β-AR (β-adrenergic receptor) stimulation is known to exacerbate arrhythmias, and activation of PKG (protein kinase G) is widely accepted to antagonize the effects of β-AR stimulation.22–24 Therefore, the initial aim of this study was to determine whether activation of the PKG pathway, using the PDE5 (phosphodiesterase 5) inhibitor sildenafil to increase cGMP, was protective against long QT arrhythmias and whether this involved alterations in Ca2+ release from the SR and thence prevention of triggered arrhythmias. The gene discussed is PDE5A; the disease is Arrhythmia.