ADENOSINE AND ENDOTHELIN IN MYOCARDIAL REPERFUSION
ADENOSINE AND ENDOTHELIN IN MYOCARDIAL REPERFUSION
批准号:
2219767
负责人:
John J. Murray
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
项目状态:
已结题
起止时间:
1988-07-01 至 1995-08-31
中文摘要
心肌梗死仍然是发病率和死亡率的主要原因
英文摘要
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.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
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:
Circulation
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:
Journal of cardiovascular pharmacology
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:
American heart journal
影响因子:
4.8
作者:
[Vitola,JV, Forman,MB, Holsinger,JP, Atkinson,JB, Murray,JJ]
通讯作者:
Murray,JJ
Center for Cardiovascular Health Disparities Research at Meharry Medical College
-
批准号:8289433
-
项目类别:
-
资助金额:$20.51万
-
财政年份:2011
-
负责人:John J. Murray
-
依托单位:
PARTICIPANT AND CLINICAL INTERACTIONS RESOURCE (PCIR)
-
批准号:8359880
-
项目类别:
-
资助金额:$42.7万
-
财政年份:2011
-
负责人:John J. Murray
-
依托单位:
Center for Cardiovascular Health Disparities Research at Meharry Medical College
-
批准号:8083231
-
项目类别:
-
资助金额:$20.51万
-
财政年份:2011
-
负责人:John J. Murray
-
依托单位:
MULTIDISCIPLINARY TRAINING AND CAREER DEVELOPMENT ACTIVITIES
-
批准号:8359876
-
项目类别:
-
资助金额:$11.93万
-
财政年份:2011
-
负责人:John J. Murray
-
依托单位:
MMC and VICC: Partnership for Survivorship (1 of 2)
-
批准号:8540359
-
项目类别:
-
资助金额:$19.4万
-
财政年份:2010
-
负责人:John J. Murray
-
依托单位:
MMC and VICC: Partnership for Survivorship (1 of 2)
-
批准号:8326219
-
项目类别:
-
资助金额:$13.73万
-
财政年份:2010
-
负责人:John J. Murray
-
依托单位:
MULTIDISCIPLINARY TRAINING AND CAREER DEVELOPMENT ACTIVITIES
-
批准号:8173600
-
项目类别:
-
资助金额:$12.1万
-
财政年份:2010
-
负责人:John J. Murray
-
依托单位:
PARTICIPANT AND CLINICAL INTERACTIONS RESOURCE (PCIR)
-
批准号:8173604
-
项目类别:
-
资助金额:$33.98万
-
财政年份:2010
-
负责人:John J. Murray
-
依托单位:
Meharry Medical College Minority-Based Community Clinical Oncology Program
-
批准号:8511579
-
项目类别:
-
资助金额:$28.6万
-
财政年份:2004
-
负责人:John J. Murray
-
依托单位:
Meharry Medical College Minority-Based Community Clinical Oncology Program
-
批准号:8308753
-
项目类别:
-
资助金额:$37.12万
-
财政年份:2004
-
负责人:John J. Murray
-
依托单位:
海外基金