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)

Naftidrofuryl is an antiserotonin S2-specific agent, with the three following effects: (1) peripheral vasodilatation, (2) antiaggregation and (3) increase in cellular metabolic. These effects could be interesting in the management of the optic nerve ischemia of glaucomatous patients and especially of those with normal tension glaucoma. The administration of 2 x 200 mg/day of naftidrofuryl during 6 weeks to 12 patients with normal tension glaucoma has shown an improvement of the visual acuity and the visual field compared with a 6-week period of placebo administration, with a double-blind study method. It suggested that naftidrofuryl might be administered as a useful complement to conventional hypotensive therapy, since it acts positively on the glaucomatous optic nerve damage.
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PMID:Double-blind study in the treatment of normal tension glaucoma with naftidrofuryl. 208 56

The effects of naftidrofuryl on postischemic neuronal damage and on local cerebral blood flow (LCBF) were examined in a rat model of forebrain ischemia (occlusion of carotid arteries and hypotension). Ischemia was induced for 10 min. LCBF was measured after 2 and 10 min of recirculation. A histological evaluation of cell loss in the hippocampal areas was performed 7 days after ischemia. Naftidrofuryl (10 mg/kg) was administered intraperitoneally 15 min before ischemia. The drug reduced the percentage of necrotic neurons in the CA1 and CA4 sector of the hippocampus, while the LCBF of these hippocampal sections was not significantly altered. Thus, naftidrofuryl is suggested to protect hippocampal neurons against ischemic damage mainly by a direct effect on brain parenchyma.
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PMID:Naftidrofuryl protects neurons against ischemic damage. 275 48

The effect of a serotonin S2 antagonist, naftidrofuryl, on ischemic neuronal damage was examined in the gerbil. Naftidrofuryl was injected i.p. 5 min prior to a single 5-min forebrain ischemia or immediately after each of three 2-min forebrain ischemic insults at 60-min intervals. In both groups the number of intact hippocampal CA1 neurons were significantly higher than in the saline-treated group. These results indicate that serotonin S2 antagonists have a protective effect against ischemic neuronal damage.
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PMID:A serotonin S2 antagonist, naftidrofuryl, exhibited a protective effect on ischemic neuronal damage in the gerbil. 277 23

Transcutaneous partial oxygen pressure on dorsum of foot was determined and capillaroscopy of big toes performed before and after infusions of naftidrofuryl (200 mg/l/h) and of 5% levulose to 30 patients with obliterative arterial disease of lower limbs, stages II to IV (10 patients in each stage). Naftidrofuryl provoked an increase in cutaneous partial oxygen pressure of 26.8 to 36.4 mm Hg (p less than 0.001) whereas no significant change was noted after 5% levulose. In addition, density of visible capillaries increased from 23.5 to 26.1/mm2 with naftidrofuryl. Severe stages of ischemia, evaluated as described by Fagrell, were improved by naftidrofuryl treatment. These findings suggest a favorable action of naftidrofuryl on cutaneous microcirculation distal to arterial obliteration at all Fontaine's stages.
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PMID:[Transcutaneous measures of oxygen partial pressure and capillaroscopic parameters as affected by naftidrofuryl in patients with obliterative arteriopathies, Fontaine stages II-IV]. 355 15

Male Wistar rats were subjected to forebrain ischemia of 10 min duration by clamping both common carotid arteries and simultaneously lowering systemic blood pressure to 40 mm Hg by exsanguination. Recovery was achieved by removing the arterial clamps and reinfusing the blood. Cortical levels of high-energy phosphates and glycolytic substrates were determined enzymatically. Naftidrofuryl (10 or 20 mg/kg i.p.) or ketamine (5 mg/kg i.v.) were applied 30 min prior to the induction of ischemia. S(-)-Emopamil (4 mg/kg) or nimodipine (50 micrograms/kg) were administered by intravenous infusion over 30 min. Nimodipine and emopamil increased the blood glucose level and lowered preischemic blood pressure. Under control conditions, a tendency toward a higher cortical glucose level was observed in treated brains. Brain energy stores were exhausted after ischemia in control and treated animals to the same degree. Lactate levels, however, were higher in emopamil-treated animals. This effect was attributed to the elevated preischemic glucose levels. During the early recovery period, the restoration of high-energy phosphates was accelerated by both calcium entry blockers. Nimodipine and emopamil increased the levels of glucose and glucose-6-phosphate in the early postischemic period. Naftidrofuryl (10 mg/kg) increased the level of creatine-phosphate and ATP after 2 min of recovery. Naftidrofuryl (20 mg/kg) exerted no effect on cerebral energy metabolism, but considerably reduced postischemic blood pressure (possibly thereby masking its ameliorative action). Ketamine accelerated the postischemic restoration of high-energy phosphates. In the conscious rat, local cerebral blood flow (LCBF) was determined with the 14C-iodoantipyrine technique following emopamil (20 mg/kg s.c.) or naftidrofuryl (10 mg/kg i.v.) application.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of cerebroprotective agents on cerebral blood flow and on postischemic energy metabolism in the rat brain. 361 Dec 6

