Hilz Max J, Roy Sankanika, de Rojas Leal Carmen, Liu Mao, Canavese Francesca, Winder Klemens, Hoesl Katharina M, Lee De-Hyung, Linker Ralf A, Wang Ruihao
Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, D-91054, Erlangen, Germany.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neurol Sci. 2021 Jan;42(1):111-121. doi: 10.1007/s10072-020-05004-1. Epub 2021 Jan 14.
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.
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).
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.
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.
在常见的类似瓦尔萨尔瓦动作过程中，初始心血管方面的芬戈莫德效应可能会损害压力反射对快速血压（BP）变化的反应。本研究评估了在开始使用芬戈莫德时，对瓦尔萨尔瓦动作（VM）诱发的压力感受器卸载和加载的心血管反应。
21例复发缓解型多发性硬化患者在开始使用芬戈莫德前以及开始后0.5、1、2、3、4、5和6小时进行VM动作。我们记录了VM第1阶段、VM第2阶段早期、VM第2阶段晚期和VM第4阶段期间的心率（HR）作为RR间期（RRI）、收缩压和舒张压（BPsys、BPdia）。通过在VM第2阶段早期BPsys降低值与RRI值之间进行线性回归分析，我们确定了反映压力感受器卸载时迷走神经撤离和交感神经激活的压力反射增益（BRG）。为了评估压力感受器加载时的心脏迷走神经激活情况，我们计算了应变释放后最大和最小RRIs之间的瓦尔萨尔瓦比值（VR）。方差分析或弗里德曼检验以及事后分析比较了八个时间点的相应参数（显著性：p < 0.05）。
在VM第1阶段、VM第2阶段早期和VM第2阶段晚期，RRI在开始使用芬戈莫德后高于使用前，且在4小时后达到最高。芬戈莫德不影响应变释放时最长的RRIs，但在3、5和6小时后降低了过冲期间的最高BPsys值以及所有BPdia值，从而降低了VRs。BRG在3和5小时后略有升高，在4小时后显著高于开始使用芬戈莫德前。
开始使用芬戈莫德后3 - 6小时VR降低是芬戈莫德相关的应变末期BP和HR升高减弱的生理结果，并不表明压力感受器加载时心脏迷走神经激活受损。稳定且在HR最低点时显著升高的BRGs表明对压力感受器卸载的反应得到改善。因此，心血管方面的芬戈莫德效应不会损害对突然的压力感受器加载或卸载的自主反应，而是似乎通过压力反射重置得到缓解。
