AUTHOR=Kolettis Theofilos M. , Kontonika Marianthi , Barka Eleonora , Daskalopoulos Evangelos P. , Baltogiannis Giannis G. , Tourmousoglou Christos , Papalois Apostolos , Kyriakides Zenon S. 

TITLE=Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=2

YEAR=2015

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2015.00006

DOI=10.3389/fcvm.2015.00006

ISSN=2297-055X

ABSTRACT=<p>Sympathetic activation during acute myocardial infarction (MI) is an important arrhythmogenic mechanism, but the role of central autonomic inputs and their modulating factors remain unclear. Using the <italic>in vivo</italic> rat-model, we examined the effects of clonidine, a centrally acting sympatholytic agent, in the presence or absence of myocardial endothelin-B (ETB) receptors. We studied wild-type (<italic>n</italic> = 20) and ETB-deficient rats (<italic>n</italic> = 20) after permanent coronary ligation, with or without pretreatment with clonidine. Cardiac rhythm was continuously recorded for 24 h by implantable telemetry devices, coupled by the assessment of autonomic and heart failure indices. Sympathetic activation and arrhythmogenesis were more prominent in ETB-deficient rats during the early phase post-ligation. Clonidine improved these outcomes throughout the observation period in ETB-deficient rats, but only during the delayed phase in wild-type rats. However, this benefit was counterbalanced by atrioventricular conduction abnormalities and by higher incidence of heart failure, the latter particularly evident in ETB-deficient rats. Myocardial ETB-receptors attenuate the arrhythmogenic effects of central sympathetic activation during acute MI. ETB-receptor deficiency potentiates the sympatholytic effects of clonidine and aggravates heart failure. The interaction between endothelin and sympathetic responses during myocardial ischemia/infarction and its impact on arrhythmogenesis and left ventricular dysfunction merits further investigation.</p>