犬肾去交感神经对长期快速心房起搏后心房基质和心房颤动诱发的影响

Effect of renal sympathetic denervation on the atrial substrate and inducibility of atrial fibrillation in ambulatory canines of prolonged atrial pacing

目的探讨犬肾去交感神经对长期快速右房起搏后心房基质和心房颤动(AF)诱发的影响。方法 20只犬分为假手术组(n=6)、右房起搏(RAP)组(n=7)和肾去交感神经(RSD)组(n=7)三组。假手术组植入起搏器后程控关闭起搏器;RSD组先行双侧肾交感神经消融,经6周恢复后植入起搏器;RAP组和RSD组快速起搏(400～450次/分)右房5周。所有犬在试验开始时和终点进行血压测量及电生理检测;处死动物后迅速取左房组织,检测组织心房利钠肽(ANP)、血管紧张素Ⅱ(AngⅡ)和醛固酮水平,及组织半胱天冬酶-3(Caspase-3)、Bax、B淋巴细胞瘤-2基因(Bcl-2)、金属蛋白酶组织抑制剂-1(TIMP-1)、基质金属蛋白酶-9(MMP-9)和转化生长因子-β1(TGF-β1)等蛋白表达。结果 RSD组犬肾动脉消融6周后(植入起搏器前)收缩压较消融前显著降低(P=0.001);右房起搏5周后RSD组和RAP组的收缩压和舒张压较假手术组均明显降低(P<0.05),且RSD组收缩压较RAP组更低(P=0.036)。与假手术组和RSD组相比,RAP组起搏5周后诱发的AF持续时间明显延长(P<0.05)。RAP组心房有效不应期(AERP)明显缩短(P=0.002),而RSD组AERP的缩短无显著性(P=0.087)。与假手术组比较,RAP组犬左房的ANP、AngⅡ和醛固酮水平显著升高,而在RSD组其升高的趋势明显减缓(P<0.05)。与RAP组相比,RSD组犬左房的Caspase-3、Bax、MMP-9和TGF-β1蛋白表达显著降低,而Bcl-2和TIMP-1蛋白表达显著升高。结论肾去交感神经可抑制长期快速右房起搏后AF的诱发和心房基质改变。

Objective To investigate the effect of renal sympathetic denervation （RSD）on the atrial substrate and in- ducibility of atrial fibrillation （AF） after prolonged atrial pacing in ambulatory canines. Methods Twenty dogs were im- planted with a high frequency cardiac pacemaker, and were divided into three groups： sham-operated group （n = 6）, right atrial pacing（RAP） group （n=7） and RSD group （n= 7）. Sham-operated group dogs were only implanted with pacemak- ers without pacing. In RSD group dogs, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recov- ery. Atrial pacing was maintained for 5 weeks in both RAP group and RSD group. Electrophysiological test was measured in all the animals at the baseline and endpoint of the protocol. Then the heart was quickly excised and tissue specimens were obtained from the left atrium. The tissue levels of ANP, angiotensin 11 and aldosterone were examined by ELISA, and the exnression levels of Caspase-3. Bax, Bcl-2, TIMP-1, MMP-9 and TGF-131 were examined by western blotting. ResultsSystolic blood pressure was significantly decreased after RSD for 6 weeks in RSD group （P=0. 001 ）. Similarly, systolic blood pressure was decreased after RAP for a mean of 5 weeks in the RAP group and the RSD group （P〈0. 05）. Compared with the sham-operated group and RSD group, RAP group dogs had longer duration of AF induced by SI S1 programmed stimulation after 5 week atrial pacing（P〈0. 05 ）. AERP was significantly shortened after prolonged atrial pacing from 142±8 ms to 115±9 ms in RAP group （P =0.002）. However, the probability value that AERP decreased from 140±10 ms to 127±11ms in RSD group was not sig- nificantly different （ P = 0. 087）. The tissue levels of ANP, angiotensin 11 and aldosterone increased significantly in RAP group, but the increasing trend was significantly inhibited in RSD group （ P〈0. 05）. The expression levels of Caspase-3, Bax, MMP-9 and TGF-[31 in atrial tissue were significantly decreased, while the expression levels of Bcl-2 and TIMP-1 were increased in RSD group than that of RAP group （P〈0. 05）. Conclusion Catheter-based renal denervation can re- duce the inducibility of AF and suppress atrial substrate by prolonged RAP.