ENERGETICS OF HIBERNATING MYOCARDIUM

在稳态下，心肌能量转换率(ATP) 生产)必须等于工作速度(ATP水解或ATP 消费)。在稳定的轻度心肌缺血60分钟内，一种新的 三磷酸腺苷消耗率与血流受限三磷酸腺苷的平衡 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。 这项拨款的目标是定义细胞调节 线粒体ATP产生(ADP、无机磷、磷酸化 电位，氧化还原状态，镁，肌红蛋白氧合，F1-F0-ATP 合酶活性)和心肌ATP消耗(肌原纤维做功， 细胞内钙代谢)作为对轻度的代谢适应 就会发展成缺血。我们将使用体内31P核磁共振的组合 光谱学、1H磁共振成像、光学光谱学和 心肌活检技术。这将需要进一步的发展和 心肌快速磁共振成像技术的验证 氧合作用。钙瞬变波幅与心肌的关系 能量学将检验这样的假设：心肌钙水平 同时调节局部收缩功能和ATP的产生 持续轻度缺血。一类新型正性肌力药的作用 (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及代谢和 这些药物对缺血心肌的功能后果。这个 腺苷对心肌ATP含量的影响将有助于确定 轻度缺血时ATP的产生和消耗之间的平衡。这个 应用这些最先进的方法应该会增强我们的 对临床常见心肌低灌注状态的认识 作为冬眠的心肌。

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.