Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning

• Published in: Biomedicines 2024-10, Vol.12 (10), p.2402
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Analysis; Animals; ATP synthase; Biomarkers; Calcium (mitochondrial); Calcium channels; Calcium metabolism; Cardiac function; Care and treatment; Carotid arteries; Catheters; chronic kidney disease; Chronic kidney failure; Complications and side effects; Creatinine; Dialysate; Echocardiography; Energy metabolism; Heart; Hemodialysis; Ischemia; Kidney diseases; Medical prognosis; Membrane potential; Mitochondria; Mitochondrial diseases; mitochondrial dysfunction; Mortality; myocardial stunning; Nephrectomy; Patient outcomes; Peritoneal dialysis; Potassium channels; Prevention; Risk factors; Veins & arteries; Venous access; Ventricle
• ISSN: 2227-9059; 2227-9059
• 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.