ENERGETICS OF HIBERNATING MYOCARDIUM

冬眠心肌的能量

• 批准号: 3083445
• 负责人: ANDREW E ARAI
• 金额: $ 7.56万
• 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/3083445
• 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 产量）必须等于做功率（ATP 水解或 ATP 消耗）。在 60 分钟的稳定轻度心肌缺血期间，一种新的 ATP 消耗率与血流限制 ATP 之间的平衡 生产是以区域收缩减少为代价来实现的 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。 这笔赠款的目标是定义细胞调节 线粒体 ATP 产生（ADP、无机磷酸盐、磷酸化 电位、氧化还原态、镁、肌红蛋白氧合、F1-F0-ATP 合成酶活性）和心肌 ATP 消耗（肌原纤维工作， 细胞内钙代谢）作为对轻度的代谢适应 发生缺血。我们将使用体内 31P NMR 的组合 光谱学、1H 磁共振成像、光学光谱学和 心肌活检技术。 这需要进一步的发展和 心肌快速磁共振成像技术的验证 氧合。钙瞬变幅度和心肌的评估 能量学将检验心肌钙水平的假设 调节区域收缩功能和 ATP 产生 长时间轻度缺血。新型正性肌力药物的作用 （以 EMD 57033 为代表）应该有助于描述钙在 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。这 腺苷对心肌 ATP 含量的影响将有助于确定 轻度缺血期间 ATP 产生和消耗之间的平衡。这 这些最先进方法的应用应该增强我们的 了解心肌灌注不足的临床常见状态，例如 就像冬眠的心肌一样。