Cardiovascular Research Laboratories, School of Physiology & Pharmacology, University of Bristol, Bristol, UK.
Circ Arrhythm Electrophysiol. 2011 Oct;4(5):761-9. doi: 10.1161/CIRCEP.111.964783. Epub 2011 Aug 23.
Although arterial hypertension and left ventricular hypertrophy are considered good epidemiological indicators of the risk of atrial fibrillation (AF) in patients, the link between elevated afterload and AF remains unclear. We investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats.
Male Wistar rats (aged 3-4 weeks) were anesthetized and subjected to either partial stenosis of the ascending aorta (AoB) or sham operation (Sham). Experiments were performed on excised hearts 8, 14, and 20 weeks after surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5×5 electrode array. Cryosections of left atrial tissue were retained for histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed marked left atrial hypertrophy and fibrosis at 14 and 20 weeks postsurgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks postsurgery. The substrate for arrhythmia was associated with reduced vectorial conduction velocity and greater inhomogeneity in conduction but without changes in effective refractory period. Left atrial expression of the gap junction protein, connexin43, was markedly reduced in AoB compared with Sham hearts.
Using a small-animal model, we demonstrate that elevated afterload in the absence of systemic hypertension results in increased inducibility of AF and left atrial remodeling involving fibrosis, altered atrial connexin43 expression, and marked conduction abnormalities.
尽管动脉高血压和左心室肥厚被认为是房颤（AF）风险的良好流行病学指标，但升高的后负荷与 AF 之间的联系仍不清楚。我们在大鼠升高后负荷的手术模型中研究了心房重构和心律失常的基质。
雄性 Wistar 大鼠（3-4 周龄）麻醉后接受升主动脉部分狭窄（AoB）或假手术（Sham）。手术后 8、14 和 20 周在离体心脏上进行实验。使用 5×5 电极阵列从灌流心脏的心外膜表面记录单极电图。保留左心房组织的冷冻切片用于组织学和免疫细胞化学分析。与 Sham 相比，AoB 心脏在手术后 14 和 20 周显示出明显的左心房肥厚和纤维化。AoB 大鼠心脏在手术后 20 周起搏诱导 AF 的发生率和持续时间增加。心律失常的基质与向量传导速度降低和传导异质性增加有关，但有效不应期无变化。AoB 心脏中缝隙连接蛋白 connexin43 的左心房表达明显低于 Sham 心脏。
使用小动物模型，我们证明了在没有系统性高血压的情况下升高的后负荷导致 AF 的诱导率增加和左心房重构，涉及纤维化、心房 connexin43 表达改变和明显的传导异常。
