Why the study?
Does phospholamban ablation prevent arrhythmias in mice with CaMKII-constitutive phosphorylation of RyR2 at site S2814?
Population
3- to 4-month-old male mutant mice with phospholamban ablation, RyR2-S2814D+/+ knock-in mice, and mice…
Comparison
Phospholamban (PLN) ablation (genetic knock-out) vs S2814D+/+ mice and wild-type mice
Design
Preclinical
Key result
Phospholamban ablation completely offset the high incidence of sustained bidirectional ventricular tachycardia seen in S2814D+/+ mice (0/6 vs 4/5, p<0.05) after catecholaminergic challenge.
Authors
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Phospholamban ablation offsets CaMKII-driven arrhythmias in this mouse model; leaves open whether SR Ca2+ uptake enhancement merits clinical investigation.
Does phospholamban ablation prevent arrhythmias in mice with CaMKII-constitutive phosphorylation of RyR2 at site S2814?
Absolute Event Rate: 0% vs 80%
Absolute Risk Reduction: 80%
p-value: p=<0.05
Increasing SR Ca2+ uptake by phospholamban ablation can prevent arrhythmic events triggered by SR Ca2+ leak due to CaMKII-dependent phosphorylation of the RyR2-S2814 site.
Mazzocchi et al. (2015) studied Ventricular arrhythmias. Phospholamban (PLN) ablation vs. S2814D+/+ mice (no PLN ablation) was evaluated on Incidence of sustained bidirectional ventricular tachycardia after catecholaminergic challenge (p=<0.05). Phospholamban ablation completely offset the high incidence of sustained bidirectional ventricular tachycardia seen in S2814D+/+ mice (0/6 vs 4/5, p<0.05) after catecholaminergic challenge.