Max J Hilz1,2, Sankanika Roy3, Carmen de Rojas Leal4, Mao Liu5, Francesca Canavese6, Klemens Winder6, Katharina M Hoesl7, De-Hyung Lee8, Ralf A Linker8, Ruihao Wang6. 1. Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054, Erlangen, Germany. max.hilz@outlook.com. 2. Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. max.hilz@outlook.com. 3. Department of Internal Medicine, Nottingham University Hospitals, Nottingham, UK. 4. Department of Neurology, Hospital Universitario Virgen de la Victoria, University of Malaga, Malaga, Spain. 5. Department of Neurology, Tongji Hospital, Tongji Medical College, HUST, Wuhan, People's Republic of China. 6. Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054, Erlangen, Germany. 7. Department of Psychiatry and Psychotherapy, Paracelsus Medical University, Nuremberg, Germany. 8. Department of Neurology, University Hospital Regensburg, University of Regensburg, Regensburg, Germany.
Abstract
BACKGROUND AND PURPOSE: Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation. PATIENTS AND METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6 hours 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: p < 0.05). RESULTS: RRIs at VM phase 1, VM phase 2 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4 hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6 hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5 hours, and significantly higher after 4 hours than before fingolimod initiation. CONCLUSIONS: VR-decreases 3-6 hours 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.
BACKGROUND AND PURPOSE: Initial cardiovascular fingolimod effects might compromise baroreflex responses to rapid blood pressure (BP) changes during common Valsalva-like maneuvers. This study evaluated cardiovascular responses to Valsalva maneuver (VM)-induced baroreceptor unloading and loading upon fingolimod initiation. PATIENTS AND METHODS: Twenty-one patients with relapsing-remitting multiple sclerosis performed VMs before and 0.5, 1, 2, 3, 4, 5, and 6 hours 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: p < 0.05). RESULTS: RRIs at VM phase 1, VM phase 2 early, and VM phase 2 late were higher after than before fingolimod initiation, and maximal after 4 hours. Fingolimod did not affect the longest RRIs upon strain release, but after 3, 5, and 6 hours lowered the highest BPsys values during overshoot and all BPdia values, and thus reduced VRs. BRG was slightly higher after 3 and 5 hours, and significantly higher after 4 hours than before fingolimod initiation. CONCLUSIONS: VR-decreases 3-6 hours 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.
Authors: Magdalena Krbot Skorić; Luka Crnošija; Tereza Gabelić; Barbara Barun; Ivan Adamec; Anamari Junaković; Tin Pavičić; Berislav Ruška; Mario Habek Journal: Mult Scler Relat Disord Date: 2019-01-03 Impact factor: 4.339
Authors: Oliver Findling; Larissa Hauer; Thomas Pezawas; Paulus S Rommer; Walter Struhal; Johann Sellner Journal: J Clin Med Date: 2020-01-24 Impact factor: 4.241