Nie Yuxin, Lin Liyu, Yang Qiang, Hu Jiachang, Sun Minmin, Xiang Fangfang, Cao Xuesen, Yu Jinbo, Wang Yaqiong, Teng Jie, Ding Xiaoqiang, Shen Bo, Zhang Zhen
Department of Nephrology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China.
Shanghai Key Laboratory of Kidney and Blood Purification, No. 180 Fenglin Road, Shanghai 200032, China.
Biomedicines. 2024 Oct 20;12(10):2402. doi: 10.3390/biomedicines12102402.
: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K) and calcium (Ca) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoK) in mitigating HIMS. : A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoK channel modulators were evaluated by administering diazoxide (DZX), a mitoK opener, and 5-hydroxydecanoate (5-HD), a mitoK blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca levels. Myocardial function was evaluated using speckle tracking echocardiography. : Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K and Ca concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. : Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoK channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.
血液透析诱导的心肌顿抑（HIMS）是维持性血液透析患者常见的并发症，其特征是由于缺血发作导致短暂的左心室功能障碍。线粒体功能障碍以及钾（K）和钙（Ca）等关键离子的波动与HIMS的发病机制有关。本研究旨在探讨线粒体功能障碍的作用以及线粒体ATP敏感性钾通道（mitoK）在减轻HIMS方面的保护潜力。
建立5/6肾切除大鼠模型以模拟慢性肾病及随后的HIMS。在血液透析前，通过给予mitoK开放剂二氮嗪（DZX）和mitoK阻滞剂5-羟基癸酸（5-HD）来评估mitoK通道调节剂的作用。通过测量膜电位、ATP合酶活性和线粒体内钙水平来评估线粒体功能。使用斑点追踪超声心动图评估心肌功能。
接受血液透析的大鼠左心室应变和同步性显著降低。与对照组相比，给予DZX可显著改善线粒体功能并降低心肌应变。相反，5-HD使线粒体肿胀恶化并破坏心肌功能。透析液中较高的K和Ca浓度与改善的线粒体能量代谢和心肌应变相关。
血液透析期间的线粒体功能障碍和离子失衡是HIMS的关键因素。mitoK通道的激活提供线粒体保护，并可能作为减轻HIMS的潜在治疗策略。
