ENERGETICS OF HIBERNATING MYOCARDIUM

冬眠心肌的能量

• 批准号: 2211187
• 负责人: ANDREW E ARAI
• 金额: $ 7.02万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2211187
• 关键词: adenosine; adenosine triphosphate; bioenergetics; calcium flux; calcium metabolism; cardiotonic agents; coronary vessels; fluorescence spectrometry; heart circulation; heart metabolism; heart pharmacology; hibernation; hydrogen transporting ATP synthase; myocardial ischemia /hypoxia; myocardium; nuclear magnetic resonance spectroscopy; oxidation reduction reaction; oxidative phosphorylation; respiratory oxygenation; swine

In a steady state, the rate of myocardial energy conversion (ATP production) must equal the rate of work (ATP hydrolysis or ATP consumption). During 60 minutes of steady mild myocardial ischemia, a new balance between the rate of ATP consumption and blood-flow-limited ATP production is achieved at the expense of reduced regional contractile function. These adaptations to mild ischemia appear to define the pathophysiology of the hibernating myocardium. The goal of this grant is to define the cellular regulation of mitochondrial ATP production (ADP, inorganic phosphate, phosphorylation potential, redox state, magnesium, myoglobin oxygenation, F1-F0-ATP synthase activity) and myocardial ATP consumption (myofibrillar work, intracellular calcium metabolism) as metabolic adaptations to mild ischemia develop. We will use a combination of in vivo 31P NMR spectroscopy, 1H magnetic resonance imaging, optical spectroscopy, and myocardial biopsy techniques. This will require further development and validation for rapid magnetic resonance imaging techniques of myocardial oxygenation. The assessment of calcium transient amplitudes and myocardial energetics will test the hypothesis that myocardial calcium levels regulate both regional contractile function and ATP production during prolonged mild ischemia. The effects of a new class of inotropic agents (typified by EMD 57033) should help delineate the role of calcium in the pathophysiology of hibernating myocardium as well as the metabolic and functional consequences of these agents on ischemic myocardium. The effects of adenosine on myocardial ATP content will help define the balance between ATP production and consumption during mild ischemia. The application of these state-of-the-art methodologies should enhance our understanding of clinically common states of myocardial hypoperfusion such as the hibernating myocardium.

在稳定状态下，心肌能量转换率（ATP 生产）必须等于工作速率（ATP水解或ATP 消费）。在60分钟的稳定轻度心肌缺血期间， ATP消耗率与血流受限ATP之间的平衡 生产是以减少区域收缩为代价的， 功能这些对轻度缺血的适应似乎定义了 冬眠心肌的病理生理学。 这项资助的目标是确定细胞的调节， 线粒体ATP生成（ADP，无机磷酸盐，磷酸化 电位，氧化还原状态，镁，肌红蛋白氧合，F1-F0-ATP 合成酶活性）和心肌ATP消耗（肌原纤维功， 细胞内钙代谢）作为代谢适应轻度 局部缺血发生。我们将结合使用体内31 P NMR 光谱学、1H磁共振成像、光谱学和 心肌活检技术。 这需要进一步发展， 心肌快速磁共振成像技术的验证 氧合钙瞬变幅度与心肌缺血的关系 能量学将检验心肌钙水平 调节局部收缩功能和ATP的产生， 长期轻度缺血一类新的正性肌力药的作用 （以EMD 57033为代表）应有助于描述钙在 冬眠心肌的病理生理学以及代谢和 这些药物对缺血心肌的功能影响。的 腺苷对心肌ATP含量的影响将有助于确定 在轻度缺血期间ATP产生和消耗之间的平衡。的 这些最先进的方法的应用应该提高我们的 了解心肌灌注不足的临床常见状态， 就像冬眠的心肌一样