Suppression of Arrhythmia by Enhancing Mitochondrial Ca2+ Uptake in Catecholaminergic Ventricular Tachycardia Models
Maria K. Schweitzer, Fabiola Wilting, Simon Sedej, Lisa Dreizehnter, Nathan J. Dupper, Qinghai Tian, Alessandra Moretti, Ilaria My, Ohyun Kwon, Silvia G. Priori, Karl-Ludwig Laugwitz, Ursula Storch, Peter Lipp, Andreas Breit, Michael Mederos y Schnitzler, Thomas Gudermann and Johann Schredelseker
MiCUps Reduce Episodes of Ventricular Tachycardia in RyR2R4496C/WT Mice
Three-lead surface ECGs from RyR2R4496C/WT mice receiving efsevin or kaempferol through an osmotic minipump are shown. After a baseline ECG was recorded, mice were injected with epi/caff as an adrenergic stimulus. Basic parameters of the ECG like PR (A), QT (B), and QRS (C) intervals were comparable between the vehicle-treated group and both of the MiCUp-treated groups at baseline and after epi/caff challenge (Kruskal-Wallis test). (D) Heart rate increased upon administration of epi/caff in all 3 groups but remained unaffected by the administration of MiCUps (Kruskal-Wallis test). (E) Examples of a normal ECG recording and a recording showing bidirectional ventricular tachycardia. (F) Episodes of bidirectional ventricular tachycardia were recorded in 11 of 11 vehicle-treated mice but were significantly reduced to 6 of 10 in mice with efsevin and 6 of 11 in mice with kaempferol (p = 0.035, Fisher’s exact test). ECG = electrocardiography; epi/caff = epinephrine/caffeine; MiCUp = mitochondrial calcium uptake enhancer.