After 12 weeks of alcohol intake, the mice were subjected to atrial burst pacing. Alcohol treatment increased the inducibility and duration of AF (Fig. 1B–D). Further atrial electrical mapping results revealed aberrant atrial electrical conduction pattern in alcohol group as evidenced by significantly decreased mean conduction velocity and increased absolute inhomogeneity as well as inhomogeneity index (Fig.1E-H). These data showed that excessive alcohol intake led to marked atrial electrical remodeling. Interestingly, exogenous SIRT3 activation attenuated these effects by reducing AF inducibility and duration, decreasing prolonged atrial conduction time and ameliorating the inhomogeneity of atrial electrical conduction (Fig. 1 B–H). Next, alcohol intake caused marked enlargement of atria by increasing LA diameter and diastolic area (Fig. 1I–K), which was effectively attenuated by SIRT3 activation. Furthermore, we investigated the effect of these treatments on left ventricular (LV) function. As shown in Fig. S1, Alcohol intake impaired LV performance by decreasing LVEF and LVFS, which was partially inhibited by SIRT3 overexpression. Taken together, these data revealed that SIRT3 signaling might play a key role in regulating atrial electrical remodeling and atrial function in alcohol-treated animals.

SIRT3 overexpression attenuated atrial electrical remodeling and atrial enlargement in alcohol consumption group. (A) A schematic illustration of the experimental groups and protocols. (B)Representative segments of electrocardiogram recordings during and after burst pacing. Solid line indicated burst pacing period. Sinus rhythm period was indicated by black dashed line while AF period was highlighted by red line. (C) Inducibility of AF (n = 12). (D) Duration of AF. The duration of AF was quantified by the longest duration of atrial arrhythmia episodes in each animal. (E) Representative electrophysiological maps in left atria during sinus rhythm. Bars indicated the time from the first to the last measurement during one heartbeat. Arrows showed the direction of electrical conduction in left atrial surface. (F–H) Summary of the left atrial conduction during sinus rhythm. Mean conduction velocity, absolute inhomogeneity and inhomogeneity index of left atria were calculated by electrophysiological mapping system with the accompanying software. (I) Representative M-mode images by echocardiography. Left atrial diameter and area were highlighted. (J, K) Summary of the left atrial dimension. LA diameter and diastolic area were calculated during sinus rhythm. The results were expressed as the mean ± S.E.M., n = 6 per group. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

BBA-Molecular Basis of Disease

10.1016/j.bbadis.2022.166483