Ajijola Olujimi A, Lux Robert L, Khahera Anadjeet, Kwon OhJin, Aliotta Eric, Ennis Daniel B, Fishbein Michael C, Ardell Jeffrey L, Shivkumar Kalyanam
Cardiac Arrhythmia Center, University of California, Los Angeles, California;
Neurocardiology Research Center of Excellence, University of California, Los Angeles, California.
Am J Physiol Heart Circ Physiol. 2017 Mar 1;312(3):H608-H621. doi: 10.1152/ajpheart.00575.2016. Epub 2017 Jan 13.
The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, = 12) or anterior myocardial infarction (MI, = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CV) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, < 0.001) but not transverse CV (CV). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CV nor CV was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, < 0.001, and 423 ± 36 vs. 398 ± 36 ms, = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals ( < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis. This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/.
心脏交感神经支配对正常及慢性梗死心室心肌电活动的影响尚不清楚。对心脏正常的约克夏猪（NL组，n = 12）或前壁心肌梗死猪（MI组，n = 9）在基线状态以及左、右星状神经节刺激（分别为LSGS和RSGS）期间，对左心室心尖前部进行高分辨率标测。测量传导速度（CV）、激动时间（ATs）和激动传播方向。使用扩散张量成像和组织学方法确定心肌纤维方向。RSGS可增加纵向CV（CVl）（0.98±0.11对1.2±0.14m/s，P<0.001），但不增加横向CV（CVt）。β-肾上腺素能受体和缝隙连接（GJ）阻断可消除这种增加。LSGS既不增加CVl也不增加CVt。在梗死周边区域，RSGS和LSGS均可缩短窦性心律时的ARIs（分别为423±37对322±30ms，P<0.001，以及423±36对398±36ms，P = 0.035），并改变所有动物的激动模式。通过平均ATs估算的CVl，RSGS使其以方向依赖性方式增加（14.6±1.2对17.3±1.6ms，P = 0.015），这与GJ侧向化有关。在MI组动物中，RSGS和LSGS分别使75%和67%的标测区域内的AT不均匀调节，并在部分区域诱导相对或绝对功能性激动延迟，而在对照组动物中分别为0%和15%（两者P<0.001）。总之，交感神经兴奋可增加正常心肌的CV，并调节梗死周边心室心肌的激动传播。这些数据表明交感神经对致心律失常的梗死周边基质具有功能控制作用，并部分解释了心律失常发生的时间特性。本研究证明了交感神经对正常心脏传导速度的区域控制。然而，在梗死心脏中，不仅激动传播的调节是异质性的，一些区域还出现了矛盾的传导减慢。交感神经兴奋改变了所有研究的梗死心脏中的激动传播，我们描述了这些发现的致心律失常时间潜力。收听本文对应的播客：http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/ 。
