Subcutaneous BNP Injections in Rabbits: A Novel Approach to Mitigate Myocardial Remodeling in Atrial Fibrillation.

Abstract

Background: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with increased morbidity and mortality, highlighting the need for novel therapeutic strategies. This study aimed to evaluate the effects of B-type natriuretic peptide (BNP) on cardiac structural remodeling in a rabbit model of AF.

Methods: Rabbits were subjected to rapid pacing to induce an AF model, and BNP was delivered subcutaneously at a dose of 20 μg/kg/d twice per day for three weeks. Electrophysiological measurements were taken to assess the AF induction rate and atrial effective refractory period (AERP), while echocardiographic measurements evaluated left atrial size and function. Histological examinations included hematoxylin and eosin (H&E) staining and Masson's trichrome staining to observe myocardial tissue structure and fibrosis. The ultrastructure of myocardial tissue was observed using a transmission electron microscope.

Results: The study found that BNP treatment significantly reduced the AF induction rate (p < 0.001), improved AERP (p < 0.001), and ameliorated structural and functional changes in the left atrial (p < 0.05). Histological analysis demonstrated decreased myocardial fibrosis post-BNP treatment (p < 0.05). Results also showed that BNP attenuated the cardiomyocyte remodeling caused by AF, as evidenced by significant effects on the expression levels of transforming growth factor-β 1 (TGF-β1), tissue inhibitors of matrix metalloproteinases 1 (TIMP1), matrix metalloproteinase 9 (MMP9), and Collagen I/III (p < 0.05).

Conclusion: These findings suggest that subcutaneous injections of BNP may serve as an effective therapeutic agent in mitigating cardiac structural remodeling in AF, offering significant clinical implications for treating this condition.