Sijin Wu MD , Zhongli Chen MD , Yuan Gao MD , Mengxing Cai MD , Jiandu Yang MD , Jing Han PhD , Ruohan Chen MD , Ying Wu MD, PhD , Yan Dai MD, PhD, FHRS , Keping Chen MD, PhD, FHRS
{"title":"血清素和血清素能相关代谢物在血管迷走性晕厥发病机制中的作用。","authors":"Sijin Wu MD , Zhongli Chen MD , Yuan Gao MD , Mengxing Cai MD , Jiandu Yang MD , Jing Han PhD , Ruohan Chen MD , Ying Wu MD, PhD , Yan Dai MD, PhD, FHRS , Keping Chen MD, PhD, FHRS","doi":"10.1016/j.hrthm.2024.09.047","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.</div></div><div><h3>Objective</h3><div>This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.</div></div><div><h3>Methods</h3><div>Sixty-six patients [mean age 45.6±17.0 years; 33 women (50%)] with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels and plasma concentrations of serotonergic-related metabolites—including serotonin’s precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid, and synthesis source tryptophan—were measured using the liquid chromatography tandem mass spectrometry method.</div></div><div><h3>Results</h3><div>HUTT was positive in 45 (68.2%) patients and negative in 21 (21.8%) patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (<em>P</em><.001 and <em>P</em>=.040, respectively) as well as before and after syncope (<em>P</em><.001 for all), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (<em>P</em>=.037), and a greater change in serotonin correlated with a shorter time to syncope (<em>R</em><sup>2</sup>=0.38; <em>P</em>=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.</div></div><div><h3>Conclusion</h3><div>Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.</div></div>","PeriodicalId":12886,"journal":{"name":"Heart rhythm","volume":"22 7","pages":"Pages 1810-1817"},"PeriodicalIF":5.7000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of serotonin and serotonergic-related metabolites in the pathogenesis of vasovagal syncope\",\"authors\":\"Sijin Wu MD , Zhongli Chen MD , Yuan Gao MD , Mengxing Cai MD , Jiandu Yang MD , Jing Han PhD , Ruohan Chen MD , Ying Wu MD, PhD , Yan Dai MD, PhD, FHRS , Keping Chen MD, PhD, FHRS\",\"doi\":\"10.1016/j.hrthm.2024.09.047\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.</div></div><div><h3>Objective</h3><div>This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.</div></div><div><h3>Methods</h3><div>Sixty-six patients [mean age 45.6±17.0 years; 33 women (50%)] with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels and plasma concentrations of serotonergic-related metabolites—including serotonin’s precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid, and synthesis source tryptophan—were measured using the liquid chromatography tandem mass spectrometry method.</div></div><div><h3>Results</h3><div>HUTT was positive in 45 (68.2%) patients and negative in 21 (21.8%) patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (<em>P</em><.001 and <em>P</em>=.040, respectively) as well as before and after syncope (<em>P</em><.001 for all), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (<em>P</em>=.037), and a greater change in serotonin correlated with a shorter time to syncope (<em>R</em><sup>2</sup>=0.38; <em>P</em>=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.</div></div><div><h3>Conclusion</h3><div>Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.</div></div>\",\"PeriodicalId\":12886,\"journal\":{\"name\":\"Heart rhythm\",\"volume\":\"22 7\",\"pages\":\"Pages 1810-1817\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Heart rhythm\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1547527124033757\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/21 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Heart rhythm","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1547527124033757","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/21 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Role of serotonin and serotonergic-related metabolites in the pathogenesis of vasovagal syncope
Background
Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.
Objective
This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.
Methods
Sixty-six patients [mean age 45.6±17.0 years; 33 women (50%)] with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels and plasma concentrations of serotonergic-related metabolites—including serotonin’s precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid, and synthesis source tryptophan—were measured using the liquid chromatography tandem mass spectrometry method.
Results
HUTT was positive in 45 (68.2%) patients and negative in 21 (21.8%) patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (P<.001 and P=.040, respectively) as well as before and after syncope (P<.001 for all), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (P=.037), and a greater change in serotonin correlated with a shorter time to syncope (R2=0.38; P=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.
Conclusion
Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.
期刊介绍：
HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability.
HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community.
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.
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