@ARTICLE{10.3389/fcvm.2015.00006, AUTHOR={Kolettis, Theofilos M. and Kontonika, Marianthi and Barka, Eleonora and Daskalopoulos, Evangelos P. and Baltogiannis, Giannis G. and Tourmousoglou, Christos and Papalois, Apostolos and 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/articles/10.3389/fcvm.2015.00006}, DOI={10.3389/fcvm.2015.00006}, ISSN={2297-055X}, ABSTRACT={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 in vivo 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 (n = 20) and ETB-deficient rats (n = 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.} }