Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan City, People's Republic-PR. of China.
PLoS One. 2013 May 27;8(5):e64611. doi: 10.1371/journal.pone.0064611. Print 2013.
We have previously demonstrated that catheter-based renal sympathetic denervation (RSD) could suppress atrial fibrillation (AF) in canines with short-time rapid right atrial pacing (RAP). However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6), the chronic RAP (CRAP) group (n = 7), and the CRAP+RSD group (n = 7). In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05). Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-α and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05). RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05). Picric acid-sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05). Immunohistochemistry results showed that the densities of TH- and GAP43- positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after prolonged RAP in ambulatory canines.
我们之前已经证明，基于导管的肾脏去交感神经（RSD）可以在短时间内通过快速右心房起搏（RAP）抑制犬的心房颤动（AF）。然而，肾脏去神经支配对心房重构的作用尚不清楚。本研究旨在探讨 RSD 对长时间 RAP 期间心房重构的长期影响。20 只杂种犬被植入高频心脏起搏器，通过静脉内导联插入右心房附件。这些狗被分为三组：假手术组（n=6）、慢性 RAP 组（n=7）和 RAP+RSD 组（n=7）。在 RAP+RSD 组中，在双侧 RSD 后 6 周植入起搏器以恢复。RAP 在 RAP+RSD 组和 RAP 组中维持 5 周。与假手术组相比，RAP 组的血浆血管紧张素 II 和醛固酮水平显著升高，但 RAP+RSD 组的升高趋势较 RAP 组有所抑制（P<0.05）。同样，RSD 抑制了 RAP 延长引起的左心房 ANP、TNF-α和 IL-6水平的升高趋势。与假手术组相比，RAP 组的 caspase-3、bax 和 Cx40 水平显著升高，而 Bcl-2 水平降低（P<0.05）。与 RAP 组相比，RSD 明显降低了 caspase-3、bax 和 Cx40 的上调以及 Bcl-2 表达的下调（P<0.05）。苦味酸-天狼星红染色研究表明，RSD 可以显著减轻 RAP 引起的心脏纤维化损伤程度（P<0.05）。免疫组织化学结果显示，RAP 组的 TH-和 GAP43-阳性神经密度明显高于假手术组，而 RSD 手术显著抑制了 RAP 引起的这些变化。这些发现表明，肾脏去神经支配可以抑制慢性 RAP 后犬的心房重构。
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