{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:27:43Z","timestamp":1789000063030,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T00:00:00Z","timestamp":1543449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001298","name":"Presbyterian Health Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001298","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AG057879"],"award-info":[{"award-number":["R21AG057879"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>What is the effect of chronic intermittent low\u2010level transcutaneous vagus nerve stimulation on cardiac inflammation, fibrosis and diastolic dysfunction in a rat model of heart failure with preserved ejection fraction?<\/jats:p>\n<\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>In salt\u2010sensitive rats fed with high salt diet, low\u2010level transcutaneous vagus nerve stimulation significantly attenuated blood pressure elevation, ameliorated diastolic function, and attenuated left ventricular inflammation and fibrosis compared to the sham group. Further studies to examine the efficacy of this novel treatment in humans are warranted.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Inflammation and fibrosis play a central role in the development of heart failure with preserved ejection fraction (HFpEF). We previously showed that low\u2010level, transcutaneous stimulation of the vagus nerve at the tragus (LLTS) is anti\u2010inflammatory. We investigated the effect of chronic intermittent LLTS on cardiac inflammation, fibrosis and diastolic dysfunction in a rat model of HFpEF. Dahl salt\u2010sensitive (DS) rats were randomized in three groups: low salt (LS, 0.3% NaCl; <jats:italic>n<\/jats:italic>\u00a0=\u00a012; control group without stimulation) and high salt (HS, 4% NaCl) with either active (<jats:italic>n<\/jats:italic>\u00a0=\u00a018) or sham (<jats:italic>n<\/jats:italic>\u00a0=\u00a018) LLTS at 7\u00a0weeks of age. After 6\u00a0weeks of diet (baseline), sham or active LLTS (20\u00a0Hz, 2\u00a0mA, 0.2\u00a0ms) was implemented for 30\u00a0min daily for 4\u00a0weeks. Echocardiography was performed at baseline and 4\u00a0weeks after treatment (endpoint). At endpoint, left ventricle (LV) histology and gene expression were examined. After 6\u00a0weeks of diets, HS rats developed hypertension and LV hypertrophy compared to LS rats. At endpoint, LLTS significantly attenuated blood pressure elevation, prevented the deterioration of diastolic function and improved LV circumferential strain, compared to the HS sham group. LV inflammatory cell infiltration and fibrosis were attenuated in the HS active compared to the HS sham group. Pro\u2010inflammatory and pro\u2010fibrotic genes (tumour necrosis factor, osteopontin, interleukin (IL)\u201011, IL\u201018 and IL\u201023A) were differentially altered in the two groups. Chronic intermittent LLTS ameliorates diastolic dysfunction, and attenuates cardiac inflammation and fibrosis in a rat model of HFpEF, suggesting that LLTS may be used clinically as a novel non\u2010invasive neuromodulation therapy in HFpEF.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep087351","type":"journal-article","created":{"date-parts":[[2018,11,6]],"date-time":"2018-11-06T11:23:44Z","timestamp":1541503424000},"page":"28-38","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Low\u2010level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction"],"prefix":"10.1113","volume":"104","author":[{"given":"Liping","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University  Wuhan 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