Influence of Continuous Training on Atrial Myocytes I_K1 and I_KAch and on Induction of Atrial Fibrillation in a Rabbit Model

Abstract

Background Elucidation of mechanisms underlying continuous training-related atrial fibrillation (AF) may inform formulation of novel therapeutic approaches and training method selection. This study was aimed at assessing mechanisms underlying continuous training-induced AF in an animal model. Methods Healthy New Zealand rabbits were divided into three groups (n=8 each), namely, control (C), and moderate intensity (M), and high intensity (H) continuous training according to treadmill speed. Atrial size andintrinsic and resting heart rates were measured by transthoracic echocardiography before, and 8 and 12 weeks after training. Using a Langendorff perfusion system, AF was induced by S1S2 stimulation and the induction rate was recorded. Atrial IK1 and IKAch ion current densities were recorded using whole-cell patch-clamp technique in isolated atrial myocytes. Changes in atrial Kir2.1, Kir2.2, Kir3.1, and Kir3.4 mRNA expression were assessed by reverse transcriptase-coupled polymerase chain reaction. Results After 8 and 12 weeks, Groups M and H vs. Group C had greater (all P < 0.05) atrial anteroposterior diameter; greater incidence of AF (60% and 90% vs. 45%, respectively; P < 0.05, also between Groups H and M); and greater atrial IKAch current density. In Group H, Kir2.1 and Kir2.2 mRNA expression in the left and right atria was increased (P < 0.05, vs. Groups C and M) as was left atrial Kir3.1 and Kir3.4 mRNA expression (P < 0.05, vs. Group C). Conclusion In a rabbit model, continuous training enlarges atrial diameter leading to atrial structural and electrical remodeling and increased AF incidence.

Effects of different intensity endurance training on atrial fibrillation in Rats

“…Previous studies have indicated a significant positive correlation between high-intensity exercise or long-term endurance exercise and the incidence of atrial fibrillation. These studies have also confirmed that exercise can lead to atrial fibrosis, vagal enhancement, and ionchannel changes in atrial myocytes 10,11 . However, the relationship between low-intensity or moderate-intensity exercise and the incidence of atrial fibrillation, as well as its underlying mechanism, has not been explored.…”

“…However, for nonathletes, further data are required to understand the relationship between exercise and atrial fibrillation. Some animal studies have indicated that endurance training at high intensity can lead to increased fibrosis and ionchannel changes in atrial myocytes 10,11 . Atrial remodeling-characterized by fibrosis that irregularly separates the atrial myocyte groups and creates multiple internal reentries-plays a significant role in the development of atrial fibrillation 12 .…”

Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibilty in a canine model of elite exercise

“…As far as we know, however, relatively scanty data has been obtained in large animal models of endurance training and proarrhythmic risk. Two chronic exercise models have been reported in rabbit [13, 32] but no such study has been reported on dog or other large animals. On the contrary, the available data on dogs show that acute [33] or chronic [34, 35] exercise exerts beneficial effects preventing ventricular fibrillation caused by acute ischaemia by delayed preconditioning [33] or by restoring the distorted parasymphathetic/sympathetic balance seen after myocardial infarction [34, 36].…”

Prolonged duration of repolarization and decreased conduction velocity in the atrial myocardium after hypothermic ischemia-reperfusion may be related to expressions of inward rectifier potassium channel 2.1 protein and connexin 40

“…The main component of I k1 is the inward rectifier potassium channel 2.1 protein (Kir2.1). 6 When the expression of Kir2.1 decreases, the duration of action potential repolarization is prolonged to increase the risk of atrial arrhythmia. 7 In addition, the expression of gap junction proteins, mediating direct intercellular communication, plays an important part in the incidence and maintenance of arrhythmia.…”