title: Increased monophasic action potential dispersion in endothelin-1-induced ventricular arrhythmias.
abstract: The aim of this study was to investigate the changes in monophasic action potentials (MAP) from different sites in the heart and to determine MAP dispersion during endothelin-1 (ET-1) infusion. Standard ECG, left ventricular anterior, right ventricular lateral, right ventricular septal, and right ventricular apical MAPs and intra-arterial blood pressure were monitored in seven anesthetized open-chest mongrel dogs. After radiofrequency atrioventricular node ablation, ventricular pacing (70/min) was performed and intracoronary ET-1 (60 pmol/min) was administered into the left anterior descending coronary artery. Both MAPd90 and MAPd90 dispersion increased significant during ET-1 infusion. The onset of spontaneous monomorphic and polymorphic sustained ventricular tachycardias (sVT) was observed in five dogs (around 40 min), and nonsustained VTs (nsVT) developed in another two dogs. The increases in MAP and MAP dispersion lasted until the appearance of polymorphic nsVTs and sVTs, but at the time of these VTs this difference decreased. At the termination of the experiments, ventricular fibrillation occurred in six cases. In four cases third-phase early afterdepolarizations were recorded. Our results suggest that increased MAP dispersion and development of EAD contribute to the arrhythmogenic action of ET-1, and these phenomena might explain the pathogenesis of a wide variety of ventricular arrhythmias with different morphology observed in this study.
authors.affiliation: Department of Cardiovascular Surgery, Semmelweis Medical University, Budapest, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Gellér
authors.forename: B
authors.initials: B
authors.lastname: Merkely
authors.forename: V
authors.initials: V
authors.lastname: Lang
authors.forename: T
authors.initials: T
authors.lastname: Szabó
authors.forename: L
authors.initials: L
authors.lastname: Fazekas
authors.forename: V
authors.initials: V
authors.lastname: Kékesi
authors.forename: O
authors.initials: O
authors.lastname: Kiss
authors.forename: F
authors.initials: F
authors.lastname: Horkay
authors.forename: M
authors.initials: M
authors.lastname: Schaldach
authors.forename: M
authors.initials: M
authors.lastname: Tóth
authors.forename: A
authors.initials: A
authors.lastname: Juhász-Nagy
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels; D004285:Dogs; D019332:Endothelin-1 / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D013997:Time Factors
chemical_list: D019332:Endothelin-1