Ivabradine acutely improves cardiac Ca handling and function in a rat model of Duchenne muscular dystrophy. Issue 7 (9th April 2023)

• Record Type: Journal Article
• Authors: Szabo, Petra Lujza; Marksteiner, Jessica; Ebner, Janine; Dostal, Christopher; Podesser, Bruno K.; Sauer, Jakob; Kubista, Helmut; Todt, Hannes; Hackl, Benjamin; Koenig, Xaver; Kiss, Attila; Hilber, Karlheinz
• Is Part Of: Physiological reports. Volume 11:Issue 7(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-04-09
• Subjects: Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.15664
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: The muscular dystrophies caused by dystrophin deficiency, the so‐called dystrophinopathies, are associated with impaired cardiac contractility and arrhythmias, which considerably contribute to disease morbidity and mortality. Impaired Ca handling in ventricular cardiomyocytes has been identified as a causative factor for complications in the dystrophic heart, and restoration of normal Ca handling in myocytes has emerged as a promising new therapeutic strategy. In the present study, we explored the hypothesis that ivabradine, a drug clinically approved for the treatment of heart failure and stable angina pectoris, improves Ca handling in dystrophic cardiomyocytes and thereby enhances contractile performance in the dystrophic heart. Therefore, ventricular cardiomyocytes were isolated from the hearts of adult dystrophin‐deficient DMD mdx rats, and the effects of acutely applied ivabradine on intracellular Ca transients were tested. In addition, the drug's acute impact on cardiac function in DMD mdx rats was assessed by transthoracic echocardiography. We found that administration of ivabradine to DMD mdx rats significantly improved cardiac function. Moreover, the amplitude of electrically induced intracellular Ca transients in ventricular cardiomyocytes isolated from DMD mdx rats was increased by the drug. We conclude that ivabradine enhances Ca release from the sarcoplasmic reticulum in dystrophic cardiomyocytes and thereby improves contractile performance in the dystrophic heart. Abstract : We have investigated the acute effects of the heart rate‐ lowering drug ivabradine on cardiac Ca handling and function in a rat model of Duchenne muscular dystrophy. Our findings suggest that the drug improves Ca handling in dystrophic cardiomyocytes and thereby enhances contractile performance in the dystrophic heart.