Increased sympathetic outflow induced by ventromedial hypothalamic nucleus activation aggravates cardiac electrophysiology disturbance after myocardial ischemia–reperfusion injury

IF 3.2 2区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

International journal of cardiology Pub Date : 2025-07-16 DOI:10.1016/j.ijcard.2025.133634

Xiao Xu , Zihan Liu , Zhihao Liu , Zeyan Li , Yuyang Zhou , Huixin Zhou , Wuping Tan , Chen Peng , Siyi Cheng , Yueyi Wang , Liping Zhou , Xiaoya Zhou , Hong Jiang

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Abstract

Background and aims

The ventromedial hypothalamus (VMH) is the key brain region related to emotional stress and sympathetic activity, which can exacerbate myocardial ischemia–reperfusion (I/R) injury and induce severe ventricular arrhythmia (VA). We aim to investigate the role of increased sympathetic outflow induced by VMH activation after myocardial I/R injury, especially the changes of cardiac electrical activity.

Methods

Sprague-Dawley rats were divided randomly into the Sham, I/R, hM3d(Gq) and hM4d(Gi) groups, with VMH specifically activated or inhibited using Designer Receptors Exclusively Activated Designer Drugs (DREADDs) technology. I/R model was inducted by ligation of the left coronary artery for 45 min. After 24 h of reperfusion, electrocardiogram and cardiac electrophysiological studies were conducted. Then the samples were collected for histopathological and molecular analyses.

Results

VMH was chemogenetically manipulated using DREADDs. The activation of VMH significantly increased systemic and local cardiac sympathetic activity, aggravating I/R injury, which reduced following VMH inhibition. The ventricular electrophysiology disturbance exacerbated following VMH activation and ameliorated following VMH inhibition. The expression of myocardial potassium channel including the rapid delayed rectifier potassium channel (Kcnd3), the inward rectifier potassium channel (Kcnj2) and the slow delayed rectifier potassium channel (Kcnq1) was markedly suppressed following VMH activation, which may represent a key mechanism underlying repolarization abnormalities and increased VA susceptibility.

Conclusions

VMH activation exacerbated cardiac electrophysiology disturbance and increased the susceptibility of VA after I/R injury via increased sympathetic outflow, a process closely linked to repolarization impairment caused by potassium channel dysfunction.

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下丘脑腹内侧核激活引起的交感神经流出增加加重了心肌缺血再灌注损伤后的心脏电生理障碍

背景与目的下丘脑腹内侧（VMH）是与情绪应激和交感神经活动相关的关键脑区，可加重心肌缺血再灌注（I/R）损伤，诱发严重室性心律失常（VA）。我们旨在探讨VMH激活对I/R心肌损伤后交感神经流出增加的作用，特别是对心电活动的影响。方法将sd - dawley大鼠随机分为Sham组、I/R组、hM3d（Gq）组和hM4d（Gi）组，采用设计物受体特异性激活设计物药物（DREADDs）技术特异性激活或抑制VMH。结扎左冠状动脉45 min，建立I/R模型，再灌注24 h后进行心电图和心脏电生理观察。然后收集样本进行组织病理学和分子分析。结果利用reads对vmh进行化学修饰。VMH的激活显著增加全身和局部心脏交感神经活动，加重I/R损伤，VMH抑制后I/R损伤减轻。心室电生理障碍在VMH激活后加重，在VMH抑制后改善。心肌钾通道包括快速延迟整流钾通道（Kcnd3）、向内整流钾通道（Kcnj2）和慢延迟整流钾通道（Kcnq1）的表达在VMH激活后被明显抑制，这可能是复极化异常和VA易感性增加的关键机制。结论svmh激活可加重I/R损伤后的心脏电生理障碍，通过增加交感神经流出增加VA的易感性，这一过程与钾通道功能障碍引起的复极化损伤密切相关。

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来源期刊

International journal of cardiology 医学-心血管系统

CiteScore

6.80

自引率

5.70%

发文量

758

审稿时长

44 days

期刊介绍： The International Journal of Cardiology is devoted to cardiology in the broadest sense. Both basic research and clinical papers can be submitted. The journal serves the interest of both practicing clinicians and researchers. In addition to original papers, we are launching a range of new manuscript types, including Consensus and Position Papers, Systematic Reviews, Meta-analyses, and Short communications. Case reports are no longer acceptable. Controversial techniques, issues on health policy and social medicine are discussed and serve as useful tools for encouraging debate.