CONTRACTILE FORCE AND CALCIUM HANDLING IN HEART FAILURE
CONTRACTILE FORCE AND CALCIUM HANDLING IN HEART FAILURE
批准号:
2378820
负责人:
Pieter P. de TOMBE
金额:
$6.81万
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-06-01 至 1999-02-28
中文摘要
充血性心力衰竭与心肌细胞受损有关
功能。其含量和异构体分布的变化
参与钙离子转运的收缩蛋白和关键蛋白有
在瑞士法郎被发现。因此,充血性心力衰竭的力量发展可能减少。
由于钙处理的改变或由于收缩蛋白的减少
功能。有关充血性心力衰竭患者钙离子处理的结果相互矛盾
这可能是由于所用方法的不确定性所致
测量细胞内钙离子。同样,收缩蛋白是否
CHF的功能受损也是不确定的,因为肌节长度
未被测量和控制的。因此,这些变化之间的关系
充血性心力衰竭时蛋白质合成和心肌细胞功能受损
不确定。关于细胞过程的准确知识
参与CHF的发展对CHF的发展至关重要
旨在抗击慢性心力衰竭的创新战略。当前的总目标
研究建议是确定心肌细胞减少的机制
充血性心力衰竭实验动物模型中的力量发育。这个
我们将使用的实验动物模型是左旋门冬氨酸诱导的大鼠心力衰竭。
室性心肌梗死。这些小的右室
啮齿动物可以提供足够薄和均匀的小梁。
为了允许i)在肌节水平上进行最先进的机械研究,
以及ii)细胞内钙离子的精确校准测量。
初步数据表明,使用该模型的功能受到抑制。
终末期充血性心力衰竭时孤立的右室小梁。具体来说,我们
将检验这一假设,即减少心肌力的发展
慢性心力衰竭的发生是由以下因素引起的:
1)收缩时细胞内钙离子浓度降低。
小梁细胞内钙离子将通过以下方法直接测量
荧光钙探针。为了获得明确的数据,体内
将使用INDO-1的游离盐进行校准,介绍
通过一种最新开发的技术进入胞洛尔。
2)降低了最大力量发展或钙反应
收缩装置。力的发展将以渗透性来衡量
骨小梁作为游离钙的功能。激光衍射技术将
用于准确测量和控制肌节长度,以便
获得了准确和明确的数据。
英文摘要
Congestive heart failure (CHF) is associated with impaired myocardial cell
function. Alterations in the content and isoform distribution of
contractile proteins and key proteins involved in calcium handling have
been found in CHF. Thus, decreased force development in CHF may result
from altered calcium handling or from reduced contractile protein
function. Conflicting results regarding calcium handling in CHF have been
obtained, which may be due to uncertainties with the methods used to
measure intracellular calcium. Likewise, whether contractile protein
function is impaired in CHF is also uncertain because sarcomere length was
not measured and controlled. Thus, the relationship between alterations in
protein synthesis and impaired myocardial cell function in CHF is still
uncertain. Accurate knowledge regarding the cellular processes that
participate in the development of CHF is critical to the development of
innovative strategies aimed to combat CHF. The overall goal of the present
research proposal is to determine the mechanism of reduced myocardial
force development in an experimental animal model of CHF. The
experimental animal model that we will use is CHF in rats, induced by left
ventricular myocardial infarction. The right ventricles of these small
rodents can provide trabeculae that are sufficiently thin and homogenous
to allow i) state of art mechanical studies at the level of the sarcomere,
and ii) accurate calibrated measurements of intracellular calcium.
Preliminary data, using this model, indicate depressed function of
isolated right ventricular trabeculae at end-stage CHF. Specifically we
will test the hypothesis that reduced myocardial force development during
the development of CHF is caused by:
1) Reduced intracellular calcium concentration during systole.
Intracellular calcium will be measured directly in trabeculae by
fluorescence calcium probe. To obtain unambiguous data, in-vivo
calibration will be obtained by using the free salt of Indo-1, introduced
into the cytolol by a recently developed technique.
2) Reduced maximum force development or calcium responsiveness of the
contractile apparatus. Force development will be measured in permeabilized
trabeculae as function of free calcium. Laser diffraction techniques will
be used to accurately measure and control sarcomere length such that
accurate and unambiguous data are obtained.
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会议论文
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:8361264
-
项目类别:
-
资助金额:$2.97万
-
财政年份:2011
-
负责人:Pieter P. de TOMBE
-
依托单位:
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:8168608
-
项目类别:
-
资助金额:$1.44万
-
财政年份:2010
-
负责人:Pieter P. de TOMBE
-
依托单位:
Molecular Mechanisms of Myofilament Dysfunction in Heart Failure
-
批准号:7919147
-
项目类别:
-
资助金额:$38.8万
-
财政年份:2010
-
负责人:Pieter P. de TOMBE
-
依托单位:
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:7954890
-
项目类别:
-
资助金额:$6.74万
-
财政年份:2009
-
负责人:Pieter P. de TOMBE
-
依托单位:
Myosin Binding Protein C structure-function relationships in the failing heart
-
批准号:7860821
-
项目类别:
-
资助金额:$35.61万
-
财政年份:2009
-
负责人:Pieter P. de TOMBE
-
依托单位:
Myosin Binding Protein C structure-function relationships in the failing heart
-
批准号:7937867
-
项目类别:
-
资助金额:$34.66万
-
财政年份:2009
-
负责人:Pieter P. de TOMBE
-
依托单位:
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:7722741
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项目类别:
-
资助金额:$5.06万
-
财政年份:2008
-
负责人:Pieter P. de TOMBE
-
依托单位:
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:7601738
-
项目类别:
-
资助金额:$5.87万
-
财政年份:2007
-
负责人:Pieter P. de TOMBE
-
依托单位:
Molecular Mechanisms of Myofilaments Dysfunction in Heart Function
-
批准号:7459534
-
项目类别:
-
资助金额:$35.79万
-
财政年份:2007
-
负责人:Pieter P. de TOMBE
-
依托单位:
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:7369132
-
项目类别:
-
资助金额:$0.89万
-
财政年份:2006
-
负责人:Pieter P. de TOMBE
-
依托单位:
Molecular Mechanisms of Myofilaments Dysfunction in Heart Function
-
批准号:7440999
-
项目类别:
-
资助金额:$33.61万
-
财政年份:2006
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:8320624
-
项目类别:
-
资助金额:$7.36万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:8305568
-
项目类别:
-
资助金额:$43.99万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:7901601
-
项目类别:
-
资助金额:$37.03万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:7752761
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项目类别:
-
资助金额:$38.28万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:7807658
-
项目类别:
-
资助金额:$31.82万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:8112749
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项目类别:
-
资助金额:$37.02万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:6987535
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项目类别:
-
资助金额:$35.45万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
TIME-RESOLVED X-RAY DIFFRACTION OF CARDIAC MUSCLE
-
批准号:7182099
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项目类别:
-
资助金额:$0.59万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
Frank-Starling's Law of the Heart: Cellular Mechanisms
-
批准号:7258819
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项目类别:
-
资助金额:$32.31万
-
财政年份:2005
-
负责人:Pieter P. de TOMBE
-
依托单位:
海外基金