Elevated intracellular Na (Na_i) and metabolic impairment are interrelated pathophysiological features of the failing heart (HF). There have been a number of studies showing that myocardial sodium elevation subtly affects mitochondrial function. During contraction, mitochondrial calcium (Ca_mito) stimulates a variety of TCA cycle enzymes, thereby providing reducing equivalents to maintain ATP supply. Na_i elevation has been shown to impact Ca_mito; however, whether metabolic remodelling in HF is caused by increased Na_i has only been recently demonstrated. This novel insight may help to elucidate the contribution of metabolic remodelling in the pathophysiology of HF, the lack of efficacy of current HF therapies and a rationale for the development of future metabolism-targeting treatments. Here we review the relationship between Na pump inhibition, elevated Na_i, and altered metabolic profile in the context of HF and their link to metabolic (in)flexibility and mitochondrial reprogramming.

升高的细胞内 Na (Na _i ) 和代谢障碍是心力衰竭 (HF) 的相互关联的病理生理特征。已有多项研究表明，心肌钠升高会微妙地影响线粒体功能。在收缩过程中，线粒体钙 (Ca _mito ) 会刺激多种 TCA 循环酶，从而提供还原当量以维持 ATP 供应。Na _i升高已被证明会影响 Ca _mito；然而，HF 中的代谢重塑是否是由 Na _{i增加引起的}只是最近才被证明。这一新见解可能有助于阐明代谢重塑在 HF 病理生理学中的作用、当前 HF 疗法缺乏疗效以及开发未来代谢靶向治疗的基本原理。在这里，我们回顾了在 HF 的情况下 Na 泵抑制、升高的 Na _i和改变的代谢特征之间的关系，以及它们与代谢（不）灵活性和线粒体重编程的联系。