ENERGETICS OF THE FAILING HEART

衰竭心脏的能量

基本信息

  • 批准号:
    6499038
  • 负责人:
  • 金额:
    $ 29.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-02-01 至 2004-01-31
  • 项目状态:
    已结题

项目摘要

The hypothesis that the failing heart is energy starved is both long-standing and controversial. There is now convincing evidence from both failed human myocardium and animal models of severe heart failure that the [ATP] is as much as approximately 25 percent lower than in normal myocardium. This decrease is due to a loss of the purine pool. Based on results using NMR spectroscopy and chemical assay, we and others have shown that the tissue contents of phosphocreatine (PCr) and creatine and the capacity of the CK reaction (Vmax) are also lower. These observations increase our understanding of two important aspects of cardiac energetics: the kinetics of ATP synthesis and the thermodynamics of ATP utilization, i.e. the chemical driving force for the ATP-consuming reactions. Our observations that the creatine and purine pools are lower in the failing heart have important implications for understanding the energetics of the failing heart. Because the concentrations of these substrates are lower, the velocities of the reactions they support must be lower. However, the driving force for ATPases of muscle contraction may not be compromised. This new information leads to the following hypothesis: that the loss of creatine in the failing myocardium is an important compensatory mechanism, preserving the driving force for the ATPase reactions. Little is known about the regulation of either creatine transport or de novo purine synthesis in the failing heart. Accordingly, the primary goal of the proposed research plan is to define the mechanisms whereby creatine and purine pools are depleted in the failing heart. A closely related goal is to manipulate the ATP/ADP and PCr/creatine ratios in normal and failing hearts (due to prolonged aortic banding in the rat), and in hearts with low CK Vmax caused by gene deletions of specific CK isozymes, to define the energetic state of the failing heart no longer capable of supporting normal contractile performance and contractile reserve.
心脏衰竭是能量匮乏的假设由来已久,也存在争议。现在,来自衰竭的人类心肌和严重心力衰竭的动物模型的令人信服的证据表明,[ATP]比正常心肌低约25%。这一下降是由于嘌呤池的损失。根据核磁共振波谱和化学分析的结果,我们和其他人发现,组织中磷酸肌酸(PCr)和肌酸的含量以及CK反应能力(Vmax)也较低。这些观察加深了我们对心脏能量学的两个重要方面的理解:ATP合成的动力学和ATP利用的热力学,即消耗ATP反应的化学驱动力。我们观察到衰竭心脏的肌酸和嘌呤水平较低,这对理解衰竭心脏的能量学有重要意义。因为这些底物的浓度较低,它们支持的反应速度肯定较低。然而,肌肉收缩的ATPase的驱动力可能不会受到影响。这一新信息导致了以下假设:衰竭心肌中肌酸的丢失是一种重要的代偿机制,保留了ATPase反应的驱动力。在衰竭的心脏中,肌酸转运或从头合成嘌呤的调节知之甚少。因此,拟议的研究计划的主要目标是确定衰竭心脏中肌酸和嘌呤池耗尽的机制。一个密切相关的目标是控制正常和衰竭心脏(由于大鼠主动脉缩窄延长所致)以及因特定CK同工酶基因缺失而导致CK Vmax降低的心脏的ATP/ADP和PCr/肌酸比值,以确定不再能够支持正常收缩性能和收缩储备的衰竭心脏的能量状态。

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 }}

JOANNE S INGWALL其他文献

JOANNE S INGWALL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('JOANNE S INGWALL', 18)}}的其他基金

