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

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 I Na , I Ca, L , and I kur current densities. We observed that NRG-1 could reduce APD, atrial fibrosis, levels of CRP and NE, I Na and I Ca, 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, I Na and I Ca, L current densities, Nav1.5 and Cav1.2 expression levels, elevated AF inducibility, Ach levels, I kur 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.