ADENOSINE AND ENDOTHELIN IN MYOCARDIAL REPERFUSION

心肌再灌注中的腺苷和内皮素

基本信息

  • 批准号:
    2219767
  • 负责人:
  • 金额:
    $ 22.44万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1988
  • 资助国家:
    美国
  • 起止时间:
    1988-07-01 至 1995-08-31
  • 项目状态:
    已结题

项目摘要

Myocardial infarction remains a major cause of morbidity and mortality in the U.S. One important determinant of early and late mortality is the extent of left ventricular dysfunction. Although early reperfusion by either pharmacologic or mechanical means has been conclusively shown to reduce cardiac mortality, less striking beneficial effects on left ventricular function and infarct size reduction have been demonstrated. This finding, in conjunction with the observation that administration of the endogenous nucleoside Adenosine after reperfusion significantly enhances myocardial salvage in experimental models, supports the hypothesis that reperfusion per se may be detrimental to the previously ischemic but viable cardiac tissue ("REPERFUSION INJURY"). Reperfusion is associated with accelerated structural abnormalities in the vasculature resulting in progressive microcirculatory failure ("no- reflow" phenomenon). The etiology of this phenomenon remains unknown but may be produced by both hum oral and mechanical factors. ENDOTHELlN, a potent, long-acting vasoconstrictor peptide, has been shown to be significantly increased in the coronary sinus effluent in the experimental preparation of ischemia/reperfusion. Intravenous ADENOSINE, in a dose which enhances myocardial salvage, prevents this increase in the early reperfusion period. This proposal will attempt to define the role of ENDOTHELIN in the pathogenesis of reperfusion injury and the mechanisms whereby ADENOSINE modulates its release. Initial studies will determine the time course of the increase of ENDOTHELIN with various durations of ischemia. The role of ENDOTHELIN as an important mediator of reperfusion injury will be explored utilizing specific monoclonal ENDOTHELIN antibodies and a specific ENDOTHELIN receptor antagonist in the intact rabbit model. The mechanism whereby ADENOSINE attenuates the release and/or production of ENDOTHELIN will be determined utilizing both,in vivo and in vitro models. In situ hybridization techniques will be employed in both model systems to determine if ADENOSINE alters ENDOTHELIN gene production via activation of extracellular purinergic receptors. The role of activated neutrophils and platelets will be explored in an in vivo canine model of endothelial injury. The effect of ENDOTHELIN on neutrophil-endothelial interactions will be examined utilizing endothelial cell cultures. These studies will provide important information regarding the role of ENDOTHELIN in myocardial reperfusion injury and whether modulation of this peptide accounts for the beneficial effects of ADENOSINE on myocardial reperfusion injury further understanding of the mechanisms of action of ADENOSINE in protecting against reperfusion injury would allow for important advances in the treatment of evolving myocardial infarction.
心肌梗死仍然是发病率和死亡率的主要原因

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(1)
Mechanisms and therapy of myocardial reperfusion injury.
心肌再灌注损伤的机制和治疗。
  • DOI:
  • 发表时间:
    1990
  • 期刊:
  • 影响因子:
    37.8
  • 作者:
    Forman,MB;Virmani,R;Puett,DW
  • 通讯作者:
    Puett,DW
Role of endothelin in a rabbit model of acute myocardial infarction: effects of receptor antagonists.
内皮素在兔急性心肌梗死模型中的作用:受体拮抗剂的作用。
  • DOI:
    10.1097/00005344-199612000-00007
  • 发表时间:
    1996
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Vitola,JV;Forman,MB;Holsinger,JP;Kawana,M;Atkinson,JB;Quertermous,T;Jackson,EK;Murray,JJ
  • 通讯作者:
    Murray,JJ
Reduction of myocardial infarct size in rabbits and inhibition of activation of rabbit and human neutrophils by lidocaine.
利多卡因减少兔心肌梗塞面积并抑制兔和人中性粒细胞的活化。
  • DOI:
    10.1016/s0002-8703(97)70226-6
  • 发表时间:
    1997
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    Vitola,JV;Forman,MB;Holsinger,JP;Atkinson,JB;Murray,JJ
  • 通讯作者:
    Murray,JJ
{{ 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 }}

