Functional cardiac consequences of β-adrenergic stress-induced injury in the mdx mouse model of Duchenne muscular dystrophy.
Conner C EarlAreli J JavierAlyssa M RichardsLarry W MarkhamCraig J GoergenSteven S WelcPublished in: bioRxiv : the preprint server for biology (2024)
Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to enhance the cardiac phenotype in the mdx model, many methods lead to high mortality, variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo . For our study, mdx and wild-type (WT) mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathologic assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels, and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes, and diminished cardiac reserve in mdx mice compared to wild-type. Our findings highlight the utility of low-dose isoproterenol in mdx mice as a valuable model for exploring therapies targeting DMD-associated cardiac complications.
Keyphrases
- duchenne muscular dystrophy
- wild type
- left ventricular
- low dose
- muscular dystrophy
- high frequency
- stress induced
- heart failure
- magnetic resonance imaging
- high fat diet induced
- type diabetes
- risk factors
- cardiovascular events
- metabolic syndrome
- high dose
- coronary artery disease
- drug delivery
- ultrasound guided
- cancer therapy
- optical coherence tomography
- smoking cessation
- catheter ablation
- replacement therapy
- liver fibrosis