Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) is a Na+/H+ exchanger (NHE) inhibitor which has been shown to attenuate cerebral edema in the rat transient focal ischemia model. However, to date, the effect of SM-20220 on cerebral infarction has not been examined. The present experiments were designed to investigate these effects, using both transient and permanent middle cerebral artery (MCA) occlusion models in rats. A dose of 1 mg/kg given intravenously 30 min after the onset of transient MCA occlusion reduced the infarcted area. In the permanent MCA occlusion model, SM-20220 reduced the infarcted area when treatment was delayed for 5, 30 or 60 min after the onset of ischemia. The present results show that NHE has a crucial role in the pathogenesis of ischemic brain damage. This NHE inhibitor may be useful for treating stroke because of its effectiveness with both forms of ischemia and because of its postischemic administration.
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PMID:Delayed treatment of Na+/H+ exchange inhibitor SM-20220 reduces infarct size in both transient and permanent middle cerebral artery occlusion in rats. 1056 21

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.
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PMID:Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts. 1064 13

Endothelial cells play an important role in the physiologic homeostasis of the cerebral circulation. Previously, we showed that the Na+/H+ exchanger (NHE) inhibitor SM-20220 (N-(aminoimino-methyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) improved ischemic brain injury. In this study, we investigated the effect of SM-20220 on cerebrovascular dysfunction after ischemia-reperfusion, focusing on the kinds of dysfunction that involved endothelial function. In cultured bovine brain microvascular endothelial cells (BBMCs), the IC50 value for the NHE activity of SM-20220 was 4 x 10(-8) M. SM-20220 also reduced the cell injury induced by hypoxia/aglycemia-reoxygenation in BBMCs, with statistical significance at 10(-7) M (P<0.05). Next, the effect of SM-20220 on disruption of the blood-brain barrier and cerebral blood flow were evaluated using transient middle cerebral artery (MCA) occlusion models. Intravenous infusion of SM-20220 (0.4 mg/kg per hour for 1 h) attenuated the extravasation of Evans blue, a blood-brain barrier disruption indicator, into cerebral tissue on the day after transient ischemia (P<0.05). The occlusion of the MCA decreased the cerebral blood flow in the MCA territory by about 20%, and only about 45% of the preischemic value was recovered at 1-h reperfusion. A bolus injection of SM-20220 (1 mg/kg, i.v.) improved the postischemic hypoperfusion by about 75%, without causing changes in the systemic blood pressure. These results indicate that the protective effect of NHE inhibitor on ischemic brain injury may be at least partially mediated by the prevention of endothelial dysfunction.
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PMID:Na+/H+ exchange inhibitor SM-20220 improves endothelial dysfunction induced by ischemia-reperfusion. 1132 19

Leukocytes play a key role in ischemia-reperfusion-induced tissue injuries. It has been suggested that blocking the Na+/H+ exchanger improves ischemic injuries such as stroke. In this study, we investigated the effect of the Na+/H+ exchanger inhibitor SM-20220 (N-[aminoiminomethyl]- 1-methyl-1H-indole-2-carboxamide methanesulfonate) on leukocyte-endothelial cell interactions during ischemia-reperfusion. SM-20220 (0.3-1.0 mg/kg i.v.) given after ischemia significantly attenuated the leukocyte adhesion in the mesenteric postcapillary venules that was induced by transient superior mesenteric artery occlusion. At 60 min after reperfusion, the numbers of adherent leukocytes in groups treated with vehicle or SM-20220 (0.3 mg/kg) were 15.1+/-2.9 cells/100 microm/3 min and 3.0+/-0.7 cells/100 microm/3 min (p < 0.01), respectively. In a transient middle cerebral artery occlusion model, i.v. infusion of SM-20220 (0.4 mg/kg per hour) for 1 h, beginning 1 h after the start of occlusion, significantly reduced both the infarct size and the increase in brain myeloperoxidase activity, compared with the vehicle group (p < 0.01 and p < 0.05, respectively). In summary, this is the first evidence that the leukocyte adhesion to the endothelium that is induced by ischemia-reperfusion is attenuated by the inhibition of Na+/H+ exchanger activity in vivo. Our results suggest that Na+/H+ exchanger inhibitors may prevent ischemia-reperfusion injuries such as stroke partly through the attenuation of leukocyte-endothelial cell interactions.
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PMID:Na+/H+ exchange inhibitor SM-20220 attenuates leukocyte adhesion induced by ischemia-reperfusion. 1139 63

The aim of this study was to determine the relationship between the neuroprotective effect of SM-20220 (N(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate) and the timing of its administration in an experimental stroke model. Two hours of occlusion followed by 22 h of perfusion of the left middle cerebral artery (MCA) was performed by inserting a nylon thread into the MCA to occlude it, and pulling the thread to initiate reperfusion. Intravenous infusion of SM-20220 for 1 h reduced the infarct volume at doses of 0.2-0.8 mg/kg in a dose-dependent manner without causing changes in the systemic arterial blood pressure or blood gases, when SM-20220 administration was started 1 h after the onset of occlusion. Administration of SM-20220 at a dose of 0.4 mg/kg also reduced the edema formation induced by ischemia. In contrast, SM-20220 failed to reduce the infarction, even at 1.6 mg/kg, when administration was started 2 h after the onset of occlusion. Thus, the therapeutic time window of SM-20220 for this transient MCA occlusion model is 1 h. Daily administration of SM-20220 (0.4 mg/kg) for the 7 d following 1.5 h of middle cerebral artery occlusion reduced the infarct volume with statistical significance (p<0.05), showing that SM-20220 did not merely delay but prevented ischemic damage.
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PMID:Relationship between the neuroprotective effect of Na+/H+ exchanger inhibitor SM-20220 and the timing of its administration in a transient middle cerebral artery occlusion model of rats. 1145 15

The aim of this study is to clarify whether the activation of a Na(+)/H(+) exchanger (NHE) is tightly concerned with neuronal and glial cell injury induced by ischemia using a selective NHE inhibitor, SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate). Two hours of hypoxia followed by 24 h of reoxygenation induced lactate dehydrogenase (LDH) release, a marker of cell membrane damage, in cultured neurons and glia derived from rats. SM-20220 significantly reduced LDH release in both cells in a concentration-dependent manner, and this effect was statistically significant at concentrations of more than 10(-8) mol/l for neurons and 10(-7) mol/l for glia. A standard NHE inhibitor, 5-(N-ethyl-N-isopropyl)-amiloride, also reduced LDH release in neurons at concentrations of more than 10(-7) mol/l. In a rat transient middle cerebral artery occlusion model, intravenous infusion of SM-20220 reduced cerebral infarction when the serum concentration of SM- 20220 was maintained at about 10(-7) mol/l. These results suggest that the activation of the NHE plays an important role in ischemic neuronal and glial cell injury, and NHE inhibitor may have good therapeutic value for the treatment of ischemic stroke.
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PMID:The Na(+)/H(+) exchanger SM-20220 attenuates ischemic injury in in vitro and in vivo models. 1149 Jan 99