Radionuclide imaging of myocardial metabolism.
Radionuclide imaging of myocardial metabolism.
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DOI：
10.1161/circimaging.109.860593
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Gropler RJ
中科院分区：
文献类型：
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作者：
Peterson LR;Gropler RJ
心脏健康取决于心脏利用不同底物来支持整体氧化代谢以产生ATP的能力。事实上，底物偏好的可塑性丧失是多种心脏病的特征，如脂肪酸代谢占主导地位的糖尿病性心脏病和葡萄糖代谢占主导地位的扩张型心肌病。由于心肌底物代谢的多效性作用，底物偏好可塑性的丧失可能产生的有害影响远远超出能量产生的损害，包括各种细胞信号传导途径的扰动，细胞生长的改变和细胞存活率的降低，尽管我们对心肌代谢改变和心脏病之间关系的理解迅速增长，但仍存在许多重要问题。例如，心肌基质使用变化的关键决定因素是什么？当这些变化确实发生时，它们在多大程度上是适应性的，或者有变得不适应的倾向？这些代谢模式是否具有预后意义？尽管针对心肌底物使用的重要方面的转基因模型提供了对各种心脏疾病中心肌代谢-功能关系的机械见解，但所观察到的表型与相应的人类状况的相关性通常不清楚。同样地，应用基因组学已经鉴定了许多密切参与心肌底物使用调节的基因变异，但鉴定所有临床相关的遗传变异仍然是难以捉摸的。因此，对心肌基质代谢的准确无创成像方法的需求不断增长，这些方法提供了工作台和床边之间的联系。在这方面，放射性核素方法起了带头作用。临床适用性的最显著的例子是用正电子发射断层扫描（PET）和18F-氟代右旋糖（FDG）检测缺血但存活的心肌，用于治疗缺血性心肌病患者。在随后的讨论中，使用放射性核素方法的代谢成像的进展及其在心血管疾病研究中的潜在未来应用进行了讨论。
Cardiac health is dependent on the heart’s ability to utilize different substrates to support overall oxidative metabolism to generate ATP. Indeed, a loss in plasticity in substrate preference is characteristic of a variety cardiac diseases such as diabetic heart disease, in which fatty acid metabolism predominates, and dilated cardiomyopathy, in which glucose metabolism predominates. Because of the pleiotropic actions of myocardial substrate metabolism, a loss in plasticity in substrate preference can have detrimental effects well beyond impairment of energy production, including perturbations in various cell signaling pathways, alterations in cell growth, and decreased cell survival.Despite the rapid growth in our understanding of the relationship between altered myocardial metabolism and cardiac disease, many important questions remain. For example, what are the key determinants of changes in myocardial substrate use? When these changes do occur, to what extent are they adaptive or have the propensity to become maladaptive? And are these metabolic patterns of prognostic significance? Although transgenic models targeting vital aspects of myocardial substrate use are providing mechanistic insights into myocardial metabolic-functional relationships in various cardiac diseases, the relevance of the observed phenotypes to the corresponding human condition is frequently unclear. Likewise, applied genomics have identified numerous gene variants intimately involved in the regulation of myocardial substrate use, yet identifying all clinically relevant genetic variants remains elusive. As a consequence, there is an ever-growing demand for accurate noninvasive imaging approaches of myocardial substrate metabolism that provide links between the bench and the bedside. In this regard, radionuclide approaches have led the way. The most notable example of clinical applicability is the detection of ischemic but viable myocardium with positron emission tomography (PET) and 18F-fluorodexoglucose (FDG) for the treatment of patients with ischemic cardiomyopathy. In the subsequent discussion, advances in metabolic imaging using radionuclide approaches and their potential future applications in the study of cardiovascular disease are discussed.