title: KB-R7943, a Na+/Ca2+ exchange inhibitor, does not suppress ischemia/reperfusion arrhythmias nor digitalis arrhythmias in dogs.
abstract: KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) has been used as a pharmacological tool to block the Ca(2+) influx-mode of the Na(+)/Ca(2+) exchanger, which is thought to contribute to ischemia/reperfusion and digitalis arrhythmias. We examined effects of KB-R7943 on ischemia/reperfusion arrhythmias in beagle dogs anesthetized with sodium pentobarbital. Lead II ECG and BP were measured. KB-R7943 or the solvent (10% DMSO) was injected i.v. as a bolus, and 5 min later, the left anterior descending coronary artery was occluded for 30 min followed by reperfusion. KB-R7943 at 5 or 10 mg/kg increased BP without changing ECG parameters including the heart rate. Although 5 mg/kg KB-R7943 deceased the number of arrhythmic beats during the ischemic period, mortality due to ischemia/reperfusion was not decreased by KB-R7943 (5 and 10 mg/kg). KB-R7943 at 5 mg/kg also did not suppress the ouabain-induced arrhythmias. These negative results suggest that Na(+)/Ca(2+) exchange inhibition may not be a useful strategy of suppressing arrhythmias.
authors.affiliation: Department of Pharmacology, University of Yamanashi, Faculty of Medicine, Nakakoma-gun, Yamanashi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Bing-Mei
authors.initials: BM
authors.lastname: Zhu
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kamiya
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nagasawa
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D010042:Ouabain; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D019831:Sodium-Calcium Exchanger; D010042:Ouabain; D013890:Thiourea