The Influence Of Endurance Exercise Training For IK₁ And IK_Ach In Atrial Myocyte And Mechanism Of Atrial Fibrillation Related With Exercise

Objective:Atrial fibrillation(AF)is one of the most common arrhythmia in dail clinical practice. The prevalence of AF is higher in individuals who are involved in intenseand long-term endurance exercise training than that in general population. However, it remains unknown that the relationship between AF and atrial electrophysiological remodeling in endurance sport athletes. Since atrial enlargement and increased vagal nerve tone induced by endurance training may indeed facilitate the appearance of AF.We propose that the changed function of IK1 and IKAch may associate with atrial fibrillation. To test our hypothesis, endurance training rabbitmodel will be developed through different running training sessions on a treadmill. The morphology of atrial and heart rate wouldbe investigated.For electrophysiological measurements, functional alterations of IK1 and IKAch and the active potential will be recorded using the whole cell patch-clamp technique.Relative genes of IK1 and IKAch expression will be assessed with RT-PCR, which can show the molecularbiological evidence of the function change of IK1 and IKAch. We apply stimulation to atrial in rabbit isolated heart to assess the induce threshold of AF in different training rabbits. Furthermore, we compare the difference of induce threshold and the electricphysiology parameters before and after using agonist/antagonist of IKAch/IK1 to evaluate the relationships between these channels and AF. The results in this study may help in exploring the electrophysiological mechanism of endurance training induced AF and looking for medicine to prevent AF related with exercise. Methods:Forty-two Healthy New Zealand rabbits are divided into three groups, control group(n=14), moderated-intensity endurance exercise training group(n=14) and high-intensity endurance exercise training group(n=14). The control group did not do any exercise and other groups did treadmill running with different ntensity(for 1h or one-time exhaustive exercise)for 5d a week for 12 w.The size of atrium and Intrinsic heart rate and resting heart rate was detected by using echocardiogram before exercise and 8w and 12 w after exercise finished, Langendorff system is employed for isolated heart perfusion in all rabbits, and AF was S1S2 and induction rate of AF was recorded. The whoie cell patch-clamp technique was used to record left and right atrial IK1 and IKAch ioniccurrents. RT-PCR was applied to assess possible changes in cardiac gene expressions of Kir2.1、Kir2.2、Kir3.1 and Kir3.4 in left and right atrial tissue. Results:(1)Compare with control group, the left atrial anteroposterior diameter and righe atrial anteroposterior diameter increased in mid-intensity group and high-intensity group after 8w and after 12w(all P<0.05). Compared with mid-intensity group, the left atrial anteroposterior diameter and right atrial anter-oposterior diameter increased in high-intensity group after 8 w and after12 w(all P<0.05). Com-pared with control group, the incidence of AF increased in mid-intensity group(45% vs. 60%) and high-intensity group(45% vs. 90%, all P<0.01).(2) Compare with before exercise, RHR and IHR reduced in mid-intensity group and high-intensity group after exercise(P<0.05,however,their were not change greatly in control group. Compare with control group, isolated heart rate reduced in midintensity group and high-intensity group after 12 w(all P<0.05).(3) Compare with control and mid-intensity group, the incidence of AF increased in high-intensity group(P<0.05) in the role of Ach. Compare with sole Ach perfusion, ADP90 and ERP of atrial myocytes were prolonged in different concentrations Atropine or Ba CL2+Ach perfusion in all group(P<0.05),and the incidence of AF reduced, with the increased concentration of their the incidence of AF gradually reduced; Compare with controland mid-intensity group, ADP90 and ERP of atrial myocytes were ADP90 and ERP of atrial myocytes were prolonged in high-intensity group(P<0.05), but the incdence of AF increased in high-intensity group(P<0.05).(4) In left and right atriumthe densities of IKAch were increased in high-intensity group(P<0.003. respectively at-100 mv and +50mv, vs. control and mid-intensity group) the densities of IKAch were increased in mid-intensity group(P=0.001 respectively at +50mv, vs. control).(5) In left and righe atrium, Kir2.1 and Kir2.2 m RNA expression by semiquantitative PT-PCR was increased significantly in high-intensity group(P<0.05, vs. controland mid-intensity group),Compare withcontrol group, the left atrium Kir2.1 and Kir3.1 m RNA expression by semiquantitative PT-PCR was increased significantly in mid-intensity group(P<0.05);In left atrium,Kir3.1 and Kir3.4 m RNA expression by semiquantitative PT-PCR was increased significantly in high-intensity group(P<0.04,vs.control), Comparewith mid-intensity group, the left atrium Kir3.4 m RNA expression by semiquantitative PT-PCR was increased significantly in high-intensity group(P<0.05).Conclusions:Long-terms and high-intensity treadmill runling can enlarge atrial inner diameter,but reduce RHR and IHR, which resulting in effect on atrial structural remodeling and electrical remodeling,and increase AF incidence in rabbits.