Targeted ablation of cardiac sympathetic neurons attenuates adverse postinfarction remodelling and left ventricular dysfunction.
NEW FINDINGS
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.


ABSTRACT
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 β1 -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.
['Xiong|Liang|L|', 'Liu|Yu|Y|', 'Zhou|Mingmin|M|', 'Wang|Guangji|G|', 'Quan|Dajun|D|', 'Shuai|Wei|W|', 'Shen|Caijie|C|', 'Kong|Bin|B|', 'Huang|Congxin|C|', 'Huang|He|H|0000-0003-3915-2733']
D055011:Ablation Techniques D000818:Animals D002772:Cholera Toxin D004285:Dogs D004452:Echocardiography D015870:Gene Expression D006321:Heart D007267:Injections D008297:Male D009203:Myocardial Infarction D009474:Neurons D009490:Neurosecretory Systems D000076985:Saporins D013233:Stellate Ganglion D013564:Sympathetic Nervous System D018487:Ventricular Dysfunction, Left D020257:Ventricular Remodeling
cardiac sympathetic neurons cardiac remodelling sympathetic remodelling myocardial infarction heart failure