Vagus Nerve Stimulation by Focused Ultrasound Attenuates Acute Myocardial Ischemia/Reperfusion Injury Predominantly Through Cholinergic Anti-inflammatory Pathway.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2025-06-02 DOI:10.1007/s10557-025-07718-w

Qian Zhang, Qianyun Cai, Shenrong Zhong, Qin Li, Weibao Qiu, Juefei Wu

{"title":"Vagus Nerve Stimulation by Focused Ultrasound Attenuates Acute Myocardial Ischemia/Reperfusion Injury Predominantly Through Cholinergic Anti-inflammatory Pathway.","authors":"Qian Zhang, Qianyun Cai, Shenrong Zhong, Qin Li, Weibao Qiu, Juefei Wu","doi":"10.1007/s10557-025-07718-w","DOIUrl":null,"url":null,"abstract":"Purpose: This study investigates the cardioprotective effects of focused ultrasound stimulation (FUS) as a novel, noninvasive intervention for mitigating acute myocardial ischemia/reperfusion (I/R) injury.Methods: In rat I/R models (30-min left anterior descending coronary artery (LAD) occlusion followed by 2-/24-h reperfusion), FUS was applied to the right cervical vagus nerve during early reperfusion (10-60 min post-reperfusion). The effects of FUS were assessed by analyzing inflammatory markers, arrhythmia incidence, pathological changes, echocardiographic parameters, pro-/anti-oxidative biomarkers, myocardial fibrosis, and infarct size. To elucidate the underlying mechanism, vagotomy and atropine administration were performed.Results: FUS significantly reduced heart rate and inflammation in the 2-h reperfusion model. Compared to the I/R group, the I/R + FUS group exhibited markedly decreased premature ventricular contractions (221.00 ± 166.93 vs 83.11 ± 34.08, p < 0.05), ventricular tachycardia and ventricular fibrillation (16.67 ± 10.68 vs. 3.67 ± 3.24, p < 0.01), and arrhythmia scores during reperfusion (2.44 ± 1.13 vs. 0.67 ± 0.50, p < 0.01). In the 24-h reperfusion model, FUS significantly reduced myocardial fibrosis and infarct size (infarct size/area at risk 49.60 ± 9.17% vs. 20.73 ± 4.91%, p < 0.001) and preserved left ventricular ejection fraction (35.68 ± 9.95% vs 56.73 ± 2.64%, p < 0.001). The protective effects of FUS were abolished by vagotomy or atropine, suggesting the cholinergic anti-inflammatory pathway as a potential mechanism.Conclusion: Targeted FUS neuromodulation exerts acute and sustained cardioprotection against I/R injury primarily through cholinergic anti-inflammatory mechanisms, offering a safer and more accessible alternative to traditional treatments.","PeriodicalId":9557,"journal":{"name":"Cardiovascular Drugs and Therapy","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Drugs and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10557-025-07718-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Purpose: This study investigates the cardioprotective effects of focused ultrasound stimulation (FUS) as a novel, noninvasive intervention for mitigating acute myocardial ischemia/reperfusion (I/R) injury.

Methods: In rat I/R models (30-min left anterior descending coronary artery (LAD) occlusion followed by 2-/24-h reperfusion), FUS was applied to the right cervical vagus nerve during early reperfusion (10-60 min post-reperfusion). The effects of FUS were assessed by analyzing inflammatory markers, arrhythmia incidence, pathological changes, echocardiographic parameters, pro-/anti-oxidative biomarkers, myocardial fibrosis, and infarct size. To elucidate the underlying mechanism, vagotomy and atropine administration were performed.

Results: FUS significantly reduced heart rate and inflammation in the 2-h reperfusion model. Compared to the I/R group, the I/R + FUS group exhibited markedly decreased premature ventricular contractions (221.00 ± 166.93 vs 83.11 ± 34.08, p < 0.05), ventricular tachycardia and ventricular fibrillation (16.67 ± 10.68 vs. 3.67 ± 3.24, p < 0.01), and arrhythmia scores during reperfusion (2.44 ± 1.13 vs. 0.67 ± 0.50, p < 0.01). In the 24-h reperfusion model, FUS significantly reduced myocardial fibrosis and infarct size (infarct size/area at risk 49.60 ± 9.17% vs. 20.73 ± 4.91%, p < 0.001) and preserved left ventricular ejection fraction (35.68 ± 9.95% vs 56.73 ± 2.64%, p < 0.001). The protective effects of FUS were abolished by vagotomy or atropine, suggesting the cholinergic anti-inflammatory pathway as a potential mechanism.

Conclusion: Targeted FUS neuromodulation exerts acute and sustained cardioprotection against I/R injury primarily through cholinergic anti-inflammatory mechanisms, offering a safer and more accessible alternative to traditional treatments.

查看原文本刊更多论文

聚焦超声刺激迷走神经主要通过胆碱能抗炎途径减轻急性心肌缺血/再灌注损伤。

目的：本研究探讨聚焦超声刺激（FUS）作为一种新型的、无创的缓解急性心肌缺血/再灌注（I/R）损伤的心脏保护作用。方法：大鼠I/R模型（左冠状动脉前降支闭塞30分钟，再灌注2-/24小时），在再灌注早期（再灌注后10-60分钟）将FUS应用于右侧颈迷走神经。通过分析炎症标志物、心律失常发生率、病理改变、超声心动图参数、促/抗氧化生物标志物、心肌纤维化和梗死面积来评估FUS的作用。为了阐明其潜在的机制，迷走神经切开术和阿托品给药。结果：在2 h再灌注模型中，FUS显著降低心率和炎症反应。与I/R组相比，I/R + FUS组室性早搏（221.00±166.93 vs 83.11±34.08,p < 0.05）、室性心动过速和心室颤动（16.67±10.68 vs 3.67±3.24,p < 0.01）、再灌注时心律失常评分（2.44±1.13 vs 0.67±0.50,p < 0.01）明显降低。在24小时再灌注模型中，FUS显著降低心肌纤维化和梗死面积（梗死面积/危险面积49.60±9.17%比20.73±4.91%,p < 0.001），并保持左心室射血分数（35.68±9.95%比56.73±2.64%,p < 0.001）。迷走神经切断或阿托品可消除FUS的保护作用，提示胆碱能抗炎途径可能是其潜在机制。结论：靶向FUS神经调节主要通过胆碱能抗炎机制对I/R损伤发挥急性和持续的心脏保护作用，为传统治疗提供了一种更安全、更容易获得的替代方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.