Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Nangang District, People's Republic of China.
Basic Res Cardiol. 2011 May;106(3):495-506. doi: 10.1007/s00395-011-0154-3. Epub 2011 Feb 13.
High thoracic epidural anesthesia (HTEA) blocks the afferent and efferent cardiac sympathetic nerve fibers and may affect atrial electrophysiological characteristics and nerve sprouting in patients with atrial fibrillation (AF). In this study, 18 dogs were randomly divided into a control group (n = 6), in which dogs were atrially paced at 400 beats/min for 6 weeks; an HTEA group (n = 6), in which dogs underwent atrial pacing and HTEA for 6 weeks; and a sham-operated group (n = 6), in which dogs underwent the operation but did not receive atrial pacing or HTEA. Electrophysiological examinations were performed in all groups. Cardiac nerves were immunocytochemically stained with anti-growth-associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. The protein expressions of nerve growth factor (NGF), GAP43 and TH in atrial myocardium were also studied by western blot. In addition, the plasma levels of C-reactive protein (CRP) and norepinephrine, as well as atrial production of superoxide anion (O(2)(·-)) and malondialdehyde, were measured. In the HTEA group, atrial effective refractory period increased (P < 0.05) and AF maintenance decreased (P < 0.01) significantly compared with the control group. The densities of GAP43-positive nerves and TH-positive nerves were significantly lower in the HTEA group compared with the control group. The protein levels of NGF, GAP43 and TH were also lower in the HTEA group compared with the control group. A significant positive correlation between the expressions of NGF and GAP43 (P < 0.01) was observed. A similar correlation was demonstrated for NGF and TH (P < 0.01) in our study. Furthermore, the plasma levels of CRP and norepinephrine, as well as the amount of O(2)(·-) and malondialdehyde produced from myocardium, decreased in the HTEA group compared with the control group. In conclusion, HTEA inhibited electrical and nerve remodeling and reduced the maintenance of AF in a canine AF model, in which process HTEA exhibited anti-inflammatory and antioxidant effects, indicating that, in addition to the efferent cardiac sympathetic nerve, afferent fibers also play an important role in the initiation and/or maintenance of AF.
高位胸段硬膜外麻醉(HTEA)阻滞心交感传入和传出神经纤维,可能影响心房颤动(AF)患者的心房电生理特征和神经发芽。在这项研究中,18 只狗被随机分为对照组(n = 6),其中狗以 400 次/分钟的频率进行心房起搏 6 周;HTEA 组(n = 6),其中狗进行心房起搏和 HTEA 6 周;假手术组(n = 6),其中狗接受手术但未进行心房起搏或 HTEA。所有组均进行电生理检查。用抗生长相关蛋白 43(GAP43)和酪氨酸羟化酶(TH)抗体对心脏神经进行免疫细胞化学染色。还通过 Western blot 研究心房心肌中神经生长因子(NGF)、GAP43 和 TH 的蛋白表达。此外,还测量了 C 反应蛋白(CRP)和去甲肾上腺素的血浆水平,以及超氧阴离子(O2(·-))和丙二醛的心房产生。与对照组相比,HTEA 组心房有效不应期延长(P < 0.05),AF 维持减少(P < 0.01)。与对照组相比,HTEA 组 GAP43 阳性神经和 TH 阳性神经的密度显著降低。与对照组相比,HTEA 组 NGF、GAP43 和 TH 的蛋白水平也较低。在我们的研究中,观察到 NGF 和 GAP43 的表达之间存在显著的正相关(P < 0.01)。NGF 和 TH 之间也存在类似的相关性(P < 0.01)。此外,与对照组相比,HTEA 组 CRP 和去甲肾上腺素的血浆水平以及心肌产生的 O2(·-)和丙二醛的量均降低。总之,HTEA 抑制电和神经重塑,并减少犬 AF 模型中 AF 的维持,在此过程中 HTEA 表现出抗炎和抗氧化作用,表明除了传出心交感神经外,传入纤维在 AF 的发生和/或维持中也发挥重要作用。