title: Saralasin suppresses arrhythmias in an isolated guinea pig ventricular free wall model of simulated ischemia and reperfusion.
abstract: The effects of saralasin on electrophysiological changes and arrhythmias induced by simulated ischemia and reperfusion were examined in an isolated tissue model. Segments of guinea pig right ventricles, stimulated regularly, were exposed to simulated ischemia for 15 min and then were reperfused with normal Tyrode's solution for 30 min. Transmembrane electrical activity and a high-gain electrogram were recorded. Arrhythmias and electrophysiological changes accompanying simulated ischemia and reperfusion in control preparations were compared to those in preparations treated with 0.1 or 1 microM saralasin. Simulated ischemia caused abbreviation of action potential duration measured at 90% repolarization, abbreviation of endocardial effective refractory period (ERP) and prolongation of transmural conduction time. Premature ventricular beats, ventricular tachycardia and conduction block were observed in approximately 35% of control preparations during simulated ischemia. Rapid sustained or nonsustained ventricular tachycardia occurred in approximately 60% of control preparations in early reperfusion. The overall incidence of arrhythmias and the incidence of ventricular tachycardia in early reperfusion were significantly decreased by 1 microM but not 0.1 microM saralasin. Saralasin (1 microM) prolonged the ERP in normoxic tissues, but it did not alter changes induced by ischemia or reperfusion in ERP or the action potential duration at 90% repolarization. Prolongation of transmural conduction time during ischemia and early reperfusion was significantly inhibited by both concentrations of saralasin. However, only 1 microM saralasin reduced the ratio of transmural conduction time to ERP enough to prevent arrhythmias. Our observations demonstrate that saralasin exerts antiarrhythmic effects in myocardial reperfusion by a mechanism independent of circulatory and central actions.
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: G P
authors.initials: GP
authors.lastname: Thomas
authors.forename: S E
authors.initials: SE
authors.lastname: Howlett
authors.forename: G R
authors.initials: GR
authors.lastname: Ferrier
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000150:complications*; D015425:Myocardial Reperfusion / Q000009:adverse effects; D012504:Saralasin / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D012504:Saralasin