醛固酮促进心房颤动发生研究

The research about aldosterone promotes atrial fibrillation in rats

目的：研究旨在阐明醛固酮独立于负荷的效应对心房结构和电生理的影响。方法在大鼠皮下植入渗透性微泵并以1．5μg/h给醛固酮（ Aldo）。其中未接受醛固酮组作为对照组。8周后,记录活体大鼠体表心电图,心房颤动（房颤）诱发及心房压力。心脏离体测量左心室功能。自心外膜测量左心房（ LA）和右心房（ RA）传导。并测量心房有效不应期（ AERP）。随后对心房进行组织学分析。结果 Aldo大鼠心室收缩、舒张功能及心房压力均未发生改变。所有Aldo组（11只）均可诱发出房性心律失常,而对照组（9只）中仅2只诱发出房性心律失常（P=0.03）。在Aldo组中,P波时限及总的RA激动时间延长,局部传导时间延长,而AERP在两组中差异无统计学意义。在Aldo组中,心房纤维母细胞和间质胶原增加,活化的基质金属蛋白酶-13减少以及心房肌细胞肥大。连接蛋白43未发生改变。结论醛固酮是导致以心房纤维化、心房肌细胞肥大和传导障碍为特点的房性心律失常的基础。在上述模型中心室的血流动力学未发生改变,心房致心律失常归因于醛固酮。这种机制对房颤的一级及二级预防有治疗影响。

Objective The aim of the study was to investigate the effects of aldosterone on atrial struc-ture and electrophysiology. Methods Osmotic mini-pumps delivering 1. 5 μg/h aldosterone were implanted subcutaneously in rats （Aldo）. Rats without aldosterone treatment served as controls. After 8 weeks,surface electrocardiogram, the inducibility of AF, and atrial pressures were recorded in vivo. In isolated working hearts,left ventricular function was measured,and conduction in the right atrium （RA） and the left atrium （LA） was mapped epicardially. The atrial effective refractory period （AERP） was determined. Atrial tissue was analysed histologically. Results systolic and diastolic ventricular function and atrial pressures were not altered in Aldo rats. All Aldo rats（11/11）showed inducible atrial arrhythmias vs. two of nine controls （P=0. 03） . In Aldo,the P-wave duration and the total RA activation time were longer. Prolongation of local con-duction times occurred more often in Aldo,whereas the AERP did not differ between both groups. In Aldo,atri-al fibroblasts and interstitial collagen were increased,active matrix metalloproteinase 13 was reduced,and atrial myocytes were hypertrophied. The connexin43 content was unaltered. Conclusion Aldosterone causes a sub-strate for atrial arrhythmias characterized by atrial fibrosis,myocyte hypertrophy,and conduction disturbances. The described model imputes atrial proarrhythmia directly to aldosterone,since ventricular haemodynamics ap-peared unaltered in this model. This mechanism may have therapeutical impact for primary and secondary pre-vention of AF.