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. 2024 Oct 20;12(10):2402.
doi: 10.3390/biomedicines12102402.

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

Yuxin Nie  1   2 , Liyu Lin  1   2   3   4 , Qiang Yang  1   2 , Jiachang Hu  1   2 , Minmin Sun  5   6 , Fangfang Xiang  1   2 , Xuesen Cao  1   2 , Jinbo Yu  1   2 , Yaqiong Wang  1   2 , Jie Teng  1   2   3   4 , Xiaoqiang Ding  1   2   3   4 , Bo Shen  1   2 , Zhen Zhang  1   2
Affiliations

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

Yuxin Nie et al. Biomedicines. .

Abstract

Background/Objectives: 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 (Ca2+) 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 (mitoKATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoKATP channel modulators were evaluated by administering diazoxide (DZX), a mitoKATP opener, and 5-hydroxydecanoate (5-HD), a mitoKATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca2+ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: 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 Ca2+ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoKATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.

Keywords: chronic kidney disease; hemodialysis; mitochondrial dysfunction; myocardial stunning.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Hemodialysis and echocardiographic monitoring in rats.
Figure 2
Figure 2
Two-dimensional speckle tracking shows a decrease in left ventricular strain values before (A) and immediately after (B) dialysis.
Figure 3
Figure 3
Effects of K+ and Ca2+ concentrations on mitochondrial energy metabolism. DZX (diazoxide), mitoKATP channel opener; 5HD (5-hydroxydecanoate), mitoKATP channel blocker; CCB (nicardipine), calcium channel blocker; JC-1, mitochondrial membrane potential assay; H-ATP, ATP synthase activity; Ca2+, intramitochondrial Ca2+ concentration. No between-group differences regarding mitochondrial membrane potential, mitochondrial ATP synthase activity, and mitochondrial Ca2+ were observed.
Figure 4
Figure 4
Effects of mitochondrial ATP channel modulators and calcium channel blocking on circumferential strain and longitudinal strain. DZX (diazoxide), mitoKATP channel opener; 5HD (5-hydroxydecanoate), mitoKATP channel blocker; CCB (nicardipine), calcium channel blocker; JC-1, mitochondrial membrane potential assay; H-ATP, ATP synthase activity; Ca2+, intramitochondrial Ca2+ concentration.
Figure 5
Figure 5
Effects of mitochondrial ATP channel modulators and calcium channel blockers on mitochondrial energy metabolism. DZX (diazoxide), mitoKATP channel opener; 5HD (5-hydroxydecanoate), mitoKATP channel blocker; CCB (nicardipine), calcium channel blocker; JC-1, mitochondrial membrane potential assay; H-ATP, ATP synthase activity; Ca2+, intramitochondrial Ca2+ concentration.
Figure 6
Figure 6
Abnormal mitochondrial morphology in 5-HD-administered rats. (Left, mitochondrial swelling; right, cristae disruption).
See this image and copyright information in PMC

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