Effects of MS-31-038, a novel Na(+)-H+ exchange inhibitor, on the myocardial infarct size in rats after postischemic administration.
The abilities of 2-(2-methylphenyl)-5,7-dimethoxy-4-quinolyl carbonylguanidine dihydrochloride (CAS 181048-29-3, MS-31-050) and 2-phenyl-8-(2-methoxyethoxy)-4-quinolyl carbonylguanidine bismethanesulfonate (CAS 181048-36-2, MS-31-038) in inhibiting Na(+)-H+ exchange, ischemia- and reperfusion-induced injury were determined and compared with those of 4-isopropyl-3-methylsulfonylbenzoyl guanidine methanesulfonate (CAS 159138-81-5, IMGM), a selective inhibitor of Na(+)-H+ exchange. MS-31-050 and IMGM exhibited comparable inhibitory effects on Na(+)-dependent pH recovery and antiarrhythmic effects during ischemia in anesthetized rats. In rats subjected to ischemia and reperfusion, MS-31-050 (10 mg/kg i.v.) significantly reduced the infarct size when given prior to the onset of ischemia. However, postischemic treatment with either MS-31-050 or IMGM failed to protect reperfused hearts. In contrast, MS-31-038 reduced the infarct size dramatically from 65.4 +/- 7.4% in control to 29.9 +/- 11.6% at 3 mg/kg and 9.8 +/- 3.4% at 10 mg/kg even when administered before the onset of reperfusion. These results suggest the beneficial effects of Na(+)-H+ exchange inhibitors on myocardial ischemia/reperfusion injury.
Banno
H
H
Institute of Biological Science, Mitsui Pharmaceuticals, Inc., Chiba, Japan.
Fujiwara
J
J
Hosoya
J
J
Kitamori
T
T
Mori
H
H
Yamashita
H
H
Ikeda
F
F
D000758:Anesthesia; D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013610:Tachycardia / Q000209:etiology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control
D004791:Enzyme Inhibitors; D011804:Quinolines; D017923:Sodium-Hydrogen Exchangers; C119847:MS 31-038