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.

中文翻译：

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气压芬戈莫德对快速压力感受器卸载的作用通过压力感受器复位来抵消

背景和目的

最初的心血管芬戈莫德效应可能会破坏普通Valsalva样动作中对快速血压（BP）变化的压力反射反应。这项研究评估了芬戈莫德启动后对Valsalva动作（VM）诱导的压力感受器卸载和加载的心血管反应。

患者和方法

21名复发缓解型多发性硬化症患者在芬戈莫德开始治疗之前和之后0.5、1、2、3、4、5和6小时进行了VM。我们将心率（HR）记录为RR间隔（RRI），VM阶段1，VM阶段2早期，VM阶段2晚期和VM阶段4期间的收缩压和舒张压BP（BPsys，BPdia）。在降低的BPsys之间进行线性回归分析VM阶段2早期的RRI和RRI值，我们确定了压力感受器增益（BRG），反映了压力感受器卸载后迷走神经退缩和交感神经激活。为了评估压力感受器负荷后的心动过速，我们计算了释放菌株后最大和最小RRI之间的瓦尔瓦尔比（VR）。方差分析或事后分析的Friedman检验比较了八个时间点的相应参数（重要性：p <0.05）。

结果

VM阶段1，VM阶段2早期和VM阶段2晚期的RRI在芬戈莫德启动后高于在芬戈莫德启动前，在4小时后达到最大值。芬戈莫德在释放菌株时不会影响最长的RRI，但是在过冲，所有BPdia值后的3、5和6小时后，最高BPsys值降低，从而降低了VR。在3和5小时后，BRG略高于芬戈莫德起始前，并且在4小时后显着更高。

结论

芬戈莫德启动后3-6小时VR降低是芬戈莫德在应变结束时相关的BP和HR衰减的生理结果，并且并不表明在压力感受器负荷后心律失常激活受到损害。稳定并且在HR最低点时，BRG显着增加，表明对压力感受器卸载的反应有所改善。因此，心血管的芬戈莫德效应不会削弱对突然压力感受器加载或卸载的自主反应，但似乎可以通过压力感受器复位来减轻。