Xiong Liang, Liu Yu, Zhou Mingmin, Wang Guangji, Quan Dajun, Shuai Wei, Shen Caijie, Kong Bin, Huang Congxin, Huang He
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Cardiovascular Research Institute of Wuhan University, Wuhan, China.
Exp Physiol. 2018 Sep;103(9):1221-1229. doi: 10.1113/EP086928. Epub 2018 Aug 7.
What is the central question of this study? Can targeted ablation of cardiac sympathetic neurons suppress myocardial infarction-induced adverse cardiac remodelling and left ventricular dysfunction? What is the main finding and its importance? Targeted ablation of cardiac sympathetic neurons significantly alleviated sympathetic remodelling and neuroendocrine activation, attenuated cardiac hypertrophy and fibrosis and improved left ventricular function. Thus, targeted ablation of cardiac sympathetic neurons might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction.
Sympathetic overactivation is crucial in the development and progression of adverse cardiac remodelling and dysfunction. Targeted ablation of cardiac sympathetic neurons (TACSN) is an effective approach to inhibit overactivation of the sympathetic nervous system. The aim of this study was to investigate whether TACSN could suppress myocardial infarction (MI)-induced adverse cardiac remodelling and dysfunction, thereby producing protective effects. Thirty-eight dogs were randomly assigned into the sham-operated, MI or MI-TACSN group. The TACSN was induced by injecting cholera toxin B subunit-saporin compound into the stellate ganglia 1 week after MI. Five weeks after MI surgery, echocardiographic and haemodynamic parameters of cardiac function were significantly improved in the TACSN group compared with the MI group. In addition, TACSN attenuated the extent of cardiac hypertrophy and fibrosis and suppressed the increase in the plasma concentrations of noradrenaline, nerve growth factor, atrial natriuretic peptide, brain natriuretic peptide, angiotensin II and aldosterone. Furthermore, TACSN alleviated the growth associated protein-43-positive and tyrosine hydroxylase-positive nerve densities in the infarcted border zone and restored protein expression of the β -adrenergic receptor in the left ventricular myocardium. These findings indicate that TACSN might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction, which might be attributable, at least in part, to the attenuation of both sympathetic remodelling and the cardiac neuroendocrine system.
本研究的核心问题是什么？心脏交感神经元的靶向消融能否抑制心肌梗死诱导的不良心脏重塑和左心室功能障碍？主要发现及其重要性是什么？心脏交感神经元的靶向消融显著减轻了交感神经重塑和神经内分泌激活，减轻了心肌肥大和纤维化，并改善了左心室功能。因此，心脏交感神经元的靶向消融可能对梗死后不良重塑和左心室功能障碍具有有益作用。
交感神经过度激活在不良心脏重塑和功能障碍的发生发展中起关键作用。心脏交感神经元的靶向消融（TACSN）是抑制交感神经系统过度激活的有效方法。本研究的目的是探讨TACSN是否能抑制心肌梗死（MI）诱导的不良心脏重塑和功能障碍，从而产生保护作用。38只犬被随机分为假手术组、MI组或MI-TACSN组。MI后1周，通过向星状神经节注射霍乱毒素B亚基-皂草素复合物诱导TACSN。MI手术后5周，与MI组相比，TACSN组的心脏功能超声心动图和血流动力学参数显著改善。此外，TACSN减轻了心肌肥大和纤维化的程度，并抑制了去甲肾上腺素、神经生长因子、心房利钠肽、脑利钠肽、血管紧张素II和醛固酮血浆浓度的升高。此外，TACSN减轻了梗死边缘区生长相关蛋白43阳性和酪氨酸羟化酶阳性神经密度，并恢复了左心室心肌中β-肾上腺素能受体的蛋白表达。这些发现表明，TACSN可能对梗死后不良重塑和左心室功能障碍具有有益作用，这可能至少部分归因于交感神经重塑和心脏神经内分泌系统的减弱。
