Role Of Ivabradine In Acute Atrial Fibrillation

objective: To investigate the expression of HCN channels,HCN2 and HCN4,and the changes of hyper-activation currents(If)during atrial electric remodeling in acute atrial fibrillation(AF)and to evaluate the therapeutic effect of ivabradine on AF induced by rapid atrial pacing.Methods: Eighteen dogs were randomly divided into three groups:control group(n = 6),pacing group(n = 6)and pacing+iva group(n = 6).Theelectrocardiogram was recorded in the control group.In the pacing group and pacing+iva group,rapid pacing was delivered at right atrium for 6 hours and ivbradine(0.5mg/kg/h)was given to the latter through continuous intravenous infusion.After the successful operation,atria and atrial appendages of both left and right atria were harvested.Real-time PCR and Western-blotting were used to detect the expression of HCN2 and HCN4 at both mRNA and protein levels.Atrial myocytes were isolated from the left atrial appendages of the three groups by collagenase and the single-pipette whole-cell patch-clamp technique was used to record If in atrial myocytes respectively.Results: The average heart rate of the control group did not change with time.However,the heart rate was significantly increased in the pacing group and decreased in the pacing+iva group with time,respectively(P<0.01 in both).After 6 hours of rapid atrial pacing,the incidence rate(46.67% vs 14.67%)and the duration(700 ± 309.84 s vs 120 ± 58.99s)of atrial fibrillation were significantly higher in the pacing group than the control group(P<0.01 in all);whereas the incidence rate(8.67%)and the duration of atrial fibrillation(105 ± 51.67s)in pacing+iva group were significantly lowerthan those of the pacing group(P<0.01 in both).The effectiverefractory period in the control group did not change with time,but it became increasingly shorter in the pacing group(P<0.01).On the contrary,the effective refractory period becameincreasingly longer with continous pacing in the pacing+iva group compared to the pacing group(P<0.01).Compared with the control group,the mRNA expression of HCN2 and HCN4 in the left atrium(LA),right atrium(RA),left atrial appendage(LAA)and right atrial appendage(RAA)were significantly increased in the pacing group(P<0.01).The whole cell recording showed that the If current of atrial myocyte was significantly increased in the pacing group(5.19 ± 0.60 pA/pF)than the control group(2.68 ±0.30pA/pF)(P< 0.01),which was significantly decreased(2.17 ± 0.63 pA / pF)after the administration of Ivabradine compared to the pacing group(P<0.01).Conclusion: The expression of HCN2 and HCN4 at bothmRNA and protein levels were significantly increasedin acute AF.Ivabradine can reduce heart rate,prolong atrial effective refractory period,and reduce the incidence rate and shorten the duration of AF.Ivabradine decreases the occurrence of acute AFthrough inhibition of HCN2 and HCN4 expression,reduction of If current and suppression of atrial electrical remodeling.