ENERGY RESERVE IN THE FAILING MYOCARDIUM
衰竭心肌中的能量储备
  • 批准号:
    6564944
  • 财政年份:
    2002
  • 资助金额:
    $ 29.48万
  • 项目类别:
ENERGY RESERVE IN THE FAILING MYOCARDIUM
衰竭心肌中的能量储备
  • 批准号:
    6421861
  • 财政年份:
    2001
  • 资助金额:
    $ 29.48万
  • 项目类别:
ENERGETICS OF THE FAILING HEART
衰竭心脏的能量
  • 批准号:
    6039059
  • 财政年份:
    2000
  • 资助金额:
    $ 29.48万
  • 项目类别:
ENERGETICS OF THE FAILING HEART
衰竭心脏的能量
  • 批准号:
    6351604
  • 财政年份:
    2000
  • 资助金额:
    $ 29.48万
  • 项目类别:
ENERGY RESERVE IN THE FAILING MYOCARDIUM
衰竭心肌中的能量储备
  • 批准号:
    6302289
  • 财政年份:
    2000
  • 资助金额:
    $ 29.48万
  • 项目类别:
ENERGETICS OF THE FAILING HEART
衰竭心脏的能量
  • 批准号:
    6629056
  • 财政年份:
    2000
  • 资助金额:
    $ 29.48万
  • 项目类别:
INTRACELLULAR PH REGULATION IN ISCHEMIC MYOCARDIUM
缺血心肌细胞内 PH 值调节
  • 批准号:
    2028950
  • 财政年份:
    1997
  • 资助金额:
    $ 29.48万
  • 项目类别:
FUNCTIONAL PARAMETERS OF AGING
老化的功能参数
  • 批准号:
    6098443
  • 财政年份:
    1997
  • 资助金额:
    $ 29.48万
  • 项目类别:
INTRACELLULAR PH REGULATION IN ISCHEMIC MYOCARDIUM
缺血心肌细胞内 PH 值调节
  • 批准号:
    2717276
  • 财政年份:
    1997
  • 资助金额:
    $ 29.48万
  • 项目类别:
INTRACELLULAR PH REGULATION IN ISCHEMIC MYOCARDIUM
缺血心肌细胞内 PH 值调节
  • 批准号:
    2872907
  • 财政年份:
    1997
  • 资助金额:
    $ 29.48万
  • 项目类别:

相似海外基金

Adenosine triphosphate as a master variable for biomass in the oceanographic context
三磷酸腺苷作为海洋学背景下生物量的主变量
  • 批准号:
    2319114
  • 财政年份:
    2023
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Standard Grant
Characterizing the Interaction Between Adenosine Triphosphate and Pathological Alpha-synuclein Structures in Parkinson's Disease
表征帕金森病中三磷酸腺苷与病理性 α-突触核蛋白结构之间的相互作用
  • 批准号:
    565727-2021
  • 财政年份:
    2021
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Investigation of the development of pain during orthodontic tooth movement with adenosine triphosphate
三磷酸腺苷正畸牙齿移动过程中疼痛发生的研究
  • 批准号:
    20K18789
  • 财政年份:
    2020
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Neural Regulation of Adenosine Triphosphate (ATP) in the Nasal Mucosa
鼻粘膜三磷酸腺苷 (ATP) 的神经调节
  • 批准号:
    19K18793
  • 财政年份:
    2019
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
  • 批准号:
    460605-2014
  • 财政年份:
    2016
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Development of an Analytical Tool Utilizing Electrochemical Detection Methods For the Measuring of Protein Kinase Activity on a Protein Substrate Using Ferrocene-Adenosine Triphosphate (Fc-ATP) as a C
利用电化学检测方法开发分析工具,以二茂铁-三磷酸腺苷 (Fc-ATP) 作为 C,测量蛋白质底物上的蛋白激酶活性
  • 批准号:
    469948-2014
  • 财政年份:
    2016
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Vanier Canada Graduate Scholarship Tri-Council - Doctoral 3 years
Adenosine Triphosphate as a Signal for Evaluating Microbial Risk from Groundwater Supplies
三磷酸腺苷作为评估地下水供应微生物风险的信号
  • 批准号:
    507411-2016
  • 财政年份:
    2016
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Engage Grants Program
Development of an Analytical Tool Utilizing Electrochemical Detection Methods For the Measuring of Protein Kinase Activity on a Protein Substrate Using Ferrocene-Adenosine Triphosphate (Fc-ATP) as a C
利用电化学检测方法开发分析工具,以二茂铁-三磷酸腺苷 (Fc-ATP) 作为 C,测量蛋白质底物上的蛋白激酶活性
  • 批准号:
    469948-2014
  • 财政年份:
    2015
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Vanier Canada Graduate Scholarship Tri-Council - Doctoral 3 years
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
  • 批准号:
    460605-2014
  • 财政年份:
    2015
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Dynamics of the oxygen-dependent release of adenosine triphosphate from erythrocytes
红细胞氧依赖性三磷酸腺苷释放的动力学
  • 批准号:
    460605-2014
  • 财政年份:
    2014
  • 资助金额:
    $ 29.48万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Doctoral
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了