Abstract：
BACKGROUND: The significance of autonomic dysfunction in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown.
OBJECTIVE: Utilizing a novel \"dual stressor\" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model.
METHODS: In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling.
RESULTS: Exercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload.
CONCLUSIONS: Sympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.
OBJECTIVE: Utilizing a novel \"dual stressor\" provocative challenge combining exercise with premature ventricular contraction (PVCs), the authors characterized the functional and molecular mechanisms of cardiac autonomic (cardiac autonomic nervous system) remodeling in a PVC-CM animal model.
METHODS: In 15 canines (8 experimental, 7 sham), we implanted pacemakers and neurotelemetry devices and subjected animals to 12 weeks of bigeminal PVCs to induce PVC-CM. Sympathetic nerve activity (SNA), vagal nerve activity (VNA), and heart rate were continuously recorded before, during, and after treadmill exercise challenge with and without PVCs, at baseline and after development of PVC-CM. Western blot and enzyme-linked immunosorbent assay were used to evaluate molecular markers of neural remodeling.
RESULTS: Exercise triggered an increase in both SNA and VNA followed by late VNA withdrawal. With PVCs, the degree of exercise-induced SNA augmentation was magnified, whereas late VNA withdrawal became blunted. After PVC-CM development, SNA was increased at rest but failed to adequately augment during exercise, especially with PVCs, coupled with impaired VNA and heart rate recovery after exercise. In the remodeled cardiac autonomic nervous system, there was widespread sympathetic hyperinnervation and elevated transcardiac norepinephrine levels but unchanged parasympathetic innervation, indicating sympathetic overload. However, cardiac nerve growth factor was paradoxically downregulated, suggesting an antineurotrophic counteradaptive response to PVC-triggered sympathetic overload.
CONCLUSIONS: Sympathetic overload, sympathetic dysfunction, and parasympathetic dysfunction in PVC-CM are unmasked by combined exercise and PVC challenge. Reduced cardiac neurotrophic factor might underlie the mechanisms of this dysfunction. Neuromodulation therapies to restore autonomic function could constitute a novel therapeutic approach for PVC-CM.
摘要：
背景：自主神经功能障碍在室性早搏诱导的心肌病（PVC-CM）中的意义尚不清楚。
目的：利用一种新颖的“双重压力源”挑衅性挑战，将运动与室性早搏（PVC）结合起来，作者在PVC-CM动物模型中描述了心脏自主神经（心脏自主神经系统）重塑的功能和分子机制。
方法：在15只犬中（8只实验性，7假)，我们植入起搏器和神经测量装置，并对动物进行12周的双峰PVC诱导PVC-CM。交感神经活动（SNA），迷走神经活动（VNA），之前连续记录心率，during,在有和没有PVC的跑步机运动挑战之后，在基线和PVC-CM开发后。Westernblot和酶联免疫吸附试验用于评估神经重塑的分子标志物。
结果：运动引发了SNA和VNA的增加，随后是晚期VNA退出。有了PVC,运动诱导的SNA增强程度被放大，而晚期VNA退出变得迟钝。PVC-CM发展后,SNA在休息时增加，但在运动期间未能充分增加，尤其是PVC，再加上运动后VNA受损和心率恢复。在重塑的心脏自主神经系统中，存在广泛的交感神经支配过度和心脏去甲肾上腺素水平升高，但副交感神经支配未改变。表明交感神经过载。然而,心脏神经生长因子被矛盾地下调，提示对PVC触发的交感神经过载的抗神经营养反适应性反应。
结论：交感神经超负荷，交感神经功能障碍,PVC-CM中的副交感神经功能障碍被运动和PVC挑战相结合所掩盖。心脏神经营养因子的减少可能是这种功能障碍的机制的基础。恢复自主神经功能的神经调节疗法可以构成PVC-CM的新治疗方法。
目的：利用一种新颖的“双重压力源”挑衅性挑战，将运动与室性早搏（PVC）结合起来，作者在PVC-CM动物模型中描述了心脏自主神经（心脏自主神经系统）重塑的功能和分子机制。
方法：在15只犬中（8只实验性，7假)，我们植入起搏器和神经测量装置，并对动物进行12周的双峰PVC诱导PVC-CM。交感神经活动（SNA），迷走神经活动（VNA），之前连续记录心率，during,在有和没有PVC的跑步机运动挑战之后，在基线和PVC-CM开发后。Westernblot和酶联免疫吸附试验用于评估神经重塑的分子标志物。
结果：运动引发了SNA和VNA的增加，随后是晚期VNA退出。有了PVC,运动诱导的SNA增强程度被放大，而晚期VNA退出变得迟钝。PVC-CM发展后,SNA在休息时增加，但在运动期间未能充分增加，尤其是PVC，再加上运动后VNA受损和心率恢复。在重塑的心脏自主神经系统中，存在广泛的交感神经支配过度和心脏去甲肾上腺素水平升高，但副交感神经支配未改变。表明交感神经过载。然而,心脏神经生长因子被矛盾地下调，提示对PVC触发的交感神经过载的抗神经营养反适应性反应。
结论：交感神经超负荷，交感神经功能障碍,PVC-CM中的副交感神经功能障碍被运动和PVC挑战相结合所掩盖。心脏神经营养因子的减少可能是这种功能障碍的机制的基础。恢复自主神经功能的神经调节疗法可以构成PVC-CM的新治疗方法。
