Reduction of myocardial infarct size by SM-20550, a novel Na(+)/H(+) exchange inhibitor, in rabbits.
The effects of N-(aminoiminomethyl)-1, 4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid (SM-20550), a novel potent Na(+)/H(+) exchanger, and nicorandil, a K(+) channel opener with nitrate-like activity, were studied in a myocardial ischemia and reperfusion injury model. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). Intravenous administration of SM-20550 before ischemia reduced the infarct size by approximately 30-70% in a dose-dependent manner, with a significant reduction in serum creatine phosphokinase activity. Similarly, intravenous administration of nicorandil before ischemia reduced the infarct size by 33% with a significant reduction in serum creatine phosphokinase activity. Moreover, intravenous administration of SM-20550 after ischemia resulted in a significant, approximately 20-40% reduction in the infarct size, but the administration of nicorandil after ischemia did not reduce the infarct size. These results indicate that SM-20550 reduced myocardial necrosis when administered either before or after ischemia.
Yamada
K
K
Sumitomo Pharmaceuticals Co., Ltd., Research Center 1-98 Kasugadenaka 3-chome, Konohana-ku, 554-0022, Osaka, Japan.
Matsui
K
K
Satoh
K
K
Kitano
M
M
Yamamoto
S
S
Ohashi
N
N
D000578:Amidines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D020108:Nicorandil / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000578:Amidines; D000889:Anti-Arrhythmia Agents; D007211:Indoles; D020011:Protective Agents; C121094:SM 20550; D017923:Sodium-Hydrogen Exchangers; D020108:Nicorandil; D003402:Creatine Kinase