Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of a newly synthesized compound, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid] on Na+/H+ or Na+/Ca2+ exchange activity in rat cardiomyocytes, and on radioligand binding with several channels or receptors in membrane preparations, and ischemia/reperfusion injury in isolated perfused rat hearts. In myocytes, SM-20550 concentration-dependently inhibited the recovery from acidosis induced by an NH4Cl prepulse in HCO3(-)-free solution. Its IC50 was 10(-8) M, which was 10 times lower than that of ethylisopropyl amiloride (EIPA). SM-20550 (10(-6) M) did not affect the Na+-dependent Ca2+ influx (Na+/Ca2+ exchange activity) in cardiomyocytes. In the radioligand binding assay, SM-20550 did not have affinity for K+ channel, beta-adrenoceptor, adenosine, angiotensin, or endothelin receptors, and had low affinity for Na+ and Ca2+ channels and alpha-adrenoceptors, only at the concentrations of 10(-6)-10(-5) M. In perfused hearts exposed to 40 min of global ischemia and 20 min of reperfusion, SM-20550 (10(-8)-10(-7) M) significantly reduced the elevation of left ventricular end-diastolic pressure during reperfusion, improved the postischemic recovery of developed pressure, and prevented coronary perfusion pressure increase after reperfusion. Furthermore, SM-20550 reduced creatine phosphokinase release during reperfusion and prevented the abnormal gain of tissue Na+ and Ca2+ at the end of reperfusion. These results suggest that SM-20550 is a potent, highly specific Na+/H+ exchange inhibitor, which exerts a protective effect against myocardial ischemia/reperfusion injury. In addition, our data strongly support the hypothesis that Na+/H+ exchange plays an important role in the development of postischemic cardiac dysfunction, most likely by inducing Na+ and Ca2+ overload.
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PMID:SM-20550, a new Na+/H+ exchange inhibitor and its cardioprotective effect in ischemic/reperfused isolated rat hearts by preventing Ca2+-overload. 1083 18

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.
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PMID:Reduction of myocardial infarct size by SM-20550, a novel Na(+)/H(+) exchange inhibitor, in rabbits. 1098 Feb 80

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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PMID:Effect of an Na+/H+ exchange inhibitor, SM-20550, on ischemic preconditioning in rabbits. 1201 48