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 oftitin and...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 oftitin and a-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-too 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-too 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 oftitin 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 ofa-SMAwas 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 .展开更多
Left bundle branch block(LBBB)causes a delay in left ventricular contraction with an unsynchronized ventricular systole.LBBB is an independent determinant of morbi-mortality mainly when associated with cardiomyopathy ...Left bundle branch block(LBBB)causes a delay in left ventricular contraction with an unsynchronized ventricular systole.LBBB is an independent determinant of morbi-mortality mainly when associated with cardiomyopathy and left ventricular dysfunction.[1] LBBB due to non-ischemic cardiomyopathy is considered non-reversible.Such irreversibility occurs because LBBB and cardiomyopathy act in a synergic manner in order to maintain both situations.However,there are a few reports in the literature showing that some patients have had an improvement in cardiac function with normalization of QRS and have experienced a reverse remodelling with pharmacological therapy only.[2–4]展开更多
基金Acknowledgement This work supported by the National Basic Research Program of China (973 Program, 2008CB517303), a grant from National Natural Science Foundation of China (30800464), a grant of pivot talents of medicine of Jiangsu Province (RC2007040), and a grant from Provincial Natu- ral Science of Jiangsu, China (BK2005218)
文摘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 oftitin and a-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-too 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-too 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 oftitin 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 ofa-SMAwas 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 .
文摘Left bundle branch block(LBBB)causes a delay in left ventricular contraction with an unsynchronized ventricular systole.LBBB is an independent determinant of morbi-mortality mainly when associated with cardiomyopathy and left ventricular dysfunction.[1] LBBB due to non-ischemic cardiomyopathy is considered non-reversible.Such irreversibility occurs because LBBB and cardiomyopathy act in a synergic manner in order to maintain both situations.However,there are a few reports in the literature showing that some patients have had an improvement in cardiac function with normalization of QRS and have experienced a reverse remodelling with pharmacological therapy only.[2–4]