Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract.
Electrophysiology and Arrhythmogenesis in the Human Right Ventricular Outflow Tract.
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DOI：
10.1161/circep.121.010630
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发表时间：
2022-03
影响因子：
8.4
通讯作者：
Efimov, Igor R.
中科院分区：
文献类型：
--
作者：
Aras, Kedar;Gams, Anna;Faye, Ndeye Rokhaya;Brennan, Jaclyn;Goldrick, Katherine;Li, Jinghua;Zhong, Yishan;Chiang, Chia-Han;Smith, Elizabeth H.;Poston, Megan D.;Chivers, Jacqueline;Hanna, Peter;Mori, Shumpei;Ajijola, Olujimi A.;Shivkumar, Kalyanam;Hoover, Donald B.;Viventi, Jonathan;Rogers, John A.;Bernus, Olivier;Efimov, Igor R.
右心室出口（RVOT）是心脏心动过速的常见来源，这通常需要消融，但是，由于缺乏详细的电力生理学和人类RVOT的分子研究，RVOT独特的心律失常易感性的理解仍然很差。
我们对经过药物诱导的肾上腺素和胆碱能刺激的16种非供体供体的人类RVOT制剂进行了光学映射研究，以评估心律不齐的易感性并表征心律失常动力学。
我们发现，在控制条件下，RVOT相对于右心顶区域（RVAR）具有较短的作用势持续时间（APD80）。 ，而仅乙酰胆碱（100μm）刺激对APD80或PVC没有影响。 PVC（p = 0.034）和部分逆转APD80缩短（p = 0.029）。对透壁心律失常动力学的研究表明，心律不齐波前和相位奇异性（转子）相对有组织。心脏心脏中的心内膜（p = 0.006）。和CGMP-PKG信号传导是可能富含雄性RVOT的途径之一，而神经变性的途径可以富含雌性rvot。
人RVOT电生理学的特征是相对于RVAR的作用较短。心内心律失常的波前和转子相对有组织。
Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT’s unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. We conducted optical mapping studies in 16 non-diseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. We found that under control conditions, RVOT has shorter action potential duration (APD80) relative to the right ventricular apical region (RVAR). Treatment with isoproterenol (100nM) shortened APD80 and increased incidence of premature ventricular contractions (PVCs) (p=0.003), whereas acetylcholine (100μM) stimulation alone had no effect on APD80 or PVCs. However, acetylcholine treatment after isoproterenol stimulation, reduced the incidence of PVCs (p=0.034) and partially reversed APD80 shortening (p=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker vesicular acetylcholine transporter in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wavefronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (p=0.006). Moreover, there was a weak but positive spatio-temporal autocorrelation between epicardial and endocardial arrhythmic wavefronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK signaling, calcium signaling, and cGMP-PKG signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. Human RVOT electrophysiology is characterized by shorter action potential duration relative to the RVAR. Cholinergic RV stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of PVCs and shortening of wavelength. RV arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wavefronts and rotors that are relatively more organized in the endocardium.