Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation
Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation
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DOI：
10.1016/j.yjmcc.2008.11.012
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发表时间：
2009-03-01
影响因子：
5
通讯作者：
Schotten, Ulrich
中科院分区：
文献类型：
--
作者：
Greiser, Maura;Neuberger, Hans-Ruprecht;Schotten, Ulrich
心房扩张是患有或不患有心房颤动（AF）的患者发生血栓栓塞的独立危险因素。在许多患者中，心房扩张伴随着扩张的心房的收缩功能下降。虽然先前已经解决了导致颤动心房中心房收缩功能障碍的一些机制，但扩张心房中心房收缩重塑的细胞和分子机制尚不清楚。本研究表征了心房扩张山羊模型中的体内心房收缩功能，并将其与 AF 山羊模型进行了比较。通过研究心房肌束中的收缩功能、电生理学和肌浆网 (SR) Ca2+ 负荷，并分析关键 Ca2+ 处理蛋白、肌丝的表达和磷酸化水平及其上游调节因子的表达和活性，阐明了潜在机制的差异。在 7 只长期使用仪器的清醒山羊中，在 AV 结消融（AV 阻滞山羊 (AVB)）后 3 周进行性心房扩张期间监测其心房收缩功能障碍。在开胸实验中，测量了心房做功指数 (AWI) 和不应性（10 只患有 AVB 的山羊，5 只患有由重复心房突发起搏 (AF) 诱发的 10 天 AF 的山羊，10 只对照山羊）。研究了右心房肌束的等长收缩力 (FC)、跨膜动作电位 (AP) 和快速冷却挛缩（RCC，SR Ca2+ 负荷的测量方法）。通过蛋白质印迹法对总 Ca2+ 处理和磷酸化 Ca2+ 处理以及肌丝蛋白水平进行定量。在 AVB 山羊中，心房大小增加了 18%（从 26.6 +/- 4.4 到 31.6 +/- 5.5 毫米，n=7 p）
Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca2+ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca2+-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca2+ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca2+-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6 +/- 4.4 to 31.6 +/- 5.5 mm, n=7 p