针对炭疽杆菌感染的改进疗法非常重要。公共卫生相关性:炭疽杆菌感染是一种致命的病理生理状态,也是严重的生物恐怖主义健康威胁。拟议的研究旨在确定在输注炭疽致命毒素期间导致动脉血压降低的交感神经系统和心血管机制。进一步了解介导炭疽致死毒素的交感神经和心血管改变的机制对于确定传统疗法的功效和开发针对炭疽杆菌感染的改进疗法至关重要。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Bacillus anthracis lethal toxin induces complex changes in sympathetic nerve discharge regulation.
  • DOI:
    10.1016/j.autneu.2012.06.007
  • 发表时间:
    2012-09-25
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Kenney, M. J.;Mosher, L. J.;Fels, R. J.
  • 通讯作者:
    Fels, R. J.
Is visceral sympathoexcitation to heat stress dependent on activation of ionotropic excitatory amino acid receptors in the rostral ventrolateral medulla?
{{ 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 }}

Michael J Kenney其他文献

Michael J Kenney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('Michael J Kenney', 18)}}的其他基金

Build-out of an Imaging and Behavioral Neuroscience Facility for Hispanic Health Disparities at UTEP
在 UTEP 为西班牙裔健康差异建立影像和行为神经科学设施
  • 批准号:
    10374638
  • 财政年份:
    2021
  • 资助金额:
    $ 22.2万
  • 项目类别:
Sympathetic Neural Regulation and Aging: Medullary Mechanisms and Strategies
交感神经调节与衰老:髓质机制和策略
  • 批准号:
    8851480
  • 财政年份:
    2012
  • 资助金额:
    $ 22.2万
  • 项目类别:
Sympathetic Neural Regulation and Aging: Medullary Mechanisms and Strategies
交感神经调节与衰老:髓质机制和策略
  • 批准号:
    8718970
  • 财政年份:
    2012
  • 资助金额:
    $ 22.2万
  • 项目类别:
Sympathetic Neural Regulation and Aging: Medullary Mechanisms and Strategies
交感神经调节与衰老:髓质机制和策略
  • 批准号:
    8439565
  • 财政年份:
    2012
  • 资助金额:
    $ 22.2万
  • 项目类别:
Sympathetic Neural Regulation and Aging: Medullary Mechanisms and Strategies
交感神经调节与衰老:髓质机制和策略
  • 批准号:
    8545662
  • 财政年份:
    2012
  • 资助金额:
    $ 22.2万
  • 项目类别:
Mechanisms Mediating Hypotension to Anthrax Lethal Toxin
炭疽致死毒素介导低血压的机制
  • 批准号:
    7588330
  • 财政年份:
    2009
  • 资助金额:
    $ 22.2万
  • 项目类别:
Aging and Heart Failure are not Similar Syndromes of Sympathetic Dysregulation
衰老和心力衰竭并不是类似的交感神经失调综合征
  • 批准号:
    7531335
  • 财政年份:
    2008
  • 资助金额:
    $ 22.2万
  • 项目类别:
Aging and Heart Failure are not Similar Syndromes of Sympathetic Dysregulation
衰老和心力衰竭并不是类似的交感神经失调综合征
  • 批准号:
    7665576
  • 财政年份:
    2008
  • 资助金额:
    $ 22.2万
  • 项目类别:
BRITE Veterinary Student Program
BRITE 兽医学生计划
  • 批准号:
    7932091
  • 财政年份:
    2003
  • 资助金额:
    $ 22.2万
  • 项目类别:
BRITE Veterinary Student Program
BRITE 兽医学生计划
  • 批准号:
    8322613
  • 财政年份:
    2003
  • 资助金额:
    $ 22.2万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 22.2万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了