title: Endothelin receptor--a blockade decreases ventricular arrhythmias after myocardial infarction in rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, University of Ioannina, 1 University Avenue, 45110 Ioannina, Greece.
authors.forename: Giannis G
authors.initials: GG
authors.lastname: Baltogiannis
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Tsalikakis
authors.forename: Agathokleia C
authors.initials: AC
authors.lastname: Mitsi
authors.forename: Konstantinos E
authors.initials: KE
authors.lastname: Hatzistergos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Elaiopoulos
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Fotiadis
authors.forename: Zenon S
authors.initials: ZS
authors.lastname: Kyriakides
authors.forename: Theofilos M
authors.initials: TM
authors.lastname: Kolettis
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015716:Electrocardiography, Ambulatory; D065130:Endothelin A Receptor Antagonists; D005260:Female; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000503:physiopathology; D013686:Telemetry / Q000379:methods; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)