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)

Critical ischemia due to extensive femoropopliteal occlusive disease often leads to amputation in patients in whom an autologous vein is unavailable for reconstruction. The purpose of this nonrandomized prospective study is to evaluate the usefulness of cryopreserved venous allografts (CPVA) as an arterial substitute in these cases. Between October 1990 and March 1993, long bypass to a tibial or a foot artery using a CPVA was performed in 25 consecutive patients with ulcerations or gangrene. There were 19 women and six men with a mean age of 72 years (range: 51-90). The indication for allograft reconstruction was absence (17 cases) or unsuitability (eight cases) of an autologous vein graft. Greater saphenous vein allografts were harvested from multiple organ donors and frozen at -80 degrees C with 12% dimethylsulfoxide (DMSO). Sixteen patients had undergone one or more previous unsuccessful limb salvage attempts. The plantar arch was absent or incomplete in 16 patients (64%). Patients were followed up prospectively for a mean of 21 months (range: 3-32). One patient died early (32 days) and three patients died late with patent bypasses. Cumulative survival rate was 77% at 1 year and 72% at 2 years. Cumulative secondary patency rate (Kaplan-Meier) was 88% at 1 months, 72% at 6 months, and 52% at 1 year. The cumulative limb salvage rate was 78% at 2 years. When an autologous vein is unavailable, long bypass using a CPVA is a simple, quick, minimally traumatic, economical, and effective method to achieve limb salvage in patients with severe distal arterial occlusive disease. However, CPVA causes immunoreaction and there is a risk of proximal postanastomotic stenosis. Doppler ultrasound surveillance of a subcutaneous graft allows accurate assessment and repair of the abnormalities with no increase in mortality or morbidity.
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PMID:Femorodistal bypass using cryopreserved venous allografts for limb salvage. 914 May 96

Pharmacological experiments have suggested that ocular ischemia, induced by high intraocular pressure in the rabbit, provokes an oxidative stress responsible for functional alteration of the retina. However, the nature of the oxidant chemical species and their mode of generation were not elucidated. The aim of the present studies was to characterize the oxygen-derived free radicals produced during and/or after the hyperpressure period. The technique used was based on electron spin resonance spin trapping analysis of the signals obtained in microdialysates of the retina perfused with the nitrone 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO). The oxidative stress was also evaluated under ischemia and reperfusion periods by measuring the level of ascorbate in the retina via electron spin resonance detection of the ascorbyl free radical-dimethyl sulfoxide (AFR-DMSO) complex. Electroretinograms were recorded to determine the functional consequences of high intraocular pressure and free radical generation. Our results show that superoxide dismutase-inhibitable DEPMPO/hydroxyl radical adducts were generated during the high intraocular pressure period and that the oxidative stress was not increased at reperfusion as assessed by spin trapping and AFR-DMSO measurements. Functional protection provided by free radical scavengers (superoxide dismutase+catalase, TEMPO nitroxide+catalase and dimethylthiourea) against high intraocular pressure-induced electroretinogram alteration confirmed these observations. In conclusion, these experiments demonstrate for the first time by direct measurement that oxygen-derived free radicals are produced by the retina during acute ischemia. This generation could be the explanation for electroretinogram alteration.
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PMID:Free radicals in rabbit retina under ocular hyperpressure and functional consequences. 922 82

Dimethylsulfