Graphical abstract.
arrhythmogenesis, HF decrease, VT/VF, Pressure overload-induced structural alterations, fibrosis, cardiac decompensation
HEART DISEASE, CONTRACTION, FIBROSIS, PVC, CARDIAC DECOMPENSATION
Stress-induced reactive oxygen species (ROS) increases CaIn normal physiology, transient stimulation of the β-adrenergic receptors prompts a positive inotropic response to meet the physiological demands. This includes the opening of L-type calcium channels (LTCCs) and the release of cytosolic calcium from the SR, triggering contraction through the activation of ryanodine receptors. Tight regulation of CaIn the GP model of non-ischemic HF and SCD, we found that not only SERCA and RyR2 protein expression was downregulated, but the proteins were also hyperphosphorylated. Treatment with an mROS scavenger prevented these alterations from occurring (Our results show that chronic treatment with dantrolene in HF/SCD animal prevents lethal VT/VF, prevents HF, and delays the onset of cardiac decompensation in pressure overload. The effects of dantrolene on RyR2 was reflected by a decrease in oxidation of the RyR2 at the molecular level, a decrease in PVC burden, and an improvement in survival at the functional level in vivo. Pressure overload-induced structural alterations like increased fibrosis (Comprehensive analysis of the electrophysiological properties of the HF/SCD group shows that with chronic HF decrease in heart rate variability, QT prolongation, and increase in dispersion of repolarization. An increase in QT variability is due to the reduction of repolarization lability. Reduction of repolarization lability is associated with increased susceptibility of arrhythmogenesis in patients with prolonged QT and/or structural heart disease. With a high cytoplasmic CaBecause the electrophysiological, Ca