【罂粟摘要】Cx43空间异质性是肥厚性心肌病代偿期多态性室性心动过速的致心律失常底物
Cx43空间异质性是肥厚性心肌病代偿期多态性室性心动过速的致心律失常底物
翻译：曹莹 编辑：佟睿 审核：曹莹
贵州医科大学 高鸿教授课题组
心室重构增加了患者快速性室性心律失常倾向和猝死风险。在大鼠慢性压力超载模型中，我们研究了致死性心律失常、心脏电重构和结构重构的机制，以及心肌肥厚早期代偿期的心律失常。
26只Wistar大鼠分为主动脉横断缩窄术组(TAC，n=13)或假手术组(sham，n=13)。术后4周先行超声心动图检查，随后Langendorff离体心脏灌注进行心外膜(208或455个位置)和透壁(30个位置)心室电标测，取心脏组织进行(免疫)组织学和分子分析。
TAC组大鼠心肌明显肥厚，左心室功能完好。TAC组心外膜传导速度(CV)相似，但传导方向分散。透壁CV指标中，TAC组(37.6 ± 2.9 cm·s-1)较假手术组(58.5 ± 3.9 cm·s-1;P ＜ 0.01)。刺激左室诱导出持续性多态性室性心动过速发生率：TAC组大鼠8/13，sham组大鼠0/13。室性心动过速时，心外膜电激活模式表现为早期心外膜激活位点和功能传导阻滞位点的变化；偶尔观察到心外膜折返性激活。TAC组的心肌胶原沉积明显高于sham组，但TAC组间致心律失常和非致心律失常动物间无明显差异。TAC组致心律失常的动物中，Connexin43 (Cx43)的表达呈现异质性的，Cx43表达减少非磷酸化Cx43比例增高。
在大鼠TAC肥厚性心肌病代偿期模型中，传导离散度与心律失常发生相关，Cx43异质性增加，非磷酸化Cx43替代正常Cx43。这些改变可能导致多态性室性心动过速易感性增强。
Spatial Heterogeneity of Cx43 is an Arrhythmogenic Substrate of Polymorphic Ventricular Tachycardias during Compensated Cardiac Hypertrophy in Rats
Abstract
Background: Ventricular remodeling increases the propensity of ventricular tachyarrhythmias and sudden death in patients. We studied the mechanism underlying these fatal arrhythmias, electrical and structural cardiac remodeling, as well as arrhythmogeneity during early, compensated hypertrophy in a rat model of chronic pressure overload.
Methods: Twenty-six Wistar rats were subjected to transverse aortic constriction (TAC) (n = 13) or sham operation (n = 13). Four weeks postoperative, echo- and electrocardiography was performed. Epicardial (208 or 455 sites) and transmural (30 sites) ventricular activation mapping was performed on Langendorff perfused hearts. Subsequently, hearts were processed for (immuno)histological and molecular analyses.
Results: TAC rats showed significant hypertrophy with preserved left ventricular (LV) function. Epicardial conduction velocity (CV) was similar, but more dispersed in TAC. Transmural CV was slowed in TAC (37.6 ± 2.9 cm s−1 ) compared to sham (58.5 ± 3.9 cm s−1 ; P < 0.01). Sustained polymorphic ventricular tachycardias were induced from LV in 8/13 TAC and in 0/13 sham rats. During VT, electrical activation patterns showed variable sites of earliest epicardial activation and altering sites of functional conduction block. Wandering epicardial reentrant activation was sporadically observed. Collagen deposition was significantly higher in TAC compared to sham, but not different between arrhythmogenic and non-arrhythmogenic TAC animals. Connexin43 (Cx43) expression was heterogeneous with a higher prevalence of non-phosphorylated Cx43 in arrhythmogenic TAC animals.
Conclusion: In TAC rats with compensated cardiac hypertrophy, dispersion of conduction correlated to arrhythmogenesis, an increased heterogeneity of Cx43, and a partial substitution with non-phosphorylated Cx43. These alterations may result in the increased vulnerability to polymorphic VTs.
☑赞☑收藏☑在看☑分享
是对我们的最大支持！