Khaky Artin, Yang Nicole Lee, van Weperen Valerie, Avasthi Shail, Jani Neil, Vaseghi Marmar
UCLA Cardiac Electrophysiology Programs, Division of Cardiology, Department of Medicine, University of California, Los Angeles, 100 Medical Plaza, Suite 660, Los Angeles, CA 90095, USA.
Biomedicines. 2025 Aug 31;13(9):2126. doi: 10.3390/biomedicines13092126.
A combination of sympathoexcitation and parasympathetic withdrawal contributes to the occurrence of ventricular arrhythmias, sudden cardiac death, and progression of heart failure after myocardial injury. As a result, vagal nerve stimulation has been under investigation as a potential option to increase cardiac vagal tone, but the results of clinical trials have been mixed. Prior studies have suggested that the vagal ganglia and nerves may contain sympathetic neurons that express tyrosine hydroxylase (TH), which, if stimulated, could potentially mitigate the effects of vagal nerve stimulation. The goal of the current study was to better characterize these neurons. Immunohistochemical staining was performed to evaluate for the presence of TH-expressing neurons in the inferior vagal (nodose) ganglia from six pigs. Additional staining was performed for dopamine beta-hydroxylase (DBH), which is required for the production of norepinephrine (NE), to determine if these neurons are indeed sympathetic and capable of releasing NE. Analysis of stellate ganglia was also performed, given that these ganglia are known to provide sympathetic innervation to the heart and release NE in the myocardium. While nearly all TH-expressing neurons in the stellate ganglia expressed DBH, confirming that they can produce or release NE, none of the TH-expressing neurons in the vagal ganglia expressed DBH, demonstrating that these are dopaminergic but not noradrenergic neurons. TH-expressing neurons in the vagal ganglia previously reported to be potentially "sympathetic" do not express DBH and are, therefore, not capable of synthesizing NE.
交感神经兴奋和副交感神经活动减弱共同导致心肌损伤后室性心律失常、心源性猝死及心力衰竭进展。因此，迷走神经刺激作为一种增加心脏迷走神经张力的潜在方法，一直在研究中，但临床试验结果不一。先前的研究表明，迷走神经节和神经可能含有表达酪氨酸羟化酶（TH）的交感神经元，如果受到刺激，可能会减轻迷走神经刺激的影响。本研究的目的是更好地表征这些神经元。对6头猪的迷走神经（结状）下神经节进行免疫组织化学染色，以评估表达TH的神经元的存在情况。对多巴胺β羟化酶（DBH）进行额外染色，该酶是去甲肾上腺素（NE）生成所必需的，以确定这些神经元是否确实是交感神经元且能够释放NE。鉴于星状神经节已知为心脏提供交感神经支配并在心肌中释放NE，因此也对其进行了分析。虽然星状神经节中几乎所有表达TH的神经元都表达DBH，证实它们可以产生或释放NE，但迷走神经节中表达TH的神经元均未表达DBH，表明这些是多巴胺能神经元而非去甲肾上腺素能神经元。迷走神经节中先前报道的可能“交感”的表达TH的神经元不表达DBH，因此不能合成NE。
