快速起搏犬左心耳致自主神经功能改变和神经重构的研究

Changes of autonomic nervous function and remodding in rapid left atrial appendage pacing-in- duced canines chronic atrial fibrillation

目的观察快速起搏（RAP）犬左心耳对自主神经功能及神经密度的影响，探讨自主神经系统（ANS）在心房颤动（AF）发生和维持中的作用。方法成年健康Beagle犬14条，体质量（8．674-0．75）kg，雌雄不拘。随机分为快速起搏组（RAP组，n=7）和对照组（CTL组，n=7）。RAP组犬以400次／min连续起搏8周，诱导AF，CTL组不起搏。起搏8周后，应用短程心率变异指标观察犬自主神经功能变化；并用免疫组织化学染色技术检测犬心脏神经生长相关蛋白（GAP-43）、酪氨酸羟化酶（TH）的表达。结果心率变异分析显示RAP组心率变异性（HRV）时域指标均较CTL组降低，频域指标RAP组的低频功率（LF）、高频功率（HF）较CTL组明显降低，LF／HF较CTL组明显增高；免疫组织化学结果显示，与CTL组比较，RAP组犬左心耳可见GAP-43、TH的阳性表达，其神经密度与CTL组比较显著升高；显微镜下显示取样部位心脏神经呈不均一性分布。结论长期快速起搏左心耳致犬的慢性房颤模型中心脏自主神经功能失衡，神经纤维分布及密度改变，引起神经重构导致AF的发生和维持。

Objective To investigate changes of autonomic nervous function and remodeling of au- tonomic nerves in rapid left atrial appendage pacing （RAP）-induced canines chronic atrial fibrillation. Methods Fourteen Beagle dogs were randomly divided into 2 groups： control group （a = 7） and RAP group （n-7 ）. High frequency pacing （400 beats/min） with a permanent pacemaker was given to the RAP group but not to the control group. HRV was performed on all the Beagle dogs. Left atrial appendage samples were obtained and the experssion of tyrosine hydroxylase （TH） and growth associated protein 43 （GAP-43） was detected by using immunocytochemical staining technique. Result The overall frequency of abnormal autonomic nervous function in RAP group ： Data of SDNN （index of sympathetic and pneumogastric con-tonicity） ,RMSSD and PNNS0 （indexes of pneumogastric tonicity） decreased by rapid pacing. All the RAP groups were lower than a normal control group in time domain indexes. The density of TH and GAP-43 positive nerve fibers were significantly higher in RAP groups than CTL groups. Conclusion RAP induces cardiac nerve regenerating and remodeling. These changes could maintain developing of atrial fibrillation.