Department of Cardiology, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
ESC Heart Fail. 2022 Dec;9(6):4129-4138. doi: 10.1002/ehf2.14146. Epub 2022 Sep 9.
Our previous study proved that low-level tragus nerve stimulation (LL-TS) could improve left ventricular remodelling by cardiac down-stream mechanisms. However, the cardiac up-stream mechanisms remain unknown.
Twenty-eight adult beagle dogs were randomly divided into an MI group (myocardial infarction was induced by permanent ligation of the left coronary artery, n = 10), an LL-TS group (MI plus intermittent LL-TS treatment, n = 10), and a control group (sham ligation with the same stimulation as the LL-TS group, n = 8). Auricular tragus nerve was bilaterally delivered to the tragus via ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold to set the LL-TS 80% below this level. At the end of 4 weeks post-MI, LL-TS could significantly increase atrial ganglion plex (GP) activity, decreased left stellate ganglion (LSG) activity, reduced LV dilation, and improved ventricular functions. Chronic intermittent LL-TS treatment significantly attenuated left ventricular remodelling via the up-regulation of α7nAChR expression and the down-regulation of MMP-9 level in post-MI LV tissue. The elevated protein and mRNA of MMP-9 levels in remote areas were significantly ameliorated by LL-TS treatment.
Chronic LL-TS increased GP neural activity and improved ventricular remodelling possibly via α7nAChR/MMP-9 axis.
我们之前的研究证明,低位耳轮神经刺激(LL-TS)可以通过心脏下游机制改善左心室重构。然而,心脏上游机制尚不清楚。
28 只成年比格犬随机分为 MI 组(通过永久性结扎左冠状动脉诱导心肌梗死,n=10)、LL-TS 组(MI 加间歇性 LL-TS 治疗,n=10)和对照组(假结扎,给予与 LL-TS 组相同的刺激,n=8)。双侧通过耳夹将耳轮神经传递到耳轮,耳夹连接到定制的刺激器。电压减慢窦率用作阈值,将 LL-TS 设置为低于该水平的 80%。在 MI 后 4 周结束时,LL-TS 可显著增加心房神经节丛(GP)活性,降低左星状神经节(LSG)活性,减少 LV 扩张,并改善心室功能。慢性间歇性 LL-TS 治疗通过上调 MMP-9 水平和下调左室组织中 MMP-9 水平显著减轻左室重构。LL-TS 治疗可显著改善远程区域 MMP-9 水平的升高的蛋白和 mRNA。
慢性 LL-TS 通过α7nAChR/MMP-9 轴增加 GP 神经活性并改善心室重构。