John J. Murray其他文献

988-7 Endothelin ET<sub>A/B</sub> Receptor Antagonist Reduces Infarct Size: A Novel Therapy for Acute Myocardial Infarction
  • DOI:
    10.1016/0735-1097(95)92747-s
  • 发表时间:
    1995-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    Joao V. Vitolaf;John Holsinger;Menryn B. Forman;Edwin K. Jackson;Masatoshi Kawana;Thomas Quertermous;John J. Murray
  • 通讯作者:
    John J. Murray
923-1 Inhibition of Neutrophil Function by Lidocaine as a Mechanism for the Beneficial Effect to Reduce Myocardial Reperfusion Injury
  • DOI:
    10.1016/0735-1097(95)91878-2
  • 发表时间:
    1995-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    João V. Vitola;John P. Holsinger;James Atkinson;Mervyn B. Forman;John J. Murray
  • 通讯作者:
    John J. Murray
923-3 Fluosol Reduces Myocardial Reperfusion Injury by Prolonged Suppression of Neutrophils by its Detergent Component (RheothRx) and not by Enhancing O<sub>2</sub>Delivery
  • DOI:
    10.1016/0735-1097(95)91880-7
  • 发表时间:
    1995-02-01
  • 期刊:
  • 影响因子:
  • 作者:
    João V. Vitola;David A. Ingram;John P. Holsinger;James B. Atkinson;Mervyn B. Forman;John J. Murray
  • 通讯作者:
    John J. Murray
Efficacy and Safety of a Novel, Single-dose Azithromycin Microsphere Formulation Versus 10 Days of Levofloxacin for the Treatment of Acute Bacterial Sinusitis in Adults
  • DOI:
    10.1016/j.otohns.2005.04.020
  • 发表时间:
    2005-08-01
  • 期刊:
  • 影响因子:
  • 作者:
    John J. Murray;Paz Emparanza;Eugenijus Lesinskas;Margaret Tawadrous;Jeanne D. Breen
  • 通讯作者:
    Jeanne D. Breen
Hypercalcemia in disseminated histoplasmosis. Aggravation by vitamin D.
播散性组织胞浆菌病中的高钙血症。
  • DOI:
    10.1016/0002-9343(85)90300-6
  • 发表时间:
    1985
  • 期刊:
  • 影响因子:
    0
  • 作者:
    John J. Murray;Craig R. Heim
  • 通讯作者:
    Craig R. Heim

John J. Murray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('John J. Murray', 18)}}的其他基金

