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Protective effects of rimeporide on left ventricular function in golden retriever muscular dystrophy dogs.

Research paper by Bijan B Ghaleh, Inès I Barthélemy, Jérôme J Wojcik, Lucien L Sambin, Alain A Bizé, Luc L Hittinger, Thien Duc TD Tran, Florence Porte FP Thomé, Stéphane S Blot, Jin Bo JB Su

Indexed on: 23 Mar '20Published on: 23 Mar '20Published in: International Journal of Cardiology



Abstract

Alterations in intracellular Na and Ca 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. 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. Copyright © 2020 Elsevier B.V. All rights reserved.

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