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

Effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was examined in a mongolian gerbil model of global cerebral ischemia. Effect of CGP 40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intraperitoneally 30 min before bilateral carotid artery occlusion. At 4 days after the ischemia, locomotor activity was significantly higher in ischemic control mongolian gerbils in comparison with sham-operated mongolian gerbils. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly suppressed the increase of the motility. Seven days after ischemia, ischemic control group was still hyperactive compared to sham-operated group. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly reversed it. The number of survived neurons of ischemic control group was significantly less than that of sham-operated group at 7 days after ischemia. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly increased the number of survived neurons. It is concluded that CGP 40116 is more potent for amelioration of global cerebral ischemic damage than CGS 19755.
 ...
PMID:Neuroprotective effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid in the gerbil model of transient global cerebral ischemia. 923 45

The effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was examined in a cat model of focal cerebral ischemia. Effect of CGP 40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intravenously 30 min before left middle cerebral artery (MCA) occlusion. After MCA occlusion for 8 h, infarction spreaded widely among caudate nucleus prepyriform cortex, amygdala and temporal lobe cortex in the ischemic hemisphere. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly decreased the infarcted area. CGP 40116 was effective in the frontal and central brain, although CGS 19755 showed neuroprotective effect in almost all sites. Thus, the compounds are potent neuroprotectants in focal ischemia.
 ...
PMID:Effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid on focal cerebral ischemia in cat. 923 46

Rats were exposed to hyperbaric oxygen (HBO = 100% oxygen; 2.5 atmospheres absolute pressure) for 6 h. Isovolumic left heart preparations from these animals were subjected to global low flow-ischemia (perfusion rate from 12 ml/min to 2 ml/min for 40 min) and reperfusion. Hearts from rats not exposed to HBO underwent the same ischemic-reperfusion procedure (controls). As compared to control, HBO treatment caused in ex vivo hearts a significant aggravation of cardiac ischemic picture as indicated by a marked increase in left ventricular end diastolic pressure (LVEDP) and reduced post ischemic left ventricular developed pressure (LVDP). At the end of the ischemic and reperfusion periods LVEDP values were 6.8 (p < 0.001) and 8 (p < 0.001) times higher than the corresponding control values. Moreover, LVDP and coronary perfusion pressure (CPP) values were decreased (2.8 times; p < 0.001) and increased (56%; p < 0.001), respectively, as compared to control preparations. These events were also associated with a considerable impairment of the cardiac tissue to generate 6-keto-PGF1 alpha. Treatments of rats with different doses of acetylcysteine (N-acetylcysteine, CAS 616-91-1, NAC; 0.25-0.5-1 g/kg p.o.) before HBO displayed a clear-cut and dose-related protective activity in hearts subjected to ischemia-reperfusion. Also the generating capacity of 6-keto-PGF1 alpha from these hearts were restored according to the dose of NAC employed. When aortic rings from rats exposed to HBO were considered, they showed a reduced capacity to release 6-keto-PGF1 alpha and an increased sensitivity to endothelin-1. At the same time, the relaxant activity of acetylcholine in these tissues was almost lost. Again, NAC treatment of the animals before HBO restored in a dose-dependent way the capacity of the aortic rings to generate 6-keto-PGF1 alpha. This event was paralleled by normalized responses of the preparations to endothelin-1 and acetylcholine. Taken together these results clearly indicate that acute HBO treatment of the rats markedly aggravates the ischemic-reperfusion damage in ex vivo hearts. This event is coupled with a compromised integrity of cardiac and extracardiac endothelial cell functions. The protective activity of NAC observed in this study once more emphasises its therapeutic role in increasing antioxidant defence mechanisms.
 ...
PMID:Influence of acetylcysteine on aggravation of ischemic damage in ex vivo hearts of rats exposed to hyperbaric oxygen. 923 48

