As shown in Fig. 2A and B, Ang II-infusion increased the inducibility and duration of AF, while this was attenuated by BT2 treatment. Meanwhile, the electrophysiological mapping experiment showed that Ang II significantly decreased mean atrial epicardial conduction velocity and increased absolute inhomogeneity as well as inhomogeneity index of left atrium (Fig. 2C and D). These effects were also suppressed by BT2 administration, indicating that atrial BCAA catabolic dysfunction probably played a key role in the pathogenesis of AF. Importantly, the similar beneficial effects were observed in melatonin-treated mice (Fig. 2A–D). Next, the echocardiographic data exhibited that BT2 or melatonin treatment attenuated Ang II-induced LA chamber enlargement (Fig. 2E and F). Meanwhile, BT2 or melatonin treatment also increased LVEF and LVFS, and decreased LV mass (compared with the Ang II group, Fig. S2).
Fig. 2. The effect of BT2 and melatonin on Ang II-induced atrial electrical remodeling. (A) simultaneous recordings of intracardiac atrial electrogram (left part) and surface electrocardiogram (right part) after 4-week infusion of Ang II (2000 ng/kg per minute). Solid underlines indicate burst pacing period while dashed underlines highlight AF period. (B) inducibility of atrial fibrillation (n = 8, left). The duration of AF (n = 5, right) was quantified by the longest atrial arrhythmia episodes of each animal. (C) representative electrophysiological mapping images of spontaneous conduction in left atrium (from red to blue, bars indicate the total time from the first to the last measurement within one heart beat). (D) mean conduction velocity, absolute inhomogeneity and inhomogeneity index of left atrial electrical conduction (n = 5). (E) representative echocardiography of left atrial (LA) chamber. Solid underlines indicate LA diameter (parallel to the mitral valve annulus). (F) quantification of LA diameter (n = 5). **P < 0.01/*P < 0.05 vs. control group. ^^P < 0.01/^P < 0.05 vs. Ang II group. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Free Radical Biology and Medicine
https://doi.org/10.1016/j.freeradbiomed.2021.11.043
