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This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6\u00a0hours after fingolimod initiation. We recorded heart rate (HR) as RR intervals (RRI), systolic and diastolic BP (BPsys, BPdia) during VM phase 1, VM phase 2 early, VM phase 2 late, and VM phase 4. Using linear regression analysis between decreasing BPsys and RRI values during VM phase 2 early, we determined baroreflex gain (BRG) reflecting vagal withdrawal and sympathetic activation upon baroreceptor unloading. To assess cardiovagal activation upon baroreceptor loading, we calculated Valsalva ratios (VR) between maximal and minimal RRIs after strain release. Analysis of variance or Friedman tests with post hoc analysis compared corresponding parameters at the eight time points (significance:<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RRIs at VM phase 1, VM phase\u00a02 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4\u00a0hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6\u00a0hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5\u00a0hours, and significantly higher after 4\u00a0hours than before fingolimod initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>VR-decreases 3\u20136\u00a0hours after fingolimod initiation are physiologic results of fingolimod-associated attenuations of BP and HR increases at the end of strain and do not suggest impaired cardiovagal activation upon baroreceptor loading. Stable and at the time of HR nadir significantly increased BRGs indicate improved responses to baroreceptor unloading. Thus, cardiovascular fingolimod effects do not impair autonomic responses to sudden baroreceptor loading or unloading but seem to be mitigated by baroreflex resetting.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10072-020-05004-1","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:03:17Z","timestamp":1610622197000},"page":"111-121","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cardiovascular fingolimod effects on rapid baroreceptor unloading are counterbalanced by baroreflex resetting"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6802-1751","authenticated-orcid":false,"given":"Max J.","family":"Hilz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sankanika","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"de Rojas Leal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Canavese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klemens","family":"Winder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina M.","family":"Hoesl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf A.","family":"Linker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruihao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"issue":"10005","key":"5004_CR1","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1016\/S0140-6736(15)61485-4","volume":"386","author":"A Appelboam","year":"2015","unstructured":"Appelboam A, Reuben A, Mann C, Gagg J, Ewings P, Barton A, Lobban T, Dayer M, Vickery J, Benger J, R. t. collaborators (2015) Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. 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Roy, de Rojas Leal, Liu, Canavese, Winder, Hoesl, and Wang had no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Ethics Committee of the University of Erlangen-Nuremberg and registered at the German Clinical Trial Register (DRKS00004548).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"After a detailed explanation of the study and all its procedures, all study participants gave their written informed consent according to the declaration of Helsinki.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}