Aim: 

To gain mechanistic insight into DMD cardiomyopathy, we compared a number of cardiac electrophysiological, structural and molecular features in: (i) MDX mice treated with histone deacetylase inhibitor suberoylanilide hydroxamic acid (5 mg/kg, for 90 days) (SAHA), and (ii) untreated (MDX) and wild type (WT) mice.

Methods: 

In 5-month old WT (n = 14), MDX (n = 16) and SAHA (n = 15) mice we determined: (i) propensity to stress induced (restraint test) ventricular arrhythmias (VAs) and heart-rate-based indices of cardiac autonomic control (SDRR and r-MSSD) by telemetry ECG, (ii) post-transcriptional expression of Cx 43, 40, 32, and Nav 1.5 Sodium channel, (iii) intercellular Cx organization by confocal microscopy.

Results: 

VAs were negligible at rest in all animals. Numerous VAs occurred during restraint in untreated MDX mice and were reduced by SAHA treatment to WT values (p < 0.01). Heart rate, SDRR and r-MSSD did not show any differences among groups at rest and during restraint. Cx 32 and Cx 40 were respectively up-and down-regulated by SAHA which also counteracted a reduced Nav 1.5 expression occurring in MDX mice. Cx 43 values were similar in all groups.

Conclusions: 

Decreased inducible VAs and increased Nav 1.5 expression in SAHA treated mice suggest an involvement of Na-channel in DMD arrhythmogenesis. SAHA-induced remodeling of Cx 32 and Cx 40 may indicate a contribution of these molecules to ventricular electrical instability in DMD cardiomyopathy.