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Endothelin receptor- : A blockade decreases ventricular arrhythmias after myocardial infarction in rats

Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-1 receptor blockade, examined shortly after MI, have been debated. In the pr...

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Published in:Cardiovascular research 2005-09, Vol.67 (4), p.647-654
Main Authors: BALTOGIANNIS, Giannis G, TSALIKAKIS, Dimitrios G, MITSI, Agathokleia C, HATZISTERGOS, Konstantinos E, ELAIOPOULOS, Dimitrios, FOTIADIS, Dimitrios I, KYRIAKIDES, Zenon S, KOLETTIS, Theofilos M
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Language:English
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Summary:Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-1 receptor blockade, examined shortly after MI, have been debated. In the present study, we examined the effects of such treatment on VT/VF during the first 24 h post-MI. Thirty-five Wistar rats (223+/-22 g) were randomly allocated to either the ET-1 receptor-A (ETA) antagonist BQ-123 (0.4 mg/kg, BQ-123 group, n=17), or normal saline (control group, n=18) and were subjected to coronary artery ligation. A single-lead electrocardiogram was continuously recorded for 24 h post-MI, using an implanted telemetry system, and episodes of VT/VF were analyzed. Monophasic action potential (MAP) recordings were obtained from the left (LV) and right (RV) ventricular epicardium at baseline, 5 min after treatment and 24 h post-MI. There were 15.94+/-19.35 episodes/h/rat of VT/VF in the control group and 1.66+/-2.22 in the BQ-123 group (p=0.010), resulting in a lower (p=0.030) arrhythmic mortality in treated animals. The mean episode duration was 7.40+/-7.16 s for the control group and 2.30+/-1.37 s for the BQ-123 group (p=0.011). The maximum decrease in VT/VF was observed during the 1st, 5th and 6th hours post-MI. In the control group, LV MAP duration increased 24 h post-MI, displaying an increased beat-to-beat variation, but remained unchanged in the BQ-123 group. Acute ETA blockade reduces the incidence of VT/V F during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization.
ISSN:0008-6363
1755-3245
DOI:10.1016/j.cardiores.2005.04.020