Alpha-Lipoic Acid Prevents Atrial Electrical and Structural Remodeling via Inhibition of NADPH Oxidase in a Rabbit Rapid Atrial Pacing Model

Background The pathogenesis of atrial fibrillation(AF) is complex, and the treatment method is still not satisfactory. A rapid atrial pacing (RAP) model was constructed to study the effects of alpha-lipoic acid (ALA) on electrical and structural remodeling, as well as its possible mechanism in rabbits.Methods A total of 30 rabbits were randomly divided into a sham-operated group (SHAM group), a rapid atrial pacing model group (RAP group) and an alpha-lipoic acid+rapid atrial pacing model group (ALA+RAP group). Their right atriums were paced at a speed of 600 beats/min for 12 h in the RAP and ALA+RAP groups, and the atrial effective refractory period (AERP) and AERP frequency adaptability were determined during the pace. In each group, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected to observe the effects of oxidative stress. The pathological structure of the atrial tissue was observed through HE and Masson staining. Ultrastructural changes in the atrial myocytes were observed by transmission electron microscopy (TEM), and the expression levels of Nox2 and Nox4 were detected by immunohistochemistry, western blot and ELISA.Results Through testing AERP and AERP frequency adaptability, it was found that in the early stage of rapid atrial pacing, AERP gradually shortened, while ALA injection could remarkably delay this process. Correspondingly, AERP frequency adaptability in the RAP group was reduced, and ALA could enhance it. HE staining showed that pathological changes in the ALA+RAP group were milder than those in the RAP group. And it was found that in the ALA+RAP group, the deposition of collagen in the endomysium was remarkably reduced via Masson staining. Ultrastructure injury in the ALA+RAP group showed various degrees of improvement compared with the RAP group. RAP was accompanied by an increase in oxidative stress levels, and ALA could effectively inhibit RAP-induced oxidative stress in vivo via detecting SOD, MDA and ROS. In addition, Western blot showed that the expression of NOX2 and NOX4 was upregulated in RAP group, but ALA intervention could inhibit their expression. Moreover, immunohistochemistry and ELISA also got similar results as Western blot.Conclusion ALA can inhibit atrial electrical remodeling and structural remodeling by reducing ROS production and alleviating oxidative stress injury induced by rapid right atrial pacing, and its mechanism may be related to inhibiting the activity of NADPH oxidase.