The Effect Of Ivabradine In With Age-related Atrial Fibrillation

Objective:to investigate the effect of Ivabradine on electrophysiology of atrial myocytes in dogs with atrial fibrillation.Methods:18 old beagle were randomly divided into old age group(implanted pacemaker,but not open),the elderly atrial fibrillation group(6,implanted pacemaker rapid atrial pacing,8 weeks),the mine cut set group(6,implanted pacemaker rapid atrial pacing,8 weeks,giving Ivabradine drug intervention in 2 weeks(measurement of 2 mg/kg/d).The effective refractory period(ERP)of atria and pulmonary veins was measured by S1S2 decreasing stimulation for each beagle before and after administration,and the atrial fibrillation induction rate and duration were measured by Burst stimulation.After the administration,the mRNA levels of MMP-9 and TIMP-1 in atrial muscle and pulmonary vein were detected by fluorescence quantitative PCR,and the protein levels of MMP-9and TIMP-1 were detected by western-blotting.The changes of MCP-1 in atrial tissue were determined by ELISA.The whole cell patch clamp technique was used to detect the change of If current density on the thin surface of a single atrial muscle.Results:1)compared with elderly atrial fibrillation group,the upper left pulmonary vein mine cut set group ERP [(126 ±4.17)VS(139 ±4.67),ms,P < 0.05)and left atrial ERP [(124± 4.59)VS(138 ±3.47),ms,ms P < 0.05)significantly increased,and af duration [(135± 4.89)s VS(49.8±5.71)s,P < 0.05),atrial fibrillation induced rate [100%(60/60)VS 41%(25/60),P < 0.05)significantly reduced;2)when the whole cell If current was recorded,the If current of atrial myocytes in the aged dogs with atrial fibrillation was significantly increased(5.79±0.60pA/pF vs3.18±0.30pA/pF,P < 0.01)compared with that in the aged dogs with sinus rhythm group.Compared with the aged dogs with atrial fibrillation group,the current of atrial myocytes in the Ivabradine group was significantly reduced to(2.87±0.63pA/pF,P < 0.01).3)compared with the elderly atrial fibrillation group,the mRNA level of MMP-9 in the left atrium of the Ivabradine group was significantly decreased to(3.15±0.32 VS 2.38±0.29,P < 0.05),while the level of TIMP-1 was significantly increased to(1.22±0.17 VS 2.34±0.19).Compared with the elderly atrial fibrillation group,the protein expression level of MMP-9 in the left atrium of the Ivabradine group was significantly decreased to(0.72±0.03VS0.41±0.04,P < 0.05).The protein expression level of TIMP-1 was significantly increased to(1.19±0.16 VS 2.07±0.2,P < 0.05).4)compared with the elderly af group,the MCP-1 level of the ivabridine group was significantly reduced to(734±65 VS 551±73,P < 0.05).Conclusion: 1)by inhibiting the If current density of atrial myocytes,ivabradine can prolong the effective refractory period of atrial fibrillation,reduce the induction rate of atrial fibrillation,and shorten the duration of atrial fibrillation.Ivabradine has a potential protective effect on aging atrial fibrillation.2)by inhibiting oxidative stress,Ivabradine down-regulates MCP-1,regulates the mRNA and protein expression of MMP-9 and TIMP-1 in atrial tissue,and promotes the restoration of balance,which may be one of the molecular mechanisms of Ivabradine to improve the aging of atrial fibrosis and inhibit atrial fibrillation.