The efficacy of post-ischemic treatment with AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl )-4-(3-phenyl-2- propenyl)-piperazine dimaleate, CAS 143110-70-7), a cerebrovascular selective Ca2+ channel antagonist, on brain infarction induced by focal ischemia-reperfusion in rats was evaluated. Focal ischemia was induced by transient occlusion of middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. One day after MCA occlusion (MCAo), brain infarct size was determined by measuring 2,3,5-triphenyltetrazonium chloride-negative stained area of the serial brain sections. The development of cerebral infarction was observed in both regions of cortex and subcortex, such as striatum, caudatum, putamen, hippocampus and corpus callosum. Post-ischemic treatment with AJ-3941 (1 or 3 mg/kg p.o., 10 min and 3 h after the occlusion) significantly reduced the infarct size and volume in the ipsilateral hemisphere in a dose-dependent manner, compared to the solvent control. The reducing effect was observed mainly in the cortical region, and a significant reduction of the subcortical infarct volume was found at the higher dose (3 mg/kg). Post-ischemic treatment with the thromboxane A2 synthetase inhibitor, sodium ozagrel (150 micrograms/kg/min i.v. infusion, between 1 h and 24 h after the MCAo) did not reduce the infarct volume in the hemisphere after ischemia-reperfusion. AJ-3941 had only minimum effect on the elevation of body temperature during ischemia-reperfusion. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain injury after the transient focal cerebral ischemia, and they suggest that AJ-3941 has beneficial effects for treatment of ischemic cerebral damage, such as stroke.
 ...
PMID:Post-treatment of transient focal cerebral ischemia in rats with the novel cerebrovascular-selective Ca2+ channel antagonist (+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-pheny l-2-propenyl)-piperazine dimaleate. 927 34

The protective effect of T-593 ((+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-(methylamino) methyl-2-furyl]methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine, CAS 140695-21-2), a new histamine H2-receptor antagonist, was investigated in rats with acute gastric mucosal injury. An ischemic injury followed by reperfusion was produced by applying a small vascular clamp to the celiac artery for 30 min and then removing it for 60 min. T-593 significantly reduced the area of the lesion in the stomach in a dose-dependent manner, and doses of 0.3 and 3.0 mg/kg inhibited the increase of lipid peroxides in the gastric mucosa after ischemia-reperfusion. A spin-trapping method using 5,5-dimethyl-1-pyrroline-N-oxide showed that T-593 scavenged hydroxyl radicals generated by the hydrogen peroxide-ferrous iron sulfate system. T-593 also significantly inhibited the increase of lipid peroxides induced by free-radical initiators in gastric mucosal homogenates. Thus, the protective effect of T-593 against acute gastric mucosal injury induced by ischemia and followed by reperfusion may result, in part, from its antioxidant properties.
 ...
PMID:Effect of the histamine H2-receptor antagonist (+/-)-(E)-1-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-3'-[2-[[[5-methylamino ) methyl-2-furyl] methyl]thio]ethyl]-2"-(methylsulfonyl)guanidine on acute gastric mucosal injury in rats and its free-radical scavenging activities. 927 43

The effects of TTC-909, the isocarbacyclin methyl ester clinprost (CAS 88931-51-5), incorporated into lipid microspheres, on ischemia-induced decrease in norepinephrine (NE) contents in stroke-prone spontaneously hypertensive rats (SHR-SP) with an occluded middle cerebral artery (MCA) were examined. Occluding of MCA led to infarction limited to the cerebral cortex and also a severe decrease in NE contents in peripheral regions of the infarction. TTC-909 was injected immediately after MCA occlusion, and then daily for 6 consecutive days. As TTC-909 in a dose of 200 ng/kg significantly (p < 0.05) prevented decreases in NE contents, TTC-909 may have cytoprotective effects on neuronal damage related to ischemia in humans.
 ...
PMID:Effects of the isocarbacyclin methyl ester clinprost incorporated into lipid microspheres, in focal ischemia of stroke-prone spontaneously hypertensive rats. 942 73

The syntheses of cariporide mesilate ((4-isopropyl-3-methanesulfonyl-benzoyl) guanidine methanesulfonate, HOE 642, CAS 159138-81-5), currently being clinically investigated as a protective drug in cardiac ischemia and reperfusion states, and of HOE 694 ((3-methanesulfonyl-4-piperidino-benzoyl)guanidine methanesulfonate, CAS 149725-40-6), widely used as a physiological and pharmacological research tool in studies comprising Na+/H+ exchange (NHE) inhibition, are described. Additionally, their selectivity on the different subtypes is disclosed.
 ...
PMID:Synthesis of the highly selective Na+/H+ exchange inhibitors cariporide mesilate and (3-methanesulfonyl-4-piperidino-benzoyl) guanidine methanesulfonate. 942 74

