Abstract 18335: The Heart in Duchenne Muscular Dystrophy Mouse Model (mdx Mice) Loses Beta-Adrenergic Reserve at Early Age Before the Onset of Heart Failure
Duchenne muscular dystrophy (DMD) is a hereditary X-linked recessive disease that resulted from the mutation of dystrophin. Cardiac dysfunctions of this disease include heart failure and arrhythmias. The deterioration of cardiac function is manifested at the age of 6 months (6m). β-adrenergic stress test has been used to evaluate cardiac reserve in humans but so far not used for mdx patients. We studied cardiac β-adrenergic reserve to evaluate cardiac function alteration in mdx mice.
Methods: Cardiac function of mdx mice and control (CTR) mice at different ages at baseline and post isoproterenol (a β-adrenergic agonist) stress was evaluated with in vivo echocardiography (ECHO), invasive intra-LV hemodynamic and ex vivo Langendorff measurements.
Results: (1). Conventional M-mode ECHO analysis did not uncover differences in cardiac ejection fraction and fractional shortening at baseline between mdx mice and CTR mice before the age of 6m but ISO induced increases in LV ejection fraction (EF) and fractional shortening (FS) were lower in mdx mice as early as the age of 3m; (2). At baseline, speckle-tracing strain analysis had higher detection power for cardiac abnormalities and showed a subtle differences (Lateral strain of the endomyocardium: mdx 16.4% vs. control 18.4%) in myocardium contractility at baseline as early as 3m; with combination of ISO-stress and speckle-tracing strain analysis, reduced cardiac responses was very significantly at the age as young as 3m; (3). In vivo intra-LV hemodynamic measurements showed a reduction in dp/dt (21% ) and -dp/dt (30%) at the age of 8m; ISO responses was completely blunted in mdx mice at the age of 8 m and reduced in 4m mdx mice; (4). Ex vivo Langendorff studies showed that 4m mdx mouse hearts had marked decreased dp/dt and -dp/dt and after ISO, the difference was even larger (>35%). The dose-response curve shows that the mdx mouse hearts are less sensitive to ISO.
Conclusion: Although basal cardiac function looked normal in mdx mice before the age of 6m, Langendorff preparations and subtle speckle tracking ECHO analysis reveal cardiac function depression in younger mdx mice. β-adrenergic stress further brings out the difference in cardiac reserve of mdx mice as young as 3m. ZL and YL contributed to this study equally.
- Heart failure
- Beta-adrenergic receptor agonists
- Ventricular function
- Systems physiology
- © 2011 by American Heart Association, Inc.