Alteration of Cholinergic Anti-Inflammatory Pathway in Rat With Ischemic Cardiomyopathy-Modified Electrophysiological Function of Heart.
J Am Heart Assoc
; 6(9)2017 Sep 19.
Article
em En
| MEDLINE
| ID: mdl-28928157
ABSTRACT
BACKGROUND:
With chronic ischemia after myocardial infarction, the resulting scar tissue result in electrical and structural remodeling vulnerable to an arrhythmogenic substrate. The cholinergic anti-inflammatory pathway elicited by vagal nerve via α7 nicotinic acetylcholine receptors (α7-nAChR) can modulate local and systemic inflammatory responses. Here, we aimed to clarify a novel mechanism for the antiarrhythmogenic properties of vagal nerve during the ischemic cardiomyopathy (ICM). METHODS ANDRESULTS:
Left anterior descending artery of adult male Sprague-Dawley rats was ligated for 4 weeks to develop ICM. Western blot revealed that eliciting the cholinergic anti-inflammatory pathway by nicotine treatment showed a significant reduction in the amounts of collagens, cytokines, and other inflammatory mediators in the left ventricular infarcted border zone via inhibited NF-κB activation, whereas it increased the phosphorylated connexin 43. Vagotomy inhibited the anti-inflammatory, anti-fibrosis, and anti-arrhythmogenic effect of nicotine administration. And immunohistochemistry confirmed that the nicotine administration-induced increase of connexin 43 was located in intercellular junctions. Furthermore nicotine treatment suppressed NF-κB activation in lipopolysaccharide-stimulated RAW264.7 cells, and α-bungarotoxin (an α7-nAChR selective antagonist) partly inhibited the nicotine-treatment effect. In addition, 4-week nicotine administration slightly improved the cardiac function, increased cardiac parasympathetic tone, decreased the prolonged QTc, and decreased the arrhythmia score of programmed electric stimulation-induced ventricular arrhythmia.CONCLUSIONS:
Eliciting the cholinergic anti-inflammatory pathway exerts anti-arrhythmogenic effects against ICM-induced ventricular arrhythmia accompanied by downregulation of cytokines, downgenerating of collagens, decrease in sympathetic/parasympathetic ratio, and prevention of the loss of phosphorylated connexin 43 during ICM. Our findings may suggest a promising therapy for the generation of ICM-induced ventricular arrhythmia by eliciting the cholinergic anti-inflammatory pathway.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Função Ventricular
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Isquemia Miocárdica
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Colinérgicos
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Técnicas Eletrofisiológicas Cardíacas
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Ventrículos do Coração
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Anti-Inflamatórios
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Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Am Heart Assoc
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China