GUT ISCHEMIA & MOF SYNDROME--MICROVASCULAR TRANSDUCTION
GUT ISCHEMIA & MOF SYNDROME--MICROVASCULAR TRANSDUCTION
批准号:
2138678
负责人:
Gregory B. Bulkley
金额:
$24.93万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1983
资助国家:
美国
项目状态:
已结题
起止时间:
1983-01-01 至 1995-12-31
关键词:
cardiogenic shock cardiovascular disorder chemotherapy cardiovascular disorder diagnosis creatine kinase disease /disorder model endotoxins enteritis free radical oxygen gastrointestinal circulation gastrointestinal circulatory insufficiency gastrointestinal disorder diagnosis gastrointestinal imaging /visualization human subject intestine disorder ischemia laboratory rat multiple organ failure orphan disease /drug pancreatitis radionuclide imaging /scanning radiotracer renin angiotensin system reperfusion swine vasopressins xanthine oxidase
中文摘要
外科手术、输血治疗、急诊和
英文摘要
Improvements in surgery, transfusion therapy, emergency and
intensive care have generated increasing numbers of patients who
initially survive resuscitation from circulatory (hypovolemic and
cardiogenic) shock, only to succumb later from the multiple organ failure
synidrome (MOF). Having previously defined the hemodynamic mechanism,
and a major toxic pathway by which splanchnic organs (intestine, colon,
stomach, and liver) are targets for ischemia and reperfusion injury
during shock, this project now seeks to better understand the mechanisms
by which these injured splanchnic organs influence injury in distant
(non-splanchnic) organs in a porcine model of MOF.
Specific hypotheses to be evaluated include: a) The intestine and/or
pancreas are sources of important circulating toxins, some of which have
proteolytic activity. b) The microvascular endothelial cell is an
important initial target of these mediators; c) Toxic oxygen metabolites
generated by xanthine oxidase (XO), activated by these circulating toxins
from xanthine dehydrogenase (XD) on the endothelial cell surface, are the
initial trigger of this microvascular injury. This hypothesis is based
upon the exciting new finding that enzymatically active and
immunoreactive XO is present in high concentration on the outside surface
of the EC plasma membrane. d) Neutrophil accumulation in the
microvasculature, with its own important toxic consequences, is secondary
to this primary endothelial cell injury.
In porcine in situ, porcine cross circulation, and ex situ perfused
organ (porcine lung and rat liver), and mouse reticuloendothelial
function preparations, and in cultured endothelial monolayers, these
hypotheses will be tested by probing with proteases (chymotrypsin)
antiproteases (soybean trypsin inhibitor), specific antioxidants
(superoxide dismutuse and catalase) and xanthine oxidase inhibition both
with allopurinol and with a new monoclonal antibody that blocks XO
activity. Endothelial XO will be quantitatively distinguished from XD in
situ by a new histochemical method, and by MoAb's that distinguish XO
from XD. These methods should allow us to evaluate the central
hypothesis, that endothelial cell plasma membrane surface xanthine
oxidoreductase, via post-translational XD to XO conversion, transduces
circulating toxic and inflammatory mediators into the end organ injury
that constitutes multiple organ failure.
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会议论文
BASIC SCIENTIFIC TRAINING FOR GASTROINTESTINAL SURGEONS
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批准号:2135377
-
项目类别:
-
资助金额:$3.77万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
BASIC SCIENTIFIC TRAINING FOR GASTROINTESTINAL SURGEONS
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批准号:6176309
-
项目类别:
-
资助金额:$13.91万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
Basic Scientific Training for Gastrointestinal Surgeons
-
批准号:6516900
-
项目类别:
-
资助金额:$17.27万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
BASIC SCIENTIFIC TRAINING FOR GASTROINTESTINAL SURGEONS
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批准号:2733917
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项目类别:
-
资助金额:$11.28万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
BASIC SCIENTIFIC TRAINING FOR GASTROINTESTINAL SURGEONS
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批准号:2905118
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项目类别:
-
资助金额:$13.83万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
Basic Scientific Training for Gastrointestinal Surgeons
-
批准号:6661161
-
项目类别:
-
资助金额:$17.05万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
Basic Scientific Training for Gastrointestinal Surgeons
-
批准号:6352089
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项目类别:
-
资助金额:$14.91万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
BASIC SCIENTIFIC TRAINING FOR GASTROINTESTINAL SURGEONS
-
批准号:2443857
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项目类别:
-
资助金额:$7.53万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
Basic Scientific Training for Gastrointestinal Surgeons
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批准号:6804445
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项目类别:
-
资助金额:$17.06万
-
财政年份:1996
-
负责人:Gregory B. Bulkley
-
依托单位:
Basic Scientific Training for Gastrointestinal Surgeons
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批准号:6662397
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项目类别:
-
资助金额:$1.23万
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财政年份:1996
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负责人:Gregory B. Bulkley
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依托单位:
OXIDANT SIGNALLING IN THE ENTEROHEPATIC MICROVASCULATURE
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批准号:6517050
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项目类别:
-
资助金额:$30.15万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
GUT ISCHEMIA & MOF SYNDROME: MICROVASCULAR TRANSDUCTION
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批准号:3230297
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项目类别:
-
资助金额:$23.51万
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财政年份:1983
-
负责人:Gregory B. Bulkley
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依托单位:
INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS
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批准号:3230301
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项目类别:
-
资助金额:$21.04万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS
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批准号:3230296
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项目类别:
-
资助金额:$21.51万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS
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批准号:3230299
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项目类别:
-
资助金额:$17.58万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS
-
批准号:3230300
-
项目类别:
-
资助金额:$20.22万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
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依托单位:
SIGNAL TRANSDUCTION BY ENDOTHELIAL XANTHINE OXIDASE
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批准号:2856720
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项目类别:
-
资助金额:$29.16万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
SIGNAL TRANSDUCTION BY ENDOTHELIAL XANTHINE OXIDASE
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批准号:2634193
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项目类别:
-
资助金额:$30.9万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
SIGNAL TRANSDUCTION BY ENDOTHELIAL XANTHINE OXIDASE
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批准号:2138680
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项目类别:
-
资助金额:$33.83万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位:
INTESTINAL ISCHEMIA: PATHOPHYSIOLOGY AND DIAGNOSIS
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批准号:3152339
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项目类别:
-
资助金额:$15.23万
-
财政年份:1983
-
负责人:Gregory B. Bulkley
-
依托单位: