Comprehensive Heart Failure Center, University and University Hospital Würzburg, Würzburg, Germany.
Department of Internal Medicine I, University Hospital Würzburg, Oberdürrbacher Straße 6, Haus A3, 97080, Würzburg, Germany.
Sci Rep. 2024 Jan 29;14(1):2426. doi: 10.1038/s41598-024-52377-w.
Cardiac myocyte sodium (Na) homoeostasis is pivotal in cardiac diseases and heart failure. Intracellular Na ([Na]) is an important regulator of excitation-contraction coupling and mitochondrial energetics. In addition, extracellular Na ([Na]) and its water-free storage trigger collagen cross-linking, myocardial stiffening and impaired cardiac function. Therefore, understanding the allocation of tissue Na to intra- and extracellular compartments is crucial in comprehending the pathophysiological processes in cardiac diseases. We extrapolated [Na] using a three-compartment model, with tissue Na concentration (TSC) measured by in vivo Na-MRI, extracellular volume (ECV) data calculated from T1 maps, and [Na] measured by in vitro fluorescence microscopy using Na binding benzofuran isophthalate (SBFI). To investigate dynamic changes in Na compartments, we induced pressure overload (TAC) or myocardial infarction (MI) via LAD ligation in mice. Compared to SHAM mice, TSC was similar after TAC but increased after MI. Both TAC and MI showed significantly higher [Na] compared to SHAM (around 130% compared to SHAM). Calculated [Na] increased after MI, but not after TAC. Increased TSC after TAC was primarily driven by increased [Na], but the increase after MI by elevations in both [Na] and [Na].
心肌细胞钠 (Na) 稳态在心脏疾病和心力衰竭中至关重要。细胞内 Na ([Na]) 是兴奋-收缩偶联和线粒体能量学的重要调节剂。此外,细胞外 Na ([Na]) 及其无水储存会引发胶原蛋白交联、心肌僵硬和心脏功能受损。因此,了解组织 Na 向细胞内外室的分配对于理解心脏疾病中的病理生理过程至关重要。我们使用三腔模型推断 [Na],通过体内 Na-MRI 测量组织 Na 浓度 (TSC),通过 T1 图谱计算细胞外容积 (ECV) 数据,并通过体外荧光显微镜使用 Na 结合苯并呋喃异酞酸盐 (SBFI) 测量 [Na]。为了研究 Na 隔室的动态变化,我们通过在小鼠中结扎 LAD 诱导压力超负荷 (TAC) 或心肌梗死 (MI)。与 SHAM 小鼠相比,TAC 后 TSC 相似,但 MI 后增加。TAC 和 MI 与 SHAM 相比,[Na] 均显著升高(比 SHAM 高约 130%)。MI 后计算的 [Na] 增加,但 TAC 后没有增加。TAC 后 TSC 的增加主要是由于 [Na] 的增加引起的,但 MI 后则是由于 [Na] 和 [Na] 的升高引起的。
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