Right Atrial Mechanisms of Atrial Fibrillation in a Rat Model of Right Heart Disease
Right Atrial Mechanisms of Atrial Fibrillation in a Rat Model of Right Heart Disease
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DOI：
10.1016/j.jacc.2019.06.066
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发表时间：
2019-09-10
影响因子：
24
通讯作者：
Nattel, Stanley
中科院分区：
文献类型：
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作者：
Hiram, Roddy;Naud, Patrice;Nattel, Stanley
背景影响右心的疾病，包括肺部和肺循环的疾病，促进心房颤动（AF），但其机制知之甚少。方法雄性Wistar大鼠腹腔注射野百合碱60 mg/kg，21天后，当右心疾病发展良好时，对大鼠进行了研究。AF的脆弱性进行了评估，在体内和原位，和机制被定义为光学映射，组织化学，和biochemical.Results野百合碱治疗的大鼠右心室压力和质量增加，沿着与右心房（RA）扩大。32/32只PH大鼠体内（100%）和12/11只原位（92%）可诱导AF/扑动，而对照组大鼠分别为2/32（6%）和2/12（17%）（p < 0.001 vs. PH）。PH大鼠具有显著的RA（16.1 +/- 0.5%横截面积，对照组为3.0 +/- 0.6%）和左心房（LA：11.8 +/- 0.5% vs. 5.4 +/- 0.8%对照）纤维化。多种细胞外基质蛋白，包括胶原1和3，纤维连接蛋白，基质金属蛋白酶2和9，在PH大鼠RA中上调。光学映射显示显着的速率依赖性RA传导减慢和转子活动，包括稳定的转子在4 11 PH大鼠，而没有显着的传导减慢或转子活动发生在LA的野百合碱治疗的大鼠。转录组学分析显示，与对照组相比，野百合碱治疗组大鼠RA中与肥大、炎症和纤维化相关的差异富集基因。PH大鼠的生化结果进行了比较与AF-倾向大鼠心房重构的背景下，左心室功能障碍，由于心肌梗死：心肌梗死大鼠LA共享分子图案与PH大鼠RA。结论右心疾病产生的AF维护由于RA折返活动的基板，与潜在的基板显着涉及RA纤维化和传导异常。(C)2019年由美国心脏病学会基金会。
BACKGROUND Conditions affecting the right heart, including diseases of the lungs and pulmonary circulation, promote atrial fibrillation (AF), but the mechanisms are poorly understood.OBJECTIVES This study sought to determine whether right heart disease promotes atrial arrhythmogenesis in a rat model of pulmonary hypertension (PH) and, if so, to define the underlying mechanisms.METHODS PH was induced in male Wistar rats with a single intraperitoneal injection of 60 mg/kg of monocrotaline, and rats were studied 21 days later when right heart disease was well developed. AF vulnerability was assessed in vivo and in situ, and mechanisms were defined by optical mapping, histochemistry, and biochemistry.RESULTS Monocrotaline-treated rats developed increased right ventricular pressure and mass, along with right atrial (RA) enlargement. AF/flutter was inducible in 32 of 32 PH rats (100%) in vivo and 11 of 12 (92%) in situ, versus 2 of 32 (6%) and 2 of 12 (17%), respectively, in control rats (p < 0.001 vs. PH for each). PH rats had significant RA (16.1 +/- 0.5% of cross-sectional area, vs. 3.0 +/- 0.6% in control) and left atrial (LA: 11.8 +/- 0.5% vs. 5.4 +/- 0.8% control) fibrosis. Multiple extracellular matrix proteins, including collagen 1 and 3, fibronectin, and matrix metalloproteinases 2 and 9, were up-regulated in PH rat RA. Optical mapping revealed significant rate-dependent RA conduction slowing and rotor activity, including stable rotors in 4 of 11 PH rats, whereas no significant conduction slowing or rotor activity occurred in the LA of monocrotaline-treated rats. Transcriptomic analysis revealed differentially enriched genes related to hypertrophy, inflammation, and fibrosis in RA of monocrotaline-treated rats versus control. Biochemical results in PH rats were compared with those of AF-prone rats with atrial remodeling in the context of left ventricular dysfunction due to myocardial infarction: myocardial infarction rat LA shared molecular motifs with PH rat RA.CONCLUSIONS Right heart disease produces a substrate for AF maintenance due to RA re-entrant activity, with an underlying substrate prominently involving RA fibrosis and conduction abnormalities. (C) 2019 by the American College of Cardiology Foundation.