Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart.
Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart.
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DOI：
10.1016/j.jacep.2020.09.012
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Efimov IR
中科院分区：
文献类型：
--
作者：
Brennan JA;Chen Q;Gams A;Dyavanapalli J;Mendelowitz D;Peng W;Efimov IR
本研究旨在调查健康和衰竭哺乳动物心脏在整个生理心率 (HR) 范围内主要起搏器位置的变化，并从分子角度表征自发活动的空间区域。正常心跳起源于一组称为窦房结 (SAN) 的起搏细胞的动作电位，该细胞位于上腔静脉附近。众所周知，成人心脏中心率和起搏器活动起源的解剖部位会随着各种生理输入而动态变化，但这种起搏器变化的机制尚不清楚。将光学测绘应用于离体大鼠和人类分离的右心房组织，并用乙酰胆碱和异丙肾上腺素调节 HR。对引发自发活动的组织区域进行 RNA 测序，并与邻近的心肌组织进行比较。功能和分子证据识别并证实了位于上腔静脉和下腔静脉附近的 2 个相互竞争的右心房起搏器的存在，分别是上腔静脉 (sSAN) 和下腔静脉 (iSAN)，它们优先控制快心率和慢心率。这两个区域在未衰竭的大鼠和人类心脏中都很明显，并且当彼此物理分离时，大鼠心脏中仍保持自发活动。对这两个起搏器区域的分子分析揭示了独特但相似的转录谱，表明当 sSAN 沉默时 iSAN 占主导地位。哺乳动物心脏中存在两种空间上不同的主要起搏器（sSAN 和 iSAN），这澄清了先前对哺乳动物物种中迁移起搏器的识别以及 P 波形态的相应变化。
This study sought to investigate the shift of leading pacemaker locations in healthy and failing mammalian hearts over the entire range of physiological heart rates (HRs), and to molecularly characterize spatial regions of spontaneous activity. A normal heartbeat originates as an action potential in a group of pacemaker cells known as the sinoatrial node (SAN), located near the superior vena cava. HRs and the anatomical site of origin of pacemaker activity in the adult heart are known to dynamically change in response to various physiological inputs, yet the mechanism of this pacemaker shift is not well understood. Optical mapping was applied to ex vivo rat and human isolated right atrial tissues, and HRs were modulated with acetylcholine and isoproterenol. RNA sequencing was performed on tissue areas that elicited spontaneous activity, and comparisons were made to neighboring myocardial tissues. Functional and molecular evidence identified and confirmed the presence of 2 competing right atrial pacemakers localized near the superior vena cava and the inferior vena cava—the superior SAN (sSAN) and inferior SAN (iSAN), respectively—which preferentially control the fast and slow HRs. Both of these regions were evident in non-failing rat and human hearts and maintained spontaneous activity in the rat heart when physically separated from one another. Molecular analysis of these 2 pacemaker regions revealed unique but similar transcriptional profiles, suggesting iSAN dominance when the sSAN is silent. The presence of 2 spatially distinct dominant pacemakers, sSAN and iSAN, in the mammalian heart clarifies previous identification of migrating pacemakers and corresponding changes in P-wave morphology in mammalian species.
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影响因子：
37.8
作者：
Park DS;Fishman GI
通讯作者：
Fishman GI
DOI：
10.1152/ajpheart.00756.2009
发表时间：
2010-08-01
影响因子：
4.8
作者：
Glukhov, Alexey V.;Fedorov, Vadim V.;Efimov, Igor R.
通讯作者：
Efimov, Igor R.
影响因子：
--
作者：
BOINEAU, JP;SCHUESSLER, RB;WYLDS, AC
通讯作者：
WYLDS, AC
影响因子：
10.8
作者：
Morris, Gwilym M.;D'Souza, Alicia;Boyett, Mark R.
通讯作者：
Boyett, Mark R.
影响因子：
24
作者：
Fedorov, Vadim V.;Glukhov, Alexey V.;Chang, Roger;Kostecki, Geran;Aferol, Hyuliya;Hucker, William J.;Wuskell, Joseph P.;Loew, Leslie M.;Schuessler, Richard B.;Moazami, Nader;Efimov, Igor R.
通讯作者：
Efimov, Igor R.