title: I(Ks)  blockade in border zone arrhythmias from guinea-pig ventricular myocardium submitted to simulated ischemia and reperfusion.
abstract: I(Ks) blockade might be a promising way to treat tachyarrhythmia because of the accumulation of activated potassium channels. However, I(Ks) blockade during ischemia/reperfusion has not been investigated. Thus, the electrophysiological effects of two I(Ks) blockers, chromanol 293B (10 μm) and HMR 1556 (1 μm), were assessed in an in vitro model of border zone between normal and ischemic/reperfused right ventricular myocardium from guinea-pigs, and classic electrophysiological parameters and the incidence of arrhythmias were studied. HMR 1556 and chromanol 293B exhibited slight conventional class III effects on action potential duration in the normal zone (NZ) (APD(90) : -2 ± 5%, not significant (NS); +6 ± 3%, NS; and +5 ± 1%, P < 0.05, respectively, in control, HMR 1556, and chromanol 293B groups) but failed to oppose its decrease after 30 min of simulated ischemic superfusion (APD(90) : -52 ± 5%, P < 0.01; -64 ± 5%, P < 0.01; and -61 ± 3%, P < 0.01, respectively, in control, HMR 1556, and chromanol 293B groups), leading to repolarization dispersion between normal and ischemic zones. Chromanol 293B and HMR 1556 prolonged APD(90) during reperfusion, respectively, by +11 ± 1%, P < 0.01 and +25 ± 4%, P < 0.01 in the NZ and by +13 ± 3%, NS and +31 ± 2%, P < 0.01 in the simulated ischemic zone. Both compounds exhibited neutral arrhythmogenic effects during ischemia or reperfusion. Thus, I(Ks) blockade was neutral on the occurrence of ventricular arrhythmias during ischemia and reperfusion in guinea-pig ventricular tissue.
authors.affiliation: Dipartimento di Fisiopatologia Cardiocircolatoria, Anestesiologia e Chirurgia, Istituto del Cuore Attilio Reale, Laboratory of Biotechnologies Applied to Cardiovascular Medicine, Sapienza Università di Roma, Viale del Policlinico, 155, Rome 00161, Italy. paoloemilio.puddu@uniroma1.it
authors.forename: Paolo Emilio
authors.initials: PE
authors.lastname: Puddu
authors.forename: Laurent
authors.initials: L
authors.lastname: Sallé
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gérard
authors.forename: René
authors.initials: R
authors.lastname: Rouet
authors.forename: Joffrey
authors.initials: J
authors.lastname: Ducroq
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D002839:Chromans / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013610:Tachycardia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002839:Chromans; C420023:HMR 1556; D026902:Potassium Channel Blockers; D013449:Sulfonamides; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane