DYNAMICS OF CARDIAC ENERGY METABOLISM
心脏能量代谢动力学
基本信息
- 批准号:6280761
- 负责人:
- 金额:$ 1.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-02-18 至 1998-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The goal of this project is to understand the dynamic regulation
of cardiac energy metabolism and its effects on heart function in
cardiac disease, especially during hypertrophy culminating in heart
failure and during myocardial stunning. The time constant of the
phosphate metabolites determined with NMR spectroscopy during heart
rate steps (3 s) was shorter than the time constant of oxygen
consumption (11 s) in the same hearts. We hypothesized that this was
due to transitory glycolytic ATP production which delays transport and
explains the gap between the 3 and 11 s time constants and retards the
transfer of the energetic signal between sites of ATP consumption and
the mitochondria. Indeed, when glycolysis was inhibited and bypassed
by giving pyruvate as exogenous substrate both time constants became
short and the time constant of oxygen consumption was not
significantly different from the time constant of inorganic phosphate
and phosphocreatine. The time constant of oxygen consumption in
response to heart rate steps was also shortened when creatine kinase
was inhibited, suggesting that energetic buffering, not only by
glycolysis, but also by creatine kinase delays the energetic signal
between the sites of ATP consumption and the mitochondria. At 37
degrees Celsius 15 min of ischemia or hypoxia did lead to a
substantial increase in the mitochondrial time constant, indicating
that energy transfer and/or signaling between energy-consuming sites
and mitochondria is deteriorated in stunned myocardium. Reducing the
mitochondrial aerobic capacity by selective partial inhibition with
oligomycin did not lead to a slower response of oxidative
phosphorylation to heart rate steps, suggesting that transcytosolic
energy transport rather than mitochondrial processes determine the
adaptation speed of oxidative phosphorylation. We found that modest
arterial pressure overload for six weeks did not lead to a significant
increase in the response time of oxygen consumption, suggesting that
energy signaling between sites of ATP consumption and the mitochondria
is not yet impaired during mild cardiac hypertrophy.
该项目的目标是了解动态调节
心脏能量代谢及其对心功能的影响
心脏病,特别是在心脏肥大期间
衰竭和心肌顿抑期间。 的时间常数
心脏过程中用核磁共振波谱法测定磷酸盐代谢物
速率步长(3秒)比氧气的时间常数短
在相同的心中消耗(11秒)。 我们假设这是
由于短暂的糖酵解 ATP 产生延迟了运输和
解释了 3 秒和 11 秒时间常数之间的差距并延迟了
能量信号在 ATP 消耗位点之间的转移
线粒体。 事实上,当糖酵解被抑制和绕过时
通过给予丙酮酸作为外源底物,两个时间常数都变为
耗氧量时间常数不短
与无机磷酸盐的时间常数显着不同
和磷酸肌酸。 耗氧量时间常数
当肌酸激酶增加时,对心率步骤的反应也会缩短
被抑制,表明能量缓冲不仅通过
糖酵解,而且还通过肌酸激酶延迟能量信号
ATP 消耗位点和线粒体之间。 37岁
摄氏度 15 分钟的缺血或缺氧确实会导致
线粒体时间常数显着增加,表明
能源消耗站点之间的能量传输和/或信号传输
顿挫的心肌中线粒体受损。 减少
通过选择性部分抑制线粒体有氧能力
寡霉素不会导致氧化反应减慢
磷酸化对心率步骤的影响,表明跨胞质
能量运输而不是线粒体过程决定了
氧化磷酸化的适应速度。 我们发现,谦虚的
六周的动脉压超负荷并未导致显着的
耗氧量的响应时间增加,表明
ATP 消耗位点和线粒体之间的能量信号传导
在轻度心脏肥大期间尚未受损。
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)
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{{ truncateString('JOHANNES H VAN BEEK', 18)}}的其他基金
LOCAL RATE OF MYOCARDIAL AEROBIC METABOLIC IN RELATION TO LOCAL BLOOD FLOW
心肌有氧代谢的局部速率与局部血流量的关系
- 批准号:
6119783 - 财政年份:1998
- 资助金额:
$ 1.02万 - 项目类别: