Protective effects of rimeporide on left ventricular function in golden retriever muscular dystrophy dogs.
Canine model of Duchenne muscular dystrophy
Echocardiography
Left ventricular function
Na(+)-H(+) exchanger isoform 1
Rimeporide
Journal
International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
19
11
2019
revised:
24
02
2020
accepted:
11
03
2020
pubmed:
23
3
2020
medline:
15
5
2021
entrez:
23
3
2020
Statut:
ppublish
Résumé
Alterations in intracellular Na Golden retriever muscular dystrophy (GRMD) dogs were randomized to orally receive rimeporide (10 mg/kg, twice a day) or placebo from 2 months to 1 year of age. Left ventricular (LV) function was assessed by conventional and advanced echocardiography. Compared with placebo-treated GRMD, LV function deterioration with age was limited in rimeporide-treated GRMD dogs as indicated by the preservation of LV ejection fraction as well as overall cardiac parameters different from placebo-treated dogs, as revealed by composite cardiac scores and principal component analysis. In addition, principal component analysis clustered rimeporide-treated GRMD dogs close to healthy control dogs. Chronic administration of the NHE1 inhibitor rimeporide exerted a protective effect against LV function decline in GRMD dogs. This study provides proof of concept to explore the cardiac effects of rimeporide in DMD patients.
Sections du résumé
BACKGROUND
Alterations in intracellular Na
METHODS
Golden retriever muscular dystrophy (GRMD) dogs were randomized to orally receive rimeporide (10 mg/kg, twice a day) or placebo from 2 months to 1 year of age. Left ventricular (LV) function was assessed by conventional and advanced echocardiography.
RESULTS
Compared with placebo-treated GRMD, LV function deterioration with age was limited in rimeporide-treated GRMD dogs as indicated by the preservation of LV ejection fraction as well as overall cardiac parameters different from placebo-treated dogs, as revealed by composite cardiac scores and principal component analysis. In addition, principal component analysis clustered rimeporide-treated GRMD dogs close to healthy control dogs.
CONCLUSIONS
Chronic administration of the NHE1 inhibitor rimeporide exerted a protective effect against LV function decline in GRMD dogs. This study provides proof of concept to explore the cardiac effects of rimeporide in DMD patients.
Identifiants
pubmed: 32199683
pii: S0167-5273(19)35776-6
doi: 10.1016/j.ijcard.2020.03.031
pii:
doi:
Substances chimiques
Anti-Arrhythmia Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-95Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest F. Porte Thomé and T. D. Tran are employees of the EspeRare, a not-for-profit foundation. F. Porte Thomé is a co-founder of the EspeRare foundation. Employees and founders of the EspeRare Foundation do not own stock or options. The patent on rimeporide has expired and these results will not lead to patent prosecution. The other authors have nothing to declare.