title: Effects of purified endogenous inhibitor of the Na+/Ca2+ exchanger on ouabain-induced arrhythmias in the atria and ventricle strips of guinea pig.
abstract: Previous studies demonstrated that the purified endogenous inhibitor (NCX(IF)) of the cardiac Na(+)/Ca(2+) exchanger (NCX1) has the capacity to modulate cardiac muscle contractility. Here, we tested the effects of purified NCX(IF) on arrhythmias induced by ouabain in the atria and ventricle strips of guinea pig. For the sake of comparison NCX(IF) was compared to lidocaine and KB-R7943. In the ventricle strip, NCX(IF) ( approximately 10 U/ml) results in rapid, complete and stable inhibition of ouabain-induced arrhythmias (the inhibition of arrhythmia is not followed by revival of irregular contractions). Under similar experimental conditions the atria strips require somewhat higher doses of NCX(IF) (25-50 U/ml) for complete suppression of arrhythmia. In the atria strip, NCX(IF) (10-25 U/ml) increases the threshold dose (1 microM) of ouabain for arrhythmia onset 2.2+/-0.5-fold (n=5, p<0.05) as well as prolongs the lag-phase for arrhythmia appearance 4.0+/-0.5-fold (n=5, p<0.01). The lag period for arrhythmia onset was also lengthened (2.0+/-0.4-fold) by NCX(IF) in the ventricle strips (n=6, p<0.002). At low frequency of pacing (1 Hz), all three tested substances, lidocaine, KB-R7943, and NCX(IF) can effectively suppress the ouabain-induced arrhythmia. However, at higher frequency (2 Hz), lidocaine is ineffective in suppressing arrhythmia, whereas KB-R7943 becomes pro-arrhythmic. In contrast to reference drugs, NCX(IF) retains its anti-arrhythmic capacity at high frequencies, either in the atria (n=6, p<0.01) or ventricle (n=5, p<0.05) strips. In conclusion, NCX(IF) results in rapid, effective and stable suppression of arrhythmia both in the atria and ventricle preparations under conditions at which the reference drugs become ineffective.
authors.affiliation: Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Ramat-Aviv 69978, Israel.
authors.forename: Beni
authors.initials: B
authors.lastname: Shpak
authors.forename: Yana
authors.initials: Y
authors.lastname: Gofman
authors.forename: Chagit
authors.initials: C
authors.lastname: Shpak
authors.forename: Reuben
authors.initials: R
authors.lastname: Hiller
authors.forename: Liron
authors.initials: L
authors.lastname: Boyman
authors.forename: Daniel
authors.initials: D
authors.lastname: Khananshvili
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D002316:Cardiotonic Agents; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013327:Strophanthidin; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D013327:Strophanthidin; D008012:Lidocaine; D013890:Thiourea