Abstract 18054: Improved Myocardial Function After Whole Body Periodic Acceleration (pGz) in Established mdx Cardiomyopathy
Duchenne Muscular Dystrophy (DMD) cardiomyopathy (DMD-C) is progressive leading to heart failure and death. pGz is the sinusoidal motion of the body in a head-foot direction, which activates endothelial nitric oxide synthase (eNOS) to produce small amounts of eNO in heart via pulsatile shear stress. eNO is cardioprotective and important in varied signaling pathway. We recently showed improved muscle function using pGz in a mouse model of mdx
Hypothesis: pGz may confer myocardial functional improvement in an established DMD-C.
Methods: Male MDX mice were randomized (n=12) at 7-mo of age (an age where DMD-C is already established) to receive daily pGz (ƒ=480 cpm with a displacement Gz ± 3.0 mt/sec2 ) (MDX-pGz) (1hr/day for 8 weeks or time control (MDX), a separate age matched group of wt (n=6) to serve as non-diseased controls. At 9 mo of age, invasive analysis of the pressure-volume relationship of left ventricle (LV) was carried out with a Millar catheter and a dobutamine stress test performed. In a separate group of mdx mice, pGz was performed and immunoblotting analysis done to determine expression of utrophin (UTR), sarcoglycan β (SARCβ), Dytroglycanβ(DYSβ), eNOS and p-eNOS levels in heart.
Results: Compared to wt, mdx mice had reduced LV pressure integral(LVPi) and lower dp/dt max. Treatment with pGz improved LVPi and dp/dt max. Survival to a Dobutamine stress test was: 100% wt, 80% mdx and 90% in mdx-pGz. pGz treatment preserved LVPi relationship and dp/dt max during dobutamine. pGz treatment to mdx mice increased UTR,(56% ), SARCβ (160% ),DYSβ (227%), eNOS(75%) and p-eNOS (37% ) from mdx expression levels (Figure, M±SD)
Conclusion: pGz improves myocardial functional phenotype, and preserves myocardial function after dobutamine stress in mdx mice. pGz salutatory effect is associated with an increase in eNOS, p-eNOS UTR, SARCβ, DYSβ expression. This non-invasive and non-pharmacological intervention may constitute a new therapeutic approach to treat DMD cardiomyopathy.
Author Disclosures: A. Uryash: None. J.R. Lopez: None. F.X. McGowan: None. R. Berg: None. V. Nadkarni: None. J. Adams: Ownership Interest; Modest; Stock options totaling < $10,000.
- © 2015 by American Heart Association, Inc.