Mechanisms associated with the development of atrial fibrillation after sepsis and the role of neuregulin-1

Abstract

Abstract Purpose To explore the mechanisms involved in the development of atrial fibrillation (AF) after sepsis and examine the effect of neuregulin-1 (NRG-1) on AF and related mechanisms. Methods We used cecal ligation and puncture (CLP) to establish the sepsis model. NRG-1 was administered via the tail vein at a dose of 0.01µg/g 12 and 24 h postoperatively to determine its effect on AF after sepsis. Results Compared with Sham rats, septic rats exhibited enhanced AF inducibility, atrial fibrosis, norepinephrine (NE), and C-reactive protein (CRP) levels, reduced action potential duration (APD), atrial effective refractive period (AERP), acetylcholine (Ach) levels, expression of Nav1.5, Cav1.2, and Kv1.5, and significantly decreased INa, ICa, L, and Ikur current densities. We observed that NRG-1 could reduce APD, atrial fibrosis, levels of CRP and NE, INa and ICa, L current densities, and expression levels of Nav1.5 and Cav1.2, however, it failed to prevent the onset of AF. Compared with the Sham group, the Sham + NRG-1 group rats showed a reduction in APD, AERP, INa and ICa, L current densities, Nav1.5 and Cav1.2 expression levels, elevated AF inducibility, Ach levels, Ikur current density, and Kv1.5 expression. Conclusion Sepsis can induce tissue and electrical remodeling in the atria and promotes the development of AF. NRG-1 could attenuate the degree of atrial fibrosis and organismal inflammation in sepsis while promoting the development of AF in Sham rats, impacting atrial electrophysiology and ionic currents.