Elucidating sympathetic vasoconstrictor mechanisms of autonomic dysreflexia in persons with spinal cord injury

阐明脊髓损伤患者自主神经反射异常的交感血管收缩机制

基本信息

项目摘要

Autonomic dysreflexia (AD) is a potentially life-threatening consequence of cervical and high thoracic (above T6) spinal cord injury (SCI) characterized by abruptly high elevations in blood pressure in response to noxious stimuli below the injury level. 1,2 In addition to the potential morbidity caused by acute rise in blood pressure, recurrent AD over a longer period has been associated with changes in vascular structure that lead to CVD 3,4and impaired immune function, 5 which are both leading causes of mortality in persons with SCI. 6 While peripheral arteriolar vasoconstriction (VC) is documented to be pronounced during AD,7,8 The pathophysiological mechanisms of this VC are not well defined. A few proposed mechanisms include: 1) increase in neuronal release of norepinephrine (NE) and co-transmitters (CT); 2) post-junctional alpha-receptor hypersensitivity; 3) impaired reuptake of NE and/or 4) increases in circulating catecholamines (Epinephrine > NE) from adrenal stimulation.2,9 None of these mechanisms has been fully proven or is widely accepted. Furthermore, there are no known effective preventative or targeted treatment of the underlying pathophysiology of the AD, as the mechanisms are unknown. Current clinical care of AD with pharmacologic therapies is not without potential for significant side effects. Pharmacologic treatment includes short acting anti- hypertensives (e.g.; nitroglycerin and nifedipine), which can cause systemic hypotension. There is no known treatment targeting the underlying arteriolar vasoconstriction mechanisms of AD since they are unknown. Elucidating the underlying pathophysiology will facilitate the development of targeted treatment(s) to attenuate AD without significant adverse side effects. Our proposal aims to take the next step in elucidating the underlying pathophysiology of VC during AD. We aim to test one of the proposed mechanisms using a novel non-invasive technique never before used in studies testing VC pathology during AD. Specifically we will test following hypotheses: 1) Blockade of pre-synaptic neural release of NE and CT will abolish cutaneous VC during AD and 2) blockade of post synaptic alpha adrenergic receptors will decrease but not fully abolish VC during AD. Arterioles of the skin are easily accessible to test these hypotheses. We will use a novel and non- invasive technique of local iontophoretic delivery of pharmacologic agents combined with skin blood flow monitoring by laser Doppler flowmetry (LDF) and mean blood pressure (MAP) monitoring to define the underlying pathophysiology.10 Specific AIM 1 will compare the impact of a sympathetic neuronal blocking agent (bretylium = BT; blocks release of NE and co-transmitters from sympathetic noradrenergic nerves)) on cutaneous vascular conductance (CVC=LDF/MAP) during an AD episode at BT treated and control (CON) sites on a forearm and posterior calf. CVC will be compared at baseline = BL at normotension then every 20 seconds during AD stimulated by bladder percussion. If the increased arteriolar vasoconstriction is due to increased neuronal release of NE and CT then the sites treated with BT will demonstrate comparatively less vasoconstriction. Specific AIM 2 will evaluate the impact of non-selective alpha-adrenergic receptor blockade (phentolamine – PT) on CVC during AD. Before using PT during AD, the optimal PT dose to block alpha receptors will be determined by utilizing alpha 1 and 2 agonists with PT. After the PT dose required for total alpha –adrenergic blockade is determined, similar to AIM 1, CVC will be measured at PT treated and adjacent untreated CON sites. If the increased arteriolar vasoconstriction is due to NE release, then the CVC changes of PT and CON sites will differ. Ultimately, elucidating this information will 1) guide treatment, and potentially prophylaxis, to better target the underlying pathophysiology of VC during AD, with less systemic side effects and 2) help prevent the vascular adaptations with potential to contribute to CVD and impaired immunity associated with recurrent AD that both may increase mortality.
自主神经反射障碍(AD)是颈椎病和高胸椎病的潜在威胁

