起搏治疗对心脏自主神经基质改变的实验研究

Cardiac neural substrate changes caused by pacemaker in dog models

目的观察窦房结和房室结功能障碍对心脏神经基质的影响，以及右心耳（RAA）和右心室心尖部（RVA）起搏对神经重构的作用。方法28只犬随机分为窦房结损伤组、RAA起搏组、房室结损伤组和RVA起搏组。7只健康犬作为对照组。14只犬用20％甲醛滤纸片外敷窦房结区损伤窦房结，其中7只犬将起搏电极导线缝合固定于RAA上，以90~．／min行心房起搏。另外14只犬于房室交界区注入无水乙醇损伤房室结，其中7只犬将起搏电极导线缝合固定于RVA，以907~／min起搏心室。起搏60d后二次麻醉，取出心脏。所有犬均于RAA、房间隔（As）、左心耳（LAA）、RVA、室问隔（Vs）、左心室心尖部（LVA）取材。运用免疫组化技术测定心肌中的新生神经（GAP43标测）和交感神经（TH标测）密度。结果（1）窦房结损伤组RAA的新生神经和交感神经密度低于正常对照组（P〈0．01），但AS、LAA及心室的新生神经和交感神经密度与对照组相似（P〉0．05）；（2）RAA起搏组RAA的新生神经与交感性神经密度高于窦房结损伤组（P〈0．01），与对照组接近（P〉0．05）；（3）房室结损伤组心房和心室各部位的新生神经和交感神经密度高于对照组（P〈0．01）；（4）RVA起搏组心房和心室的新生神经和交感神经密度与房室结损伤组差异无统计学意义（P〉0．05）。结论窦房结和房室结功能障碍可造成心脏神经基质的改变。RAA起搏可以逆转窦房结功能低下造成的神经重构，而RVA起搏不能逆转。

Objective To observe the effects of sinoatrial node （SAN） and atrioventricular node （AVN） dysfunction and right atrial appendage （RAA） and right ventrieular apex （RVA） pacing on the cardiac neural substrate remodeling in dog model. Methods Twenty-eight dogs were randomized into SAN damage group, SAN damage with RAA pacing group, AVN damage group and AVN damage with RVA pacing group. Scraps of paper immerged with formalin were applied on the region of SAN in 14 dogs. Electrodes were sewed on the RAA of 7 SAN damaged dogs to deliver atrial pacing at 90 beats per minute. Alcohol was injected into the region of AVN in 14 dogs. Electrodes were sewed on the RVA of 7 AVN damaged dogs to deliver ventricular pacing at 90 beats per minute. After 60 days of pacing, the animals were sacrificed. Tissues of right atrial appendage （RAA）, atrial septam （AS）, left atrial appendage （LAA）, right ventricular apex （RVA）, ventricular sep- tum （VS） , left ventricular apex （LVA） were harvested for immunohistoehemistry study. The density of newly sprouting nerve （GAP43） and sympathetic nerve （TH） were evaluated. Tissues from 7 healthy dogs were used as control. Results （ 1 ） The density GAP43 and TH positive nerve in the RAA of SAV damage group was low- er than that in control dogs（P〈0. O1 ）. The density GAP43 and TH positive nerve in the AS and LAA of SAV damage group was similar to the control group（ P〉O. 05）. （2） The density GAP43 and TH positive nerve in the RAA of RAA pacing group was higher than that in the SAN damage group（P〈0. 01） and was the same as the control group（P〉O. 05）. （3）The density of GAP43 and TH positive nerve in all atrial and ventricular sites was higher than that in the control group（ P〈O. 01 ）. （4）The density GAP43 and TH positive nerve in all atrial and ventrieular sites was the same as that in AVN damage group（P〉0. 05）. Conclusions SAN and AVN damage can lead to the change of cardiac neural substrate. RAA pacing can reserve the neural remodeling resulting from