Anderson Kelley P
Department of Cardiology, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA.
Ann Noninvasive Electrocardiol. 2003 Jan;8(1):75-89. doi: 10.1046/j.1542-474x.2003.08112.x.
Sympathetic nervous system activity (SNSA) is believed to participate in the genesis of ventricular tachyarrhythmias (VTA) but understanding has been impeded by the number and complexity of effects and the paucity of data from humans. New information from studies of genetic disorders, animal models, and spontaneous human arrhythmias indicates the importance of the temporal pattern of SNSA in arrhythmia development. The proarrhythmic effects of short-term elevations of SNSA are exemplified by genetic disorders and include enhancement of early and delayed afterdepolarizations and increased dispersion of repolarization. The role of long-term elevations of SNSA is suggested by animal models of enhanced SNSA signaling that results in apoptosis, hypertrophy, and fibrosis, and sympathetic nerve sprouting caused by infusion of nerve growth factor. Processes that overlap short- and long-term effects are suggested by changes in R-R interval variability (RRV) that precede VTA in patients by several hours. SNSA-mediated alterations in gene expression of ion channels may account for some intermediate-term effects. The propensity for VTA is highest when short-, intermediate, and long-term changes are superimposed. Because the proarrhythmic effects are related to the duration and intensity of SNSA, normal regulatory processes such as parasympathetic activity that inhibits SNSA, and oscillations that continuously vary the intensity of SNSA may provide vital antiarrhythmic protection that is lost in severe heart failure and other disorders. These observations may have therapeutic implications. The recommended use of beta-adrenergic receptor blockers to achieve a constant level of inhibition does not take into account the temporal patterns and regional heterogeneity of SNSA, the proarrhythmic effects of alpha-adrenergic receptor stimulation, or the potential proarrhythmic effects of beta-adrenergic receptor blockade. Further research is needed to determine if other approaches to SNSA modulation can enhance the antiarrhythmic effects.
交感神经系统活动（SNSA）被认为参与了室性快速心律失常（VTA）的发生，但由于其效应的数量和复杂性以及来自人类的数据匮乏，对其的理解受到了阻碍。来自遗传疾病、动物模型和自发性人类心律失常研究的新信息表明，SNSA的时间模式在心律失常发展中具有重要性。SNSA短期升高的促心律失常作用在遗传疾病中得到体现，包括早期和延迟后去极化的增强以及复极离散度的增加。SNSA长期升高的作用通过增强SNSA信号传导的动物模型得以提示，这些模型会导致细胞凋亡、肥大和纤维化，以及由神经生长因子输注引起的交感神经发芽。VTA患者在数小时前R-R间期变异性（RRV）的变化提示了短期和长期效应重叠的过程。SNSA介导的离子通道基因表达改变可能解释了一些中期效应。当短期、中期和长期变化叠加时，发生VTA的倾向最高。由于促心律失常作用与SNSA的持续时间和强度有关，正常的调节过程，如抑制SNSA的副交感神经活动以及不断改变SNSA强度的振荡，可能提供至关重要的抗心律失常保护，而在严重心力衰竭和其他疾病中这种保护会丧失。这些观察结果可能具有治疗意义。推荐使用β-肾上腺素能受体阻滞剂以达到恒定的抑制水平，但并未考虑SNSA的时间模式和区域异质性、α-肾上腺素能受体刺激的促心律失常作用或β-肾上腺素能受体阻滞的潜在促心律失常作用。需要进一步研究以确定其他调节SNSA的方法是否能增强抗心律失常作用。