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 }}

DEAN L KELLOGG其他文献

UNMASKING THE MIMIC: CRYPTOCOCCUS GATTII MASQUERADING AS LUNG CANCER IN AN IMMUNOCOMPETENT PATIENT
  • DOI:
    10.1016/j.chest.2023.07.739
  • 发表时间:
    2023-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    JOHN SUDER;DEAN L KELLOGG;KEVIN PROUD
  • 通讯作者:
    KEVIN PROUD
NOVEL USE OF MONTHLY PULSE METHYLPREDNISOLONE INFUSIONS IN PATIENTS WITH NON-IPF ILD: A SINGLE-CENTER RETROSPECTIVE ANALYSIS
  • DOI:
    10.1016/j.chest.2023.07.2062
  • 发表时间:
    2023-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    FATIMA DOLLAR;DEAN L KELLOGG;ANOOP M NAMBIAR;JAY I PETERS;JESSE SHERRATT
  • 通讯作者:
    JESSE SHERRATT
EMERGENT TREATMENT FOR ACUTE HYPOXIC RESPIRATORY FAILURE: ASSESSMENT OF THREE DEVICES
  • DOI:
    10.1016/j.chest.2023.07.3965
  • 发表时间:
    2023-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    YASMINE KHAIRANDISH;DEAN L KELLOGG;FERNANDO A HERNANDEZ;THOMAS J STOKES;MEGAN L LLAMAS;JAY I PETERS
  • 通讯作者:
    JAY I PETERS
PREDICTORS OF NONRESPONSE TO IMMUNOSUPPRESSANTS IN NON-IPF ILD: A SINGLE-CENTER RETROSPECTIVE STUDY
  • DOI:
    10.1016/j.chest.2024.06.2000
  • 发表时间:
    2024-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    SERGIO VALLEJO;SEBASTIAN OCROSPOMA HERAUD;DEAN L KELLOGG;FATIMA DOLLAR;JAY I PETERS;ANOOP M NAMBIAR
  • 通讯作者:
    ANOOP M NAMBIAR
DECODING PULMONARY ADENOCARCINOMA'S DECEPTION
  • DOI:
    10.1016/j.chest.2024.06.2671
  • 发表时间:
    2024-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    MIN JI SON;SERGIO VALLEJO;NICHOLAS J SCHLUND;JOZEF OWEIS;DEAN L KELLOGG
  • 通讯作者:
    DEAN L KELLOGG

DEAN L KELLOGG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('DEAN L KELLOGG', 18)}}的其他基金

Elucidating sympathetic vasoconstrictor mechanisms of autonomic dysreflexia in persons with spinal cord injury
阐明脊髓损伤患者自主神经反射异常的交感血管收缩机制
  • 批准号:
    10404588
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
An innovative proof-of-concept approach to identify age-modulating drugs capable of reversing inflammation and re-setting the epigenetic clock
一种创新的概念验证方法,用于识别能够逆转炎症和重置表观遗传时钟的年龄调节药物
  • 批准号:
    10264863
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
An innovative proof-of-concept approach to identify age-modulating drugs capable of reversing inflammation and re-setting the epigenetic clock
一种创新的概念验证方法,用于识别能够逆转炎症和重置表观遗传时钟的年龄调节药物
  • 批准号:
    10040501
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
TRPV1 mediation of local vasoconstrictor reflexes in spinal cord injured humans
TRPV1 介导脊髓损伤人体局部血管收缩反射
  • 批准号:
    8570431
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
TRPV1 mediation of local vasoconstrictor reflexes in spinal cord injured humans
TRPV1 介导脊髓损伤人体局部血管收缩反射
  • 批准号:
    8655188
  • 财政年份:
    2013
  • 资助金额:
    --
  • 项目类别:
Translational Model Development: Rapamycin, Aging, and Endothelial Dysfunction
转化模型开发:雷帕霉素、衰老和内皮功能障碍
  • 批准号:
    8515283
  • 财政年份:
    2012
  • 资助金额:
    --
  • 项目类别:
MECHANISMS OF CUTANEOUS ACTIVE VASODILATION IN HUMANS
人类皮肤主动血管舒张的机制
  • 批准号:
    7718731
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
MECHANISMS OF CUTANEOUS ACTIVE VASODILATION IN HUMANS
人类皮肤主动血管舒张的机制
  • 批准号:
    7627529
  • 财政年份:
    2007
  • 资助金额:
    --
  • 项目类别:
MECHANISMS OF CUTANEOUS ACTIVE VASODILATION IN HUMANS
人类皮肤主动血管舒张的机制
  • 批准号:
    7378192
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
MECHANISMS OF CUTANEOUS ACTIVE VASODILATION IN HUMANS
人类皮肤主动血管舒张的机制
  • 批准号:
    7204797
  • 财政年份:
    2005
  • 资助金额:
    --
  • 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:
    --
  • 项目类别:
    Fellowship
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:
    --
  • 项目类别:
    Continuing Grant
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:
    --
  • 项目类别:
    Research 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 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:
    --
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了