Department of Physiology, Anatomy and Genetics, University of Oxford, UK.
Department of Physiology, Anatomy and Genetics, University of Oxford, UK; Oxford Centre for Clinical Magnetic Resonance Research, John Radcliffe Hospital, Oxford, UK; Clarendon Laboratory, Department of Physics, University of Oxford, UK.
Prog Nucl Magn Reson Spectrosc. 2018 Jun-Aug;106-107:66-87. doi: 10.1016/j.pnmrs.2018.05.002. Epub 2018 May 31.
Cardiovascular disease is the leading cause of death world-wide. It is increasingly recognised that cardiac pathologies show, or may even be caused by, changes in metabolism, leading to impaired cardiac energetics. The heart turns over 15 times its own weight in ATP every day and thus relies heavily on the availability of substrates and on efficient oxidation to generate this ATP. A number of old and emerging drugs that target different aspects of metabolism are showing promising results with regard to improved cardiac outcomes in patients. A non-invasive imaging technique that could assess the role of different aspects of metabolism in heart disease, as well as measure changes in cardiac energetics due to treatment, would be valuable in the routine clinical care of cardiac patients. Hyperpolarised magnetic resonance spectroscopy and imaging have revolutionised metabolic imaging, allowing real-time metabolic flux assessment in vivo for the first time. In this review we summarise metabolism in the healthy and diseased heart, give an introduction to the hyperpolarisation technique, 'dynamic nuclear polarisation' (DNP), and review the preclinical studies that have thus far explored healthy cardiac metabolism and different models of human heart disease. We furthermore show what advances have been made to translate this technique into the clinic, what technical challenges still remain and what unmet clinical needs and unexplored metabolic substrates still need to be assessed by researchers in this exciting and fast-moving field.
心血管疾病是全球范围内的主要死亡原因。人们越来越认识到,心脏病理学表现出或甚至可能由代谢变化引起,导致心脏能量代谢受损。心脏每天的 ATP 周转率是其自身重量的 15 倍,因此严重依赖底物的可用性和有效的氧化作用来产生这种 ATP。一些针对代谢不同方面的旧药和新药在改善患者心脏预后方面显示出有希望的结果。一种非侵入性的成像技术,可以评估不同代谢方面在心脏病中的作用,并测量由于治疗而导致的心脏能量代谢的变化,这将在心脏患者的常规临床护理中具有重要价值。极化磁共振波谱和成像技术彻底改变了代谢成像,首次能够实时评估体内的代谢通量。在这篇综述中,我们总结了健康和患病心脏中的代谢,介绍了极化技术“动态核极化”(DNP),并回顾了迄今为止探索健康心脏代谢和不同类型人类心脏病模型的临床前研究。我们还展示了将这项技术转化为临床应用的进展,仍然存在哪些技术挑战,以及在这个令人兴奋和快速发展的领域中,仍有哪些未满足的临床需求和未探索的代谢底物需要研究人员进行评估。