The importance and the various effects of serotonin (5-HT) in cardiovascular diseases are reviewed, with particular emphasis on the involvement of 5-HT2 receptors as mediators of the biological responses of vessels and blood platelets to 5-HT. The importance of 5-HT in peripheral and cerebral ischemia is shown by the key role it plays in inducing vasoconstriction, platelet aggregation, vascular permeability, and cell proliferation. Of particular importance is the 5-HT-selective hypersensitivity developing in vessels/platelets shortly after acute ischemia or early in the development of chronic vascular diseases. The mechanisms of action of naftidrofuryl are described, showing that this drug offers a particularly interesting profile of having both metabolic and vascular effects. Naftidrofuryl improves glucose aerobic metabolism by an action on succinodehydrogenase and improves the blood supply and the ischemic damage of the vessel wall by blocking specifically 5-HT2 receptors. The latter property permits an inhibition of the deleterious, multiple effects of 5-HT at sites of vascular injury, without influencing the general circulatory bed. Therefore, naftidrofuryl appears to be an anticonstrictor and not, as previously thought, a vasodilator. As a consequence, naftidrofuryl has a targeted impact without vasodilator-linked side effects such as hypotension or the steal phenomenon.
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PMID:Serotonin, 5-HT2 receptors, and their blockade by naftidrofuryl: a targeted therapy of vascular diseases. 751 75

Effects of naftidrofuryl oxalate (naftidrofuryl), a 5-HT2 antagonist, on neuronal damage and local cerebral blood flow was examined in a gerbil model of transient forebrain ischemia. Effect of ketanserin tartrate (ketanserin), another 5-HT2 antagonist, on neuronal damage was also examined. Pretreatment with naftidrofuryl or ketanserin prevented hippocampal CA1 neuronal loss after 5 min of transient ischemia. Naftidrofuryl did not improve hippocampal blood flow during and 1 h after transient ischemia determined by [14C]iodoantipyrine autoradiography but increased blood flow in the caudate-putamen 1 h after transient ischemia. The results show that: (1) the 5-HT2 antagonists protect against hippocampal CA1 neuronal damage; and (2) the protective effect of naftidrofuryl may not be caused by a hemodynamic mechanism but by a direct inhibitory neuromodulation via 5-HT2 antagonistic action.
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PMID:Effects of naftidrofuryl oxalate, a 5-HT2 antagonist, on neuronal damage and local cerebral blood flow following transient cerebral ischemia in gerbils. 790 49

The present study was designed to elucidate the possible beneficial effects of naftidrofuryl on ischemia-induced endothelium damage. For this purpose, an in vitro model was developed wherein human endothelial cells isolated from umbilical vein were submitted to hypoxia. Long-term hypoxia incubation (6 h) induced cell mortality, and naftidrofuryl strongly protected endothelial cells against this mortality in a dose-dependent manner and at concentrations as low as 10(-9) M. 66% protection was still observed after 16 h of hypoxia. Naftidrofuryl had to be present during the hypoxia incubation to exert its action; preincubation up to 24 h in the presence of naftidrofuryl could not protect endothelial cells incubated under hypoxia without naftidrofuryl. Short-term hypoxia, which does not induce mortality, strongly activates the endothelial cells with an increase in the cytosolic calcium concentration, in the phospholipase A2 activity, and in the synthesis of prostaglandin and of platelet-activating factor. It also enhances the adherence of polymorphonuclear neutrophils. Naftidrofuryl was able to markedly inhibit this whole cascade of events in a dose-dependent manner. We also demonstrated that naftidrofuryl could block the decrease in ATP concentration that results from the hypoxic conditions. These results indicate that by preserving the energetic level of the cells, naftidrofuryl prevents the activation of endothelial cells and the cell mortality induced by hypoxia. By maintaining an intact endothelium in vivo during ischemia, naftidrofuryl could prevent the further damage induced by leukocyte recruitment and activation.
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PMID:Effects of naftidrofuryl on hypoxia-induced activation and mortality of human endothelial cells. 824 66