Acute Fingolimod Effects on Baroreflex and Cardiovascular Autonomic Control in Multiple Sclerosis.
autonomic system
baroreflex sensitivity
fingolimod
multiple sclerosis
Journal
Journal of central nervous system disease
ISSN: 1179-5735
Titre abrégé: J Cent Nerv Syst Dis
Pays: United States
ID NLM: 101595026
Informations de publication
Date de publication:
2019
2019
Historique:
received:
23
08
2018
accepted:
20
04
2019
entrez:
18
6
2019
pubmed:
18
6
2019
medline:
18
6
2019
Statut:
epublish
Résumé
Fingolimod, an oral drug used in multiple sclerosis (MS) treatment, exerts its action through S1P-receptor engagement. These receptors are also expressed in heart and endothelial cells. The engagement of receptors on the atrial heart myocytes may cause a slowing effect on heart rate (HR). We aimed to explore the acute effect of fingolimod on the cardiac autonomic control, a side-effect of the drug that still needs to be clarified. In 10 MS patients, we investigated the influence of the first administration of fingolimod (0.5 mg) on sympathetic and parasympathetic indexes via the analysis of the HR variability, and on the baroreflex sensitivity via sequence and alpha coefficient techniques. Fingolimod produced an average HR maximal drop of 12.7 (7.8) beats/min and the minimal HR occurred after 2.73 (0.38) hours from the dose administration. The pulse interval (PI) mean value and the pNN50 and RMSSD indexes of parasympathetic drive to the heart significantly increased. Interestingly, in 6 out of 10 patients also the power in the low-frequency band (LF) increased. The baroreflex sensitivity was not modified by the first dose of the drug. Our findings indicate that although the first dose of fingolimod invariably activates the parasympathetic system, in several subjects, it may induce also a surge in the sympathetic cardiac drive. This suggests that not only the vagal, as usually assumed, but also the sympathetic autonomic branch should be considered in the risk profile assessment of MS patients starting treatment with fingolimod.
Sections du résumé
BACKGROUND
BACKGROUND
Fingolimod, an oral drug used in multiple sclerosis (MS) treatment, exerts its action through S1P-receptor engagement. These receptors are also expressed in heart and endothelial cells. The engagement of receptors on the atrial heart myocytes may cause a slowing effect on heart rate (HR). We aimed to explore the acute effect of fingolimod on the cardiac autonomic control, a side-effect of the drug that still needs to be clarified.
METHODS
METHODS
In 10 MS patients, we investigated the influence of the first administration of fingolimod (0.5 mg) on sympathetic and parasympathetic indexes via the analysis of the HR variability, and on the baroreflex sensitivity via sequence and alpha coefficient techniques.
RESULTS
RESULTS
Fingolimod produced an average HR maximal drop of 12.7 (7.8) beats/min and the minimal HR occurred after 2.73 (0.38) hours from the dose administration. The pulse interval (PI) mean value and the pNN50 and RMSSD indexes of parasympathetic drive to the heart significantly increased. Interestingly, in 6 out of 10 patients also the power in the low-frequency band (LF) increased. The baroreflex sensitivity was not modified by the first dose of the drug.
CONCLUSIONS
CONCLUSIONS
Our findings indicate that although the first dose of fingolimod invariably activates the parasympathetic system, in several subjects, it may induce also a surge in the sympathetic cardiac drive. This suggests that not only the vagal, as usually assumed, but also the sympathetic autonomic branch should be considered in the risk profile assessment of MS patients starting treatment with fingolimod.
Identifiants
pubmed: 31205439
doi: 10.1177/1179573519849945
pii: 10.1177_1179573519849945
pmc: PMC6537493
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1179573519849945Déclaration de conflit d'intérêts
Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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