Cardiovascular effects of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine), a calcium channel blocker, were investigated in anesthetized normal dogs and dogs with acute heart failure (AHF), and compared with those of nitroglycerin (NTG). In open-chest anesthetized dogs, NIC (0.1-10 micrograms/kg/min i.v.) dose-dependently increased cardiac output (CO) and coronary blood flow as well as decreased mean blood pressure (MBP). NIC had no effect on heart rate (HR) or maximum rate of rise of left ventricular pressure (max. dp/dt). In contrast (0.1-10 micrograms/kg/min i.v.) decreased MBP, but did not change the other cardiovascular parameters. NIC and NTG did not prolong PQ, QRS or QTc intervals. In addition, NIC was effective in the presence of dobutamine. In the anesthetized dog model of ischemic AHF induced by coronary ligation, and ischemia/angiotensin II-induced AHF, NIC (1 and 3 micrograms/kg/min i.v.) increased CO and stroke volume, and reduced total peripheral resistance without decreasing HR or cardiac contractility. Furthermore, in the ischemia/angiotension II-induced AHF model, NIC decreased left ventricular end-diastolic pressure (LVEDP). In contrast, NTG (1-10 micrograms/kg/min i.v.) decreased LVEDP in both AHF models; but did not increase CO. These results suggest that NIC improves hemodynamics in dogs with AHF mainly by reducing afterload without adversely affecting the cardiac contractility or conduction system, while NTG exerts its effect on AHF by reducing preload. NIC injection would thus appear to be beneficial in the treatment of AHF.
 ...
PMID:Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 1: Hemodynamic effects in normal dogs and dogs with acute heart failure. 954 21

The protective effect of taurine (CAS 107-35-7) against reperfusion-induced arrhythmias has been investigated in isolated perfused rat heart (Langendorff method). Partial ischemia was induced by occlusion of left descending artery for 15 min, followed by 10 min reperfusion. Left ventricular pressure and epicardial ECG were continuously monitored before and during ischemia and reperfusion. A control group was submitted to partial ischemia without taurine treatment. Three groups were submitted to partial ischemia, under taurine (10 mmol/l) treatment in the Krebs-Henseleit perfusing buffer during ischemia only (group 1), at reperfusion (group 2) and throughout the experimental period (group 3). Malondialdehyde levels were measured as an index of lipid peroxidation and heart muscle damage. The incidence of irreversible ventricular fibrillation was significantly diminished from 83% (control group) to 36% in group 1, 42% in group 2 and 16% in group 3. The incidence of premature ventricular beats and ventricular tachycardia at reperfusion as well as malondialdehyde levels were significantly decreased under taurine treatment. The results indicate that taurine protects ischemic heart against reperfusion-induced arrhythmias, via both its properties as membrane stabilizer and oxygen free radical scavenger.
 ...
PMID:Protective effects of taurine against reperfusion-induced arrhythmias in isolated ischemic rat heart. 960 77

The abilities of 2-(2-methylphenyl)-5,7-dimethoxy-4-quinolyl carbonylguanidine dihydrochloride (CAS 181048-29-3, MS-31-050) and 2-phenyl-8-(2-methoxyethoxy)-4-quinolyl carbonylguanidine bismethanesulfonate (CAS 181048-36-2, MS-31-038) in inhibiting Na(+)-H+ exchange, ischemia- and reperfusion-induced injury were determined and compared with those of 4-isopropyl-3-methylsulfonylbenzoyl guanidine methanesulfonate (CAS 159138-81-5, IMGM), a selective inhibitor of Na(+)-H+ exchange. MS-31-050 and IMGM exhibited comparable inhibitory effects on Na(+)-dependent pH recovery and antiarrhythmic effects during ischemia in anesthetized rats. In rats subjected to ischemia and reperfusion, MS-31-050 (10 mg/kg i.v.) significantly reduced the infarct size when given prior to the onset of ischemia. However, postischemic treatment with either MS-31-050 or IMGM failed to protect reperfused hearts. In contrast, MS-31-038 reduced the infarct size dramatically from 65.4 +/- 7.4% in control to 29.9 +/- 11.6% at 3 mg/kg and 9.8 +/- 3.4% at 10 mg/kg even when administered before the onset of reperfusion. These results suggest the beneficial effects of Na(+)-H+ exchange inhibitors on myocardial ischemia/reperfusion injury.
 ...
PMID:Effects of MS-31-038, a novel Na(+)-H+ exchange inhibitor, on the myocardial infarct size in rats after postischemic administration. 1033 48


<< Previous 1 2 3 4 5 Next >>