title: Central Sympathetic Activation and Arrhythmogenesis during Acute Myocardial Infarction: Modulating Effects of Endothelin-B Receptors.
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.
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Theofilos M
authors.initials: TM
authors.lastname: Kolettis
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Kontonika
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Barka
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Evangelos P
authors.initials: EP
authors.lastname: Daskalopoulos
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Giannis G
authors.initials: GG
authors.lastname: Baltogiannis
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Tourmousoglou
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece ; Experimental Research Center ELPEN , Athens , Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: Cardiovascular Research Institute , Ioannina and Athens , Greece.
authors.forename: Zenon S
authors.initials: ZS
authors.lastname: Kyriakides
keywords: acute myocardial infarction; endothelin receptors; sympathetic activation; ventricular arrhythmias