Self-terminating AF depends on electrical remodeling while persistent AF depends on additional structural changes in a rapid atrially paced sheep model
Self-terminating AF depends on electrical remodeling while persistent AF depends on additional structural changes in a rapid atrially paced sheep model
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DOI：
10.1016/j.yjmcc.2007.05.010
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发表时间：
2007-08-01
影响因子：
5
通讯作者：
Heidbuchel, Hein
中科院分区：
文献类型：
--
作者：
Anne, Wirn;Willems, Rik;Heidbuchel, Hein
心房颤动（AF）的发展与电和结构重塑有关。本研究的目的是在快速心房起搏绵羊模型（有或没有希氏束消融）中评估电和结构重塑对 AF 发展的贡献，并确定血管紧张素途径和基质金属蛋白酶在此过程中的作用。 35 只羊在心房中快速起搏，并随机接受希氏束消融术 (HBA)（21 只羊；HBA 羊）或不接受希氏束消融术（14 只羊；非 HBA 羊）。 HBA 后心室起搏速度为 80 bpm。两组均被细分为接受积极治疗（喹那普利+氯沙坦）或安慰剂。绵羊被追踪了 15 周。诱发性 AF 定义为持续 > 1 分钟的快速不规则心房节律。如果在进一步随访期间不再记录窦性心律 (SR)，则认为诱发性房颤是持续性的。房颤诱发房颤的可能性在 4 组之间没有差异。另一方面，非 HBA 绵羊明显早于 HBA 绵羊出现持续性 AF (p=0.028)。他们的心室率升高、心房 MMP-2 减少、TIMP-2 表达增加以及更广泛的心房纤维化。对这些绵羊进行积极治疗可显着降低 AT-II (p=0.018)，防止心房纤维化 (p < 0.001)，并减缓持续性 AF 的发展 (p=0.049)。电重塑足以诱发房颤，而持续性房颤则需要结构改变。我们模型中的纤维化发展是 AT-II 表达增加与 MMP 表达变化相结合的结果。抑制血管紧张素通路可抑制心房纤维化和持续性房颤的发展。 (c) 2007 Elsevier Inc. 保留所有权利。
The development of atrial fibrillation (AF) is associated with electrical and structural remodeling. The aim of this study was to assess the contribution of electrical and structural remodeling to the development of AF in a rapid atrially paced ovine model with and without His bundle ablation and to determine the role of the angiotensin pathway and matrix metalloproteinases in this process. Thirty-five sheep were rapidly paced in the atrium and were randomized to undergo His bundle ablation (HBA) (21 sheep; HBA sheep) or not (14 sheep; non-HBA sheep). After HBA the ventricles were paced at 80 bpm. Both groups were subdivided to receive active treatment (quinapril+losartan) or placebo. Sheep were followed for 15 weeks. Inducible AF was defined as a rapid irregular atrial rhythm lasting > 1 min. Inducible AF was considered to be persistent if during further follow-up no sinus rhythm (SR) was documented anymore. The inducibility of AF with atrial tachypacing was not different between the 4 groups. On the other hand, non-HBA sheep developed persistent AF significantly earlier than HBA sheep (p=0.028). They had elevated ventricular rates, diminished atrial MMP-2, increased TIMP-2 expression, and more extensive atrial fibrosis. Active treatment in these sheep significantly lowered AT-II (p=0.018), prevented atrial fibrogenesis (p < 0.001) and slowed the development of persistent AF (p=0.049). Electrical remodeling is sufficient to induce AF, while structural changes are needed for persistent AF. Fibrosis development in our model is the result of an increased expression of AT-II in combination with changes in MMP expression. Inhibition of the angiotensin pathway suppresses atrial fibrosis and the development of persistent AF. (c) 2007 Elsevier Inc. All rights reserved.