Reverse dedifferentiation of atrial cardiomyocytes after restoration of sinus rhythm from atrial fibrillation in goats

Objective Chronic atrial fibrillation (AF) results in dedifferentiation of atrial cardiomyocytes that plays an important role in the perpetuation of AF. In this study, we aimed to investigate the changes of titin and α-smooth muscle actin (α-SMA) after long time of AF reversal. Methods Twenty-four goats were randomized into four groups: (1) sinus rhythm (SR), (2) 3 months AF (3-mo AF), (3) 3 months SR after 3 months AF (3-mo post AF), (4) 6 months SR after 3-mo AF (6-mo post AF), with 6 in each group. By pacing on the anterior bottom of left atria appendage (LAA), we established a goat model of chronic AF. Atria effective refractory period (AERP) was measured with electrophysiological methods. Ultra-structure was studied with echocardiography, light and electron microscopy. Titin and α-SMA protein expressions were determined by Western blot. Results The animals underwent high rate pacing on LAA for a mean of 42.23 ± 21.70 days before presenting AF. Electrophysiological analysis revealed that AERP completely resumed in 3-mo post AF goats. Echocardiography displayed that the size of left atrium resumed almost in 6-mo post AF goats (P< 0.01). Pathological and electron microscopic examination revealed the disorder of myofibrils, augmentation of intercellular space, myolysis, accumulation of glycogen, and numerous bigger mitochondria among atrial cardiomyocytes in 3-mo AF goats. They recovered mostly in 6-mo post AF goats. Western blot showed that the band density of titin significantly reduced in 3-mo AF goats compared to SR ones 1826 ± 319 vs 5012 ± 854, P < 0.01. In 3- and 6-mo post AF goats, titin increased gradually and it reversed completely in 6-mo post AF goats (3841 ± 601 and 4523 ± 833 respectively, P < 0.01). Conversely, the band density of α-SMA was significantly higher in 3-mo AF goats (5324 ± 948) than in SR ones (1619 ± 271, P < 0.01). In 3- and 6-mo post-AF goats, α-SMA decreased gradually, and it recovered mostly in 6-mo post AF goats (4437 ± 792 and 2205 ± 540 respectively, P< 0.01,). Conclusions These data indicate that the reversal of dedifferentiation of atrial cardiomyocyts is a very slow process, and it is definitely essential for normal cardiac function.