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 p
Feng-Xiang Zhang Ming-Long Chen Bing Yang Wei-Zhu Ju Hong-Wu Chen Dong-Jie Xu Chun Chen Ke-Jiang Cao
Objective:To investigate the effect of cardiomyocyte proliferation induced by human hepatocyte growth factor(HGF)in pigs with chronic myocardial infarction(CMI).Methods:A steerable,deflectable 7F catheter incorporating a 27-guage needle was advanced percutaneously to the left ventricular myocardium of 18 pigs with CMI.Pigs were randomized(1:1:1)to receive adenoviral vector HGF(total dose,1×10^10 genome copies),which was administered as five injections into the infarcted myocardium(total,1.0 mL),or saline,or Ad-null(control groups).Injections were guided by Ensite NavX left ventricular electroanatomical mapping.HGF and cyclin proteins were detected by western blot and immunoprecipitation analysis.Histological and immunohistochemical analysis determined proliferating cardiomyocytes.Myocardial perfusion and cardiac function were estimated by Gated-Single Photon Emission Computed Tomography(G-SPECT).Results:Western blot analyses showed that HGF were predominantly expressed in the infarct core and border in the myocardium of the infarcted heart.G-SPECT analysis indicated that the HGF group had better cardiac function and myocardial perfusion four weeks after the injection of Ad-HGF than before the injection of Ad-HGF.After treatment there were more proliferating cardiomyocytes in the HGF group compared to either of the control groups.Furthermore,the HGF group myocardial samples expressed higher levels of p-Akt,cyclin A,cyclin E,cyclin D1,cdk2,cdk4 than those in the control groups.Conclusion:The over-expression of HGF activates pro-survival pathways,induces cardiomyocyte proliferation,and improves the perfusion and function of the porcine CMI heart.
心律失常是临床上最常见的疾病之一,是当今心脏疾病领域中的一大难题。无论是药物治疗还是非药物治疗,都有很多问题需要解决。近年来研究显示血管紧张素转换酶抑制剂(ACEI)、血管紧张素受体阻滞剂(ARB)、醛固酮受体拮抗剂、他汀类药物、不饱和脂肪酸等心律失常上游药物(upstream medical agents)均具有抗心律失常作用。