Antiarrhythmic effects of HOE642, a novel Na(+)-H+ exchange inhibitor, on ventricular arrhythmias in animal hearts

European Journal of Pharmacology
Y X XueK Hashimoto

Abstract

HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na(+)-H+ exchange subtype 1 inhibitor, was investigated for its possible antiarrhythmic effects on coronary artery ligation/reperfusion and ouabain-induced arrhythmias in the canine heart which may occur after intracellular Ca2+ overload. Also, the effects of HOE642 on coronary artery ligation/reperfusion of the left coronary artery were tested in rat hearts. HOE642 (1 mg/kg) significantly suppressed the occurrence of fatal ventricular fibrillation during coronary artery ligation and after reperfusion in dogs (2 out of 8 dogs in the treated group compared to 7 out of 8 dogs in the control group, P < 0.05), but did not suppress ventricular premature contractions and ventricular tachycardia during ischemia in the canine hearts. HOE642 at the same dose markedly reduced the total duration and the incidence of reperfusion-induced ventricular tachycardia, and the incidence and mortality of reperfusion-induced ventricular fibrillation in rats (ventricular tachycardia duration, 159 +/- 12 s to 21 +/- 8 s, P < 0.01; ventricular tachycardia, 100% to 69%; ventricular fibrillation, 89% to 0%, P < 0.01; mortality, 89% to 11%, P < 0.01). The heart rate, blood ...Continue Reading

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Citations

Sep 11, 1999·The American Journal of Cardiology·M Avkiran
Feb 13, 1999·European Journal of Pharmacology·H R LuF De Clerck
Feb 10, 2000·European Journal of Pharmacology·H NaitoK Hashimoto
Jul 23, 1999·Annals of the New York Academy of Sciences·J Orlowski
Nov 4, 2000·Expert Opinion on Investigational Drugs·M Karmazyn
Mar 11, 2005·Autonomic & Autacoid Pharmacology·A T Demiryürek, S Demiryürek
Jan 4, 2005·European Journal of Pharmacology·Yoshinobu NagasawaKeitaro Hashimoto
Apr 13, 2005·International Journal of Cardiology·A L MoensC J Vrints
Jan 10, 2002·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·K Hashimoto
Dec 11, 1999·Journal of Molecular and Cellular Cardiology·M Hartmann, U K Decking
Apr 6, 2007·Journal of Pharmacological Sciences·Keitaro Hashimoto
Apr 28, 1999·Journal of Cardiovascular Pharmacology·A TakaharaR Yoshimoto
Jan 5, 2000·The Journal of Biological Chemistry·L Counillon, J Pouysségur
Nov 22, 2019·Frontiers in Cardiovascular Medicine·Stefan Michael SattlerThomas Jespersen
Feb 10, 1999·The American Journal of Physiology·K PetreccaA Shrier
Nov 22, 2000·American Journal of Physiology. Heart and Circulatory Physiology·T G HamptonJ P Morgan

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