Discussion
RyR2 hyperactivity, RyR2 hyperactive, VT/VF
CHRONIC HEART FAILURE, OXIDATIVE STRESS
The novel findings of this study are: (1) Inhibition of RyR2 hyperactivity with DS abolishes VT/VF and SCD by normalizing repolarization abnormalities, QTc variability, and shortening prolonged QTc in non-ischemic HF; (2) dantrolene improves β-adrenergic signaling and chronotropic competency, thereby improving LV contractility; and (3) inhibition of RyR2 with DS not only prevents the progression of HF but also reverses chronic heart failure. These findings support the idea that the coupling between chronic sympathetic activity and oxidative stress makes RyR2 hyperactive. ROS increases the channel activity by decreasing the threshold for store overload-induced CaOxidative stress has been centrally implicated in HF. We and others have shown that the ROS dynamics affect the functioning of RyR2 (