Abstract
The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-α, IL-1β, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on α7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment.
Highlights
Viral myocarditis is an inflammatory disease involving myocardial cells and the myocardial interstitium
We have found that excessive sympathetic activation promotes inflammatory immune responses and aggravates inflammatory lesion in viral myocarditis, and the nonselective β-blocker carvedilol was beneficial due to its effects to limit the production of pro-inflammatory cytokines (Li et al, 2008, 2010, 2012a,b; Zheng et al, 2016)
These findings suggest that the autonomic nervous system can modulate the immune response and regulate inflammation, and the autonomic nervous system dysfunction may play an important role in viral myocarditis (Li, 2016; Zheng et al, 2016)
Summary
Viral myocarditis is an inflammatory disease involving myocardial cells and the myocardial interstitium. The clinical manifestations of viral myocarditis vary; mild cases may have symptoms such as palpitations and fatigue, while severe cases may involve cardiogenic shock, syncope and even sudden death. The majority of viral myocarditis cases recover after treatment, Cervical Vagotomy Aggravates Viral Myocarditis while a few patients eventually develop dilated cardiomyopathy due to ongoing injury with persistent viral infection or immune response (Cooper, 2009). The incidence of viral myocarditis in adults and adolescents increases year by year (Cooper, 2009). Coxsackie virus and other picornaviruses lead to more than 50% of cases of acute myocarditis and approximately 25% of cases of dilated cardiomyopathy. Epidemiological data shows that myocarditis is the main cause of heart failure in patients less than 40 years of age (Yajima and Knowlton, 2009)
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