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.
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