Yuxin Nie, Liyu Lin, Qiang Yang, Jiachang Hu, Minmin Sun, Fangfang Xiang, Xuesen Cao, Jinbo Yu, Yaqiong Wang, Jie Teng, Xiaoqiang Ding, Bo Shen, Zhen Zhang
{"title":"血液透析诱发心肌梗死大鼠模型中的线粒体功能障碍和离子失衡","authors":"Yuxin Nie, Liyu Lin, Qiang Yang, Jiachang Hu, Minmin Sun, Fangfang Xiang, Xuesen Cao, Jinbo Yu, Yaqiong Wang, Jie Teng, Xiaoqiang Ding, Bo Shen, Zhen Zhang","doi":"10.3390/biomedicines12102402","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background/Objectives</b>: 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<sup>+</sup>) and calcium (Ca<sup>2+</sup>) 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<sub>ATP</sub>) in mitigating HIMS. <b>Methods</b>: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoK<sub>ATP</sub> channel modulators were evaluated by administering diazoxide (DZX), a mitoK<sub>ATP</sub> opener, and 5-hydroxydecanoate (5-HD), a mitoK<sub>ATP</sub> blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca<sup>2+</sup> levels. Myocardial function was evaluated using speckle tracking echocardiography. <b>Results</b>: 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<sup>+</sup> and Ca<sup>2+</sup> concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. <b>Conclusions</b>: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoK<sub>ATP</sub> channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504215/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning.\",\"authors\":\"Yuxin Nie, Liyu Lin, Qiang Yang, Jiachang Hu, Minmin Sun, Fangfang Xiang, Xuesen Cao, Jinbo Yu, Yaqiong Wang, Jie Teng, Xiaoqiang Ding, Bo Shen, Zhen Zhang\",\"doi\":\"10.3390/biomedicines12102402\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background/Objectives</b>: 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<sup>+</sup>) and calcium (Ca<sup>2+</sup>) 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<sub>ATP</sub>) in mitigating HIMS. <b>Methods</b>: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoK<sub>ATP</sub> channel modulators were evaluated by administering diazoxide (DZX), a mitoK<sub>ATP</sub> opener, and 5-hydroxydecanoate (5-HD), a mitoK<sub>ATP</sub> blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca<sup>2+</sup> levels. Myocardial function was evaluated using speckle tracking echocardiography. <b>Results</b>: 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<sup>+</sup> and Ca<sup>2+</sup> concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. <b>Conclusions</b>: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoK<sub>ATP</sub> channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.</p>\",\"PeriodicalId\":8937,\"journal\":{\"name\":\"Biomedicines\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-10-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504215/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedicines\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.3390/biomedicines12102402\",\"RegionNum\":3,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedicines","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3390/biomedicines12102402","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning.
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.
BiomedicinesBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.20
自引率
8.50%
发文量
2823
审稿时长
8 weeks
期刊介绍:
Biomedicines (ISSN 2227-9059; CODEN: BIOMID) is an international, scientific, open access journal on biomedicines published quarterly online by MDPI.