β₃-Adrenoceptor Mediates Metabolic Remodeling In The Rabbit Model Of Tachypacing-induced Atrial Fibrillation

Background Atrial fibrillation (AF) has its own progress and continuity, structural, electrical, neurological and functional remodeling occurs with AF,and reconstructed occur, maintain and progress of the remodeling is closely related with the energy metabolism reconstructed. β3-AR is closely related with energy metabolism in heart failure,it also upregulate in AF, while its role in the AF remains unclear.Objective This study aimed to observe β3-adrenergic receptor inhibitors and agonists intervention in rabbit with energetic metabolism in tachypacing-induced atrial fibrillation (AF),to investigate and observe the impact and mechanisms of β3-AR in the energy metabolism remodeling in atrial fibrillation.Methods In this study,16 rabbits were randomly divided into 2 subgroups:1) the Blank control group:eight,2)experiment group:eight. Intubation while thoracotomy suture in the right atrial appendage bipolar electrode, and placement atemporary pacemake in the subcutaneousr,and given the remaining three groups of 600 beats/min rapid atrial pacing seven days except the blank control group.After successful modeling,ECG were used to monitor the induction of AF and atrial effective refractory period (AERP).Western blot (western-blot) and real-time quantitative PCR (real-time RT-PCR) method is applied to detect β3-AR expression of the atrial muscle groups of rabbits, simultaneous detect the change of the key enzymes of metabolic regulation of peroxisome proliferator-activated receptors γ(PPARγ).The kit detects the content change of ATP, lactic acid (LD), succinate dehydrogenase (SDH),Na+ K+ ATP enzyme, Ca2+ Mg2+ ATPase and total ATP enzyme in metabolic process.Results Result showed that β3-AR was significantly up-regulated in the AF rabbits. Compared with the blank control group, pacing seven days group AERP shortening(71.67±5.77 vs.95.00 ± 5.00 ms, p< 0.01),ATP content decreased, the LD decreased (0.37±0.08vs.0.68±0.16, P<0.05), total ATP enzyme(7.39±1.069vs. 16.35±0.97, P<0.01), Na+K+ATPase (10.06±1.31 vs.14.54±0.24,P<0.01), Ga2+ Mg2+ ATPase (4.68±1.19vs.8.61±1.65,P<0.05) and SDH (1.66±0.13vs.3.16±0.32,P<0.05) expressions decreased.The myocardial tissue Substrate Utilization changes and Metabolic refactoring appears.Furthermore, key regulators of metabolism, peroxisome proliferator-activated receptor-γ (PPAR-γ) decreased in the AF rabbits but increased after SR59230A infusion, suggesting an involvement of PPARy Speculate that PPARy signaling pathway involved β3-AR-mediated metabolism reconstructed in AF.Conclusons β3-AR excitement (or suppression) can promote (or slow down) energy metabolism reconstruction in rapid atrial pacing of the rabbit model,and plays the role of deterioration (or protection) in AF..