title: Reduction of myocardial infarct size by SM-197378, a novel Na+/H+ exchange inhibitor, in rabbits.
abstract: The effects of SM-197378, 2-[[[amino(imino)methyl]amino]carbonyl]-1-methyl-4-trifluoromethyl-1H-indol-7-yl=hydrogen=sulfate monohydrate, a novel potent Na+/H+exchange inhibitor, on heart injury were studied using a rabbit model involving 30 min of myocardial ischemia and 5 h of reperfusion. Intravenous administration of SM-197378 before ischemia reduced the infarct size by approximately 30-50% in a dose-dependent manner. This anti-necrotic effect was achieved without significant hemodynamic changes. Moreover, administration of SM-197378 before reperfusion also resulted in a significant, approximately 30-40%, reduction in the infarct size. The anti-necrotic effect of pre-ischemic bolus treatment with SM-197378 was compared with that of nicorandil, a K+channel opener with nitrate-like activity, and ischemic preconditioning. With 30 and 60 min of ischemia, the anti-necrotic effects of SM-197378 and ischemic preconditioning were similar and superior to that of nicorandil. With 90 min of ischemia, the anti-necrotic effect of SM-197378 was superior to that of ischemic preconditioning.
authors.affiliation: Sumitomo Pharmaceuticals Co., Ltd., Research Division, Japan. yamadak@sumitomopharm.co.jp
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yamada
authors.forename: Kazuki
authors.initials: K
authors.lastname: Matsui
authors.forename: Shoji
authors.initials: S
authors.lastname: Ogawa
authors.forename: Setsuko
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Masaya
authors.initials: M
authors.lastname: Mori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitano
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohashi
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D019194:Ischemic Preconditioning; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000150:complications; D009206:Myocardium / Q000473:pathology; D020108:Nicorandil / Q000494:pharmacology; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C507276:2-(((amino(imino)methyl)amino)carbonyl)-1-methyl-4-trifluoromethyl-1H-indol-7-yl-hydrogen-sulfate monohydrate; D007211:Indoles; D017923:Sodium-Hydrogen Exchangers; D014665:Vasodilator Agents; D020108:Nicorandil