{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:49:39Z","timestamp":1784072979675,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Leg muscle sympathetic nerve activity (MSNA) diminishes in healthy (HC) individuals during mild dynamic exercise but not in age\u2010matched patients with heart failure due to reduced ejection fraction (HFrEF). To elucidate the neural mechanisms responsible for such sympathetic excitation, we studied 20 stable HFrEF patients (6F; mean age 62 \u00b1 8 SD years) and 15 age\u2010matched HC (6F; mean age 59 \u00b1 7). We quantified peak oxygen uptake () and separately, fibular MSNA (microneurography) at rest and during one\u2010leg cycling (2\u00a0min each, mild (unloaded) and moderate intensity (loaded\u00a0=\u00a030\u201340% )) throughout three interventions: (1) post\u2010exercise circulatory occlusion (PECO), which isolates the leg muscle metaboreflex (MMR); (2) supine posture, which stimulates cardiopulmonary baroreceptors (CPB); and (3) 32% inspired oxygen, to supress the peripheral chemoreflex (PC). One\u2010leg cycling increased MSNA and activated the leg MMR in patients with HFrEF but not HC. MSNA at rest and during mild exercise was lower when supine than seated in both cohorts. Breathing 32% oxygen lowered the MSNA of HC but not HFrEF. In both groups, hyperoxia decreased burst frequency during low\u2010intensity cycling. Hyperoxia abolished the \u2018paradoxical\u2019 sympatho\u2010excitation of HFrEF. Thirteen participants with HFrEF were reassessed after 4 months of conventional cardiopulmonary rehabilitation. Exercise training improved  by 17% and attenuated the leg MMR response without altering CPB activation or PC suppression. We conclude that in HFrEF, all three autonomic reflexes are engaged to a varying degree by one\u2010leg cycling. Patient training attenuates the leg MMR without affecting CPB or PC modulation of MSNA during exercise.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16748-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>In HFrEF patients, an exaggerated leg MMR is the dominant sympatho\u2010excitatory reflex during one\u2010leg cycling at moderate work rates; with their MSNA response relating inversely to .<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Activation of the cardiopulmonary baroreflex and peripheral chemoreflex by exercise also contribute, suggesting that exercising supine or while breathing 32% O<jats:sub>2<\/jats:sub> may complement conventional training protocols.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>An exercise\u2010based cardiac rehabilitation programme lowers sympathetic discharge at rest and during mild intensity cycling by abolishing specifically the leg MMR response.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp287491","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T15:38:46Z","timestamp":1746977926000},"page":"3001-3017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms of sympathetic excitation during cycling exercise in heart failure with reduced ejection fraction"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7911-2950","authenticated-orcid":false,"given":"Catherine F.","family":"Notarius","sequence":"first","affiliation":[{"name":"Toronto General Hospital Research Institute University Health Network and Sinai Health Division of Cardiology  Toronto Ontario Canada"},{"name":"Faculty of Kinesiology and Physical Education University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7809-0729","authenticated-orcid":false,"given":"Mark B.","family":"Badrov","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute University Health Network and Sinai Health Division of Cardiology  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-2252","authenticated-orcid":false,"given":"Tomoyuki","family":"Tobushi","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute University Health Network and Sinai Health Division of Cardiology  Toronto Ontario 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