title: A possible involvement of sodium channel blockade of class-I-type antiarrhythmic agents in postischemic contractile recovery of isolated, perfused hearts.
abstract: The present study was undertaken to test the hypothesis that the degree of sodium channel blockade by class-I-type antiarrhythmic agents accounts for enhancement of postischemic contractile recovery of ischemic/reperfused hearts. Electrophysiological studies showed that the class-I-type antiarrhythmic agents quinidine, disopyramide, procainamide, lidocaine, mexiletine, flecainide and pilsicainide suppressed the Vmax value of the rat left ventricular muscle cell, a marker of sodium channel blockade, in a concentration-dependent manner. Isolated rat hearts were subjected to 35 min of ischemia and 60 min of reperfusion. Postischemic contractile recovery, which was never detected in untreated hearts, was enhanced in hearts pretreated with these antiarrhythmic agents during the last 3 min before ischemia at concentrations ranging from 3 to 300 microM. Tissue Na, but not Ca, accumulation was also detected in the ischemic heart, and tissue Na and Ca accumulation was observed in the reperfused heart, which suggests that sodium overload occurs during ischemia, followed by sodium and calcium overload during reperfusion. The degree of postischemic contractile recovery seen in the presence of these antiarrhythmic agents was inversely related to tissue Na or Ca accumulation after reperfusion, which suggests that class-I-type antiarrhythmic agents inhibit sodium overload occurring in ischemic/reperfused myocardial cells. A close relationship between postischemic contractile recovery of the perfused heart and depression in the Vmax value of the ventricular muscle was also observed. These results suggest that the ability class-I-type antiarrhythmic agents to inhibit myocardial sodium channels plays a significant role in the enhancement of postischemic contractile recovery of the ischemic/reperfused heart.
authors.affiliation: Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takeo
authors.forename: K
authors.initials: K
authors.lastname: Tanonaka
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: J X
authors.initials: JX
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Kamiyama
authors.forename: N
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: A
authors.initials: A
authors.lastname: Miura
authors.forename: T
authors.initials: T
authors.lastname: Natsukawa
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002412:Cations / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers
chemical_list: D000889:Anti-Arrhythmia Agents; D002412:Cations; D010710:Phosphates; D026941:Sodium Channel Blockers