OBJECTIVE:This study was aimed to assess mechanisms underlying continuous training induced atrial fibrillation (AF) in an animal model.METHODS:Healthy New Zealand rabbits were divided into three groups ( n=12 each): control group (C), moderate intensity group (M), and high intensity group (H). The intensity of continuous training was adjusted according to the treadmill speed. After 12 weeks of training, with a Langendorff perfusion system, AF was induced by S1S2 stimulation and the incidence was recorded. Changes in atrial kir2.1, kir2.2, type Ⅰ and Ⅲ collagen protein mRNA expressions were assessed by quantitative real-time PCR. Masson staining was used to assess the extracellular collagen volume fraction (CVF) .RESULTS:After 12 weeks, comparing with group C, groups M and H had greater ( P<0.05): CVF, incidence of AF ( P<0.05, also between Groups H and M), and atrial inward rectifier potassium current/channel (IK 1) . In Group H, kir2.1, kir2.2, type Ⅰ and Ⅲ collagen protein mRNA expressions in the left atrium were increased ( P<0.05, compared with Groups C and M).CONCLUSION:Long-term and high-intensity treadmill running could increase AF incidence in rabbits.

目的 阐明持续训练相关性心房颤动(AF)的机制,可能为制定新的治疗方法和选择训练方法提供信息.本研究旨在评估兔动物模型中持续训练诱发房颤的机制.方法 33只新西兰大耳兔随机分为三组(每组11只):对照组(Group C)、中强度耐力运动训练组(Group M)及高强度耐力运动训练组(Group H),于训练前、训练后8周、12周分别检测各组兔固有心率(IHR);全部训练结束后,各组随机各取6只,共18只兔采用离体心脏Langendorff系统进行1μm/L乙酰胆碱(Ach)+不同浓度阿托品溶液(0 mg/ml～0.002 mg/ml)灌注冠脉,在左心耳置入的电极分别记录相应的心房有效不应期(AERP)及90％动作电位时程(APD90);给予心房早搏程序刺激(S1S2)诱发房颤.灌流完后剪取兔左心房,经PT-PCR技术检测心房肌组织IKAch通道Kir3.1、Kir3.4的mRNA表达.取剩余各组5只实验兔,共15只运用全细胞膜片钳技术,记录心房肌细胞IKAch电流密度.结果 长期高强度的耐力运动训练16周后,Group H兔IHR明显低于其他两组;1μm/L Ach背景下,相同剂量阿托品作用下,随着运动强度的增加APD90、AERP相应缩短有统计学差异(Group H vs.Group C and M,P<0.001);同一组内,随着阿托品剂量的增加APD90、AERP相应延长,房颤发生率降低有统计学差异(P<0.05);Group H心房肌细胞IKAch电流密度高于其他两组(Group H vs.Group C、M,P<0.05),Group H心房组织Kir3.1、Kir3.4的mRNA表达量高于其他两组(Group H vs.Group C、M,P<0.05).结论长期的高强度耐力运动训练促进运动试验兔房颤发生.

Objective To establish the animal model of exercise atrial fibrillation (AF) and review its results. Methods Healthy adult New Zealand rabbits (n=24) were divided into control group, mid-intensity group and high-intensity group (each n=8). The control group did not do any exercises and other groups did treadmill running with different intensity (for 1 h or one-time exhaustive exercise) for 5 d a week for 12 w. The size of atrium was detected by using echocardiogram before exercise and 8 w and 12 w after exercise. After exercise finished, Langendorff system is employed for isolated heart perfusion in all rabbits, and AF was induced by using S1S2 and induction rate of AF was recorded. Results Compared with control group, the left atrial anteroposterior diameter and right atrial anteroposterior diameter increased in mid-intensity group and high-intensity group after 8 w and after 12 w (all P<0.05). Compared with mid-intensity group, the left atrial anteroposterior diameter and right atrial anteroposterior diameter increased in high-intensity group after 8 w and after 12 w (all P<0.05). Compared 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). Conclusion Long-term and high-intensity treadmill running can enlarge atrial inner diameter and increase AF incidence in rabbits.

心房颤动（房颤）是临床上最常见、最难以治疗的心律失常，也是心血管疾病死亡的重要原因。随着我国老龄化社会的到来，心电监测水平的提高，房颤的患病率不断增加。目前有大量关于房颤病理改变的研究，而其机制尚不明确。房颤模型的建立，为房颤机制的研究奠定基础。