Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes

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). Conclusions 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.