Chronic obstructive pulmonary disease (COPD) increases the risk of atrial fibrillation (AF), however, its arrhythmogenic mechanisms are unclear. This study investigated the effects of COPD on AF triggers (pulmonary veins, PVs) and substrates (atria), and their potential underlying mechanisms. Electrocardiographic, echocardiographic, and biochemical studies were conducted in control rabbits and rabbits with human leukocyte elastase (0.3 unit/kg)-induced COPD. Conventional microelectrode, Western blotting, and histological examinations were performed on PV, left atrium (LA), right atrium, and sinoatrial node (SAN) preparations from control rabbits and those with COPD. The rabbits with COPD had a higher incidence of atrial premature complexes, PV burst firing and delayed afterdepolarizations, higher sympathetic activity, larger LA, and faster PV spontaneous activity than did the control rabbits; but they exhibited a slower SAN beating rate. The LA of the rabbits with COPD had a shorter action potential duration and longer tachyarrhythmia induced by tachypacing (20 Hz) and isoproterenol (1 μM). Additionally, the rabbits with COPD had higher fibrosis in the PVs, LA, and SAN. H89 (10 μM), KN93 (1 μM), and KB-R7943 (10 μM) significantly suppressed burst firing and delayed afterdepolarizations in the PVs of the rabbits with COPD. Moreover, compared with the control rabbits, those with COPD had lower expression levels of the β1 adrenergic receptor, Cav 1.2, and Na+/Ca2+ exchanger in the PVs; Cav 1.2 in the LA; and hyperpolarization-activated cyclic nucleotide-gated K+ channel 4 in the SAN. COPD increases atrial arrhythmogenesis by modulating the distinctive electrophysiological characteristics of the PVs, LA, and SAN.

Obesity is an important risk factor for atrial fibrillation (AF). Increased epicardial adipose tissue in obesity can enhance inflammation and plays an important role in the pathophysiology of AF. However, it is not clear whether epicardial adipocytes directly modulate the electrophysiological characteristics of atrial myocytes. Wholecell patch clamp was used to record the action potentials (APs) and ionic currents in isolated rabbit left atrium (LA) myocytes incubated with and without (control) isolated adipocytes from epicardial, retrosternal, or abdominal adipose tissues, or adipocytes-conditioned supernatant for 2-4 h. Compared to control LA myocytes (n = 22), LA myocytes incubated with epicardial (n = 17), retrosternal (n = 18), or abdominal adipocytes (n = 22) had longer (80 ± 3, 109 ± 6, 109 ± 6, and 110 ± 7 ms, p＼0.001) 90 % AP durations (APD90). LA myocytes incubated with epicardial adipocytes had a more-positive resting membrane potential (RMP) than control LA myocytes (-57 ± 1 mV vs. -63.4 ± 1.4 mV, p＼0.05). However, LA myocytes (n = 32) incubated with supernatant had longer APD90 (93 ± 3 ms, p＼0.05), but similar RMP values (-62 ± 2 mV, p[0.05) in comparison to control myocytes. Epicardial adipocyte-incubated LA myocytes had larger late sodium currents, L-type calcium currents, and transient outward potassium currents, but smaller delayed rectifier potassium and inward rectifier potassium currents than control LA myocytes. Moreover, isoproterenol (10 nM) induced a higher incidence (67 vs. 22 %, p＼0.05) of triggered beats in adipocytes-incubated LA myocytes (n = 12) than in control LA myocytes (n = 9). In conclusion, adipocytes can directly modulate the electrophysiological properties and ion currents, causing higher arrhythmogenesis in LA myocytes.

OBJECTIVES: This study was conducted to investigate the effects of thyroid hormone on the electrophysiological characteristics of pulmonary vein (PV) cardiomyocytes. BACKGROUND: Hyperthyroidism is an important etiology of paroxysmal atrial fibrillation (AF). Pulmonary veins are known to initiate paroxysmal AF. METHODS: The action potential and ionic currents were investigated in single rabbit PV and atrial cardiomyocytes with (hyperthyroid) and without (control) incubation of L-triiodothyronine using the whole-cell clamp technique. RESULTS: Compared with the control cardiomyocytes, hyperthyroid PV and atrial cardiomyocytes had shorter action potential duration. Hyperthyroid PV cardiomyocytes had faster beating rates (1.82 ± 0.13 Hz vs. 1.03 ± 0.15 Hz, p＜0.005) and a higher incidence of delayed afterdepolarization (beating: 92% vs. 6%, p＜0.0001; non-beating: 45% vs. 3%, p＜0.005). However, only hyperthyroid PV beating cardiomyocytes had a higher incidence of early afterdepolarization (46% vs. 0%, p＜0.0001). The ionic current experiments showed that hyperthyroid PV beating cardiomyocytes had larger densities of overall slow inward (2.72 ± 0.21 pA/pF vs. 2.07 ± 0.19 pA/pF, p＜0.05), overall transient outward (1.39 ± 0.21 pA/pF vs. 0.48 ± 0.08 pA/pF, p＜0.001) and steady state outward currents (0.78 ± 0.06 pA/pF vs. 0.58 ± 0.04 pA/pF, p＜0.05) on depolarization and larger transient inward (0.021 ± 0.004 pA/pF vs. 0.005 ± 0.001 pA/pF, p＜0.001) on repolarization. By contrast, the hyperthyroid PV non-beating cardiomyocytes had larger densities of overall transient outward (1.01 ± 0.14 pA/pF vs. 0.37 ± 0.07 pA/pF, p＜0.001), steady state outward (0.61 ± 0.06 pA/pF vs. 0.44 ± 0.04 pA/pF, p＜0.05) and transient inward currents (0.011 ± 0.002 pA/pF vs. 0.003 ± 0.001 pA/pF, p＜0.05). C0NCLUSIONS: Thyroid hormone changes the electrophysiological activity of the PV cardiomyocytes. Increased automaticity and enhanced triggered activity may increase the arrhythmogenic activity of PVs in hyperthyroidism.