| Objective: With the aging of the population and the change of lifestyle,the morbidity of diabetes mellitus(DM)is increasing.Diabetes mellitus is an independent risk factor for atrial fibrillation(AF).However,the mechanisms of atrial fibrillation related to diabetes is needs further research.Mitochondrial dysfunction and oxidative stress are involved in the pathophysiological process of diabetic patients with atrial fibrillation.In the following research,we investigated the effects of apocynin,an inhibitor of NADPH oxidase,on atrial remodeling and AF-inducibility in diabetic rabbits,and the protective effects of apocynin on atrial mitochondrial dysfunction.Methods: Forty-eight Japanese rabbits were randomized into two groups following the establishment of the diabetic models: alloxan-induced diabetic group(D group),diabetes with apocynin treatment group(DA group,n=24 for each group),other 24 rabbits as controls(C group).Rabbits in the DA group were orally administered apocynin for 8 weeks(15mg/kg/day).All the rabbits were fed in the same environment.Their weight and glucose were measured every week.After 8 weeks,rabbits in each group were randomly selected for following experiments: 1.Echocardiography,hemodynamics and histological study were performed.Histological experiments contain HE staining and Masson staining.2.The Langendorff perfusion system was used to establish the perfusion model.Firstly,Mapping Lab system was used to record the conduction velocity and inhomogeneity index heterogeneity of left and right atrium.Then,four sets of bipolar electrodes were placed on the epicardial surface of the heart.Interatrial conduction time(IACT),wenckbach cycle length of AV conduction(AVWCL),atrial effective refractory period(AERP)were measured,and Atrial effective refractory period dispersion(AERPD)was calculated.Burst stimulation and S1S2 stimulation were used to induce AF,and the frequency and duration of AF induction were recorded,and the rate of AF induction was calculated.3.Mitochondrial respiratory control rate(RCR)was assessed.Result: 1.Compared with C group,left atrial diameter(LAD),interventricular septal thickness(IVST)and left ventricular posterior wall thickness(LVPWT)were increased in DM group(P < 0.05),and the LAD,IVST and LVPWT were all decreased in DA group(P < 0.05).The left ventricular ejection fraction(LVEF)of DM group and DA group was significantly lower than that of C group.Apocynin can not improve LVEF.There was no statistical difference in hemodynamic indexes of rabbits in each group.The results of surface ECG showed that the heart rate(HR)of DM group and DA group was lower than that of C group(P < 0.05).2.HE staining showed that the arrangement of myocardial cells in DM group was disordered,inflammatory cell infiltration was observed,and the cell morphology in DA group was improved.The left atrial collagen volume fraction(LACVF)in DM group was higher than others(P < 0.01).3.The conductive velocity were lower in DM group than others(P<0.05).The inhomogeneity index was increased in DM group than others(P<0.05).Interatrial conduction time(IACT)at basic cycle length of 200 ms and 250 ms in DM group were longer than in C and DA group(P<0.01).Also,atrial effective refractory period dispersion(AERPD)in D group was longer than in others(P<0.01).The AF-inducibility in DM group was significantly higher than others(P < 0.01).4.The DM group showed a decreased RCR value than other two groups(P<0.01).Conclusion: Apocynin can improve atrial substrate,reduce atrial fibrosis,improve atrial electrical remodeling and reduce the AF-inducibility in diabetic rabbits,and improve mitochondrial respiratory function. |
PDF Full Text Request