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. Author manuscript; available in PMC: 2018 Aug 18.
Published in final edited form as: Circ Res. 2017 Jul 3;121(5):549–563. doi: 10.1161/CIRCRESAHA.116.310396

Figure 7. Transient Notch activation predisposes to atrial arrhythmias.

Figure 7

A programmed pacing protocol that consists of a drive train (S1) followed by a single extrastimulus (S2) with coupling intervals of 20ms and 15ms was performed on each heart. Stimulation was performed near the pulmonary vein to mimic the site of origin of triggers in human arrhythmias. An episode of supraventricular tachycardia (SVT) was defined as a reentrant and/or fast, abnormal ectopic activity lasting one second or longer. iNICD mice demonstrate a significantly greater number of episodes of SVTs when compared with littermate controls (example activation map during a macro-reentrant arrhythmia, A, Supplemental Videos I, II, and III) in response to programmed pacing (B, 16.7±7.4% vs. 70±18.6%, P=0.04). SVT inducibility is represented as the percentage of electrical stimulations that successfully induced an episode of SVT at S2 coupling intervals of 20 ms (each heart stimulated 3 times) and 15 ms (each heart stimulated 3 times). Doxycycline was administered at 8 weeks of age to control (αMHC-rtTA (n=3 females, n=2 males) and tetO_NICD controls (n=1 male)) and experimental iNICD mice (αMHC-rtTA; tetO_NICD (n=3 females, n=2 males)) followed by a 2–3 month washout. Statistics were performed using an unpaired t test with Welch’s correction. A value of P<0.05 was considered statistically significant.