Myocardial Function Section, National Heart and Lung Institute, Imperial College London, Du Cane Road, London W12 0NN, UK.
Department of Cardiology, Hammersmith Hospital, 72 Du Cane Rd, London, W12 0HS, UK.
Europace. 2023 Feb 16;25(2):726-738. doi: 10.1093/europace/euac176.
The response to high frequency stimulation (HFS) is used to locate putative sites of ganglionated plexuses (GPs), which are implicated in triggering atrial fibrillation (AF). To identify topological and immunohistochemical characteristics of presumed GP sites functionally identified by HFS.
Sixty-three atrial sites were tested with HFS in four Langendorff-perfused porcine hearts. A 3.5 mm tip quadripolar ablation catheter was used to stimulate and deliver HFS to the left and right atrial epicardium, within the local atrial refractory period. Tissue samples from sites triggering atrial ectopy/AF (ET) sites and non-ET sites were stained with choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH), for quantification of parasympathetic and sympathetic nerves, respectively. The average cross-sectional area (CSA) of nerves was also calculated. Histomorphometry of six ET sites (9.5%) identified by HFS evoking at least a single atrial ectopic was compared with non-ET sites. All ET sites contained ChAT-immunoreactive (ChAT-IR) and/or TH-immunoreactive nerves (TH-IR). Nerve density was greater in ET sites compared to non-ET sites (nerves/cm2: 162.3 ± 110.9 vs. 69.65 ± 72.48; P = 0.047). Overall, TH-IR nerves had a larger CSA than ChAT-IR nerves (µm2: 11 196 ± 35 141 vs. 2070 ± 5841; P < 0.0001), but in ET sites, TH-IR nerves were smaller than in non-ET sites (µm2: 6021 ± 14 586 vs. 25 254 ± 61 499; P < 0.001).
ET sites identified by HFS contained a higher density of smaller nerves than non-ET sites. The majority of these nerves were within the atrial myocardium. This has important clinical implications for devising an effective therapeutic strategy for targeting autonomic triggers of AF.
高频率刺激（HFS）的反应被用来定位可能的神经节丛（GP）部位，这些部位与触发心房颤动（AF）有关。本研究旨在确定通过 HFS 功能识别的假定 GP 部位的拓扑和免疫组织化学特征。
在 4 个 Langendorff 灌注的猪心内，使用 3.5mm 尖端四极消融导管对 63 个心房部位进行 HFS 刺激和检测，刺激和检测在局部心房不应期内进行。从触发房性异位搏动/心房颤动（ET）部位和非 ET 部位的组织样本中分别用胆碱乙酰转移酶（ChAT）和酪氨酸羟化酶（TH）染色，以分别定量测量副交感神经和交感神经。还计算了神经的平均横截面积（CSA）。通过 HFS 识别出至少一个单心房异位搏动的 6 个 ET 部位（9.5%）的组织形态学与非 ET 部位进行了比较。所有 ET 部位均含有胆碱乙酰转移酶免疫反应性（ChAT-IR）和/或酪氨酸羟化酶免疫反应性神经（TH-IR）。与非 ET 部位相比，ET 部位的神经密度更高（神经/cm2：162.3±110.9 比 69.65±72.48；P=0.047）。总的来说，TH-IR 神经的 CSA 大于 ChAT-IR 神经（µm2：11196±35141 比 2070±5841；P<0.0001），但在 ET 部位，TH-IR 神经小于非 ET 部位（µm2：6021±14586 比 25254±61499；P<0.001）。
通过 HFS 识别的 ET 部位包含比非 ET 部位更高密度的较小神经。这些神经的大多数位于心房心肌内。这对于设计针对 AF 自主神经触发的有效治疗策略具有重要的临床意义。
