Protective effects of rimeporide on left ventricular function in golden retriever muscular dystrophy dogs
| Autor: | Bijan Ghaleh, Inès Barthélémy, Luc Hittinger, Jérôme Wojcik, Stéphane Blot, Alain Bizé, Thien Duc Tran, Jin Bo Su, Lucien Sambin, Florence Porte Thomé |
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| Přispěvatelé: | Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) |
| Rok vydání: | 2019 |
| Předmět: |
Golden retriever muscular dystrophy
medicine.medical_specialty Duchenne muscular dystrophy [SDV]Life Sciences [q-bio] 030204 cardiovascular system & hematology Placebo Ventricular Function Left 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Dogs Internal medicine medicine Animals Humans 030212 general & internal medicine Cause of death Ejection fraction Ventricular function business.industry Heart medicine.disease 3. Good health Muscular Dystrophy Duchenne Disease Models Animal chemistry Echocardiography Heart failure Rimeporide Cardiology Cardiology and Cardiovascular Medicine business Anti-Arrhythmia Agents |
| Zdroj: | International Journal of Cardiology International Journal of Cardiology, Elsevier, 2020, 312, pp.89-95. ⟨10.1016/j.ijcard.2020.03.031⟩ |
| ISSN: | 1874-1754 0167-5273 |
| Popis: | Background Alterations in intracellular Na+ and Ca2+ have been observed in patients with Duchenne muscular dystrophy (DMD) and in animal models of DMD, and inhibition of Na+-H+ exchanger 1 (NHE1) by rimeporide has previously demonstrated cardioprotective effects in animal models of myocardial ischemia and heart failure. Since heart failure is becoming a predominant cause of death in DMD patients, this study aimed to demonstrate a cardioprotective effect of chronic administration of rimeporide in a canine model of DMD. 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. |
| Databáze: | OpenAIRE |
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