Effect of an Na+/H+ exchange inhibitor, SM-20550, on ischemic preconditioning in rabbits.
The effects of SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid], an Na+/H+ exchange inhibitor, on ischemic preconditioning (IPC) were studied in a rabbit model of myocardial ischemia and reperfusion injury. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). In SM-20550-treated animals, SM-20550 was intravenously administered at 0.03 mg/kg or 0.1 mg/kg before ischemia (30 min). Treatment with SM-20550 at 0.03 mg/kg had a nonsignificant tendency to reduce infarct size (18%). In contrast, 0.1 mg/kg of SM-20550 significantly reduced infarct size by 62%. In animals with IPC, the condition was induced by 2 or 5 min of ischemia and 10 min of reperfusion prior to sustained ischemia (30 min). Although 5 min of IPC significantly reduced infarct size by 72%, 2 min of IPC reduced infarct size by only 27%, which was not significant. The combination of 5 min of IPC and 0.1 mg/kg of SM-20550 significantly reduced infarct size by 78%. This reduction in infarct size was similar to that produced by 0.1 mg/kg SM-20550 or 5 min of IPC alone. Moreover, the combination of 2 min of IPC and 0.03 mg/kg of SM-20550 significantly reduced infarct size by 64%, although neither 0.03 mg/kg SM-20550 nor 2 min of IPC alone reduced infarct size significantly. These results indicate that an Na+/H+ exchange inhibitor SM-20550, does not antagonize the cardioprotective effect of IPC. SM-20550 and IPC appeared to act synergistically to exert a combined cardioprotective effect.
Yamada
K
K
Sumitomo Pharmaceuticals Co., Ltd., Research Center, Osaka, Japan. yamadak@sumitomopharm.co.jp
Matsui
K
K
Yamamoto
S
S
Kitano
M
M
Ohashi
N
N
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D012307:Risk Factors; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000578:Amidines; D007211:Indoles; C121094:SM 20550; D017923:Sodium-Hydrogen Exchangers