Center for Cardiovascular Health Disparities Research at Meharry Medical College
梅哈里医学院心血管健康差异研究中心
  • 批准号:
    8289433
  • 财政年份:
    2011
  • 资助金额:
    $ 22.44万
  • 项目类别:
Center for Cardiovascular Health Disparities Research at Meharry Medical College
梅哈里医学院心血管健康差异研究中心
  • 批准号:
    8083231
  • 财政年份:
    2011
  • 资助金额:
    $ 22.44万
  • 项目类别:
PARTICIPANT AND CLINICAL INTERACTIONS RESOURCE (PCIR)
参与者和临床互动资源 (PCIR)
  • 批准号:
    8359880
  • 财政年份:
    2011
  • 资助金额:
    $ 22.44万
  • 项目类别:
MULTIDISCIPLINARY TRAINING AND CAREER DEVELOPMENT ACTIVITIES
多学科培训和职业发展活动
  • 批准号:
    8359876
  • 财政年份:
    2011
  • 资助金额:
    $ 22.44万
  • 项目类别:
MMC and VICC: Partnership for Survivorship (1 of 2)
MMC 和 VICC:幸存者合作伙伴关系(2 中的 1)
  • 批准号:
    8540359
  • 财政年份:
    2010
  • 资助金额:
    $ 22.44万
  • 项目类别:
MMC and VICC: Partnership for Survivorship (1 of 2)
MMC 和 VICC:幸存者合作伙伴关系(2 中的 1)
  • 批准号:
    8326219
  • 财政年份:
    2010
  • 资助金额:
    $ 22.44万
  • 项目类别:
MULTIDISCIPLINARY TRAINING AND CAREER DEVELOPMENT ACTIVITIES
多学科培训和职业发展活动
  • 批准号:
    8173600
  • 财政年份:
    2010
  • 资助金额:
    $ 22.44万
  • 项目类别:
PARTICIPANT AND CLINICAL INTERACTIONS RESOURCE (PCIR)
参与者和临床互动资源 (PCIR)
  • 批准号:
    8173604
  • 财政年份:
    2010
  • 资助金额:
    $ 22.44万
  • 项目类别:
Meharry Medical College Minority-Based Community Clinical Oncology Program
梅哈里医学院少数民族社区临床肿瘤学项目
  • 批准号:
    8511579
  • 财政年份:
    2004
  • 资助金额:
    $ 22.44万
  • 项目类别:
Meharry Medical College Minority-Based Community Clinical Oncology Program
梅哈里医学院少数民族社区临床肿瘤学项目
  • 批准号:
    8308753
  • 财政年份:
    2004
  • 资助金额:
    $ 22.44万
  • 项目类别:

相似海外基金

Supporting Canadian Veterans with Service Dogs
用服务犬支持加拿大退伍军人
  • 批准号:
    477734
  • 财政年份:
    2024
  • 资助金额:
    $ 22.44万
  • 项目类别:
    Salary Programs
Research on a guide dog and its user's transportation behavior and barrier for promotion of guide dogs
导盲犬及其使用者的运输行为及导盲犬推广障碍研究
  • 批准号:
    23K04080
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Is phosphorylation of BRCA2 in M phase associated with tumorigenesis in dogs?
M期BRCA2磷酸化与狗的肿瘤发生有关吗?
  • 批准号:
    23K05575
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Clinical, molecular, and immune characterization of naturally occurring osteosarcoma in dogs
犬自然发生的骨肉瘤的临床、分子和免疫特征
  • 批准号:
    10717426
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
CAREER: Integrating brain-behavior evolution with real-world science impacts through neuroscience of working dogs
职业:通过工作犬的神经科学将大脑行为进化与现实世界的科学影响相结合
  • 批准号:
    2238071
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
    Continuing Grant
Combining Radiation, Allogeneic Natural Killer Immunotherapy, and PD-L1 blockade in Dogs with Naturally-Occurring Melanoma
结合放疗、同种异体自然杀伤免疫疗法和 PD-L1 阻断治疗患有天然黑色素瘤的狗
  • 批准号:
    10679952
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
Is the gut important in multiple joint osteoarthritis? A multimodal investigation in humans and pet dogs
肠道在多关节骨关节炎中重要吗?
  • 批准号:
    10859955
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
A child's best friend: Behavioral, neural, and endocrinological mechanisms of longitudinal social bond formation and stress buffering effects in children and pet dogs
孩子最好的朋友:儿童和宠物狗纵向社会纽带形成和压力缓冲效应的行为、神经和内分泌机制
  • 批准号:
    10607449
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
Companion dogs: sentinels for multimorbidity of human neurocognitive-sensory aging and susceptibility to Alzheimer’s disease and related dementias
伴侣犬:人类神经认知感觉衰老和阿尔茨海默病及相关痴呆症易感性的哨兵
  • 批准号:
    10716497
  • 财政年份:
    2023
  • 资助金额:
    $ 22.44万
  • 项目类别:
Understanding and preventing fear and aggression in companion cats and dogs
了解并预防伴侣猫和狗的恐惧和攻击行为
  • 批准号:
    RGPIN-2019-06012
  • 财政年份:
    2022
  • 资助金额:
    $ 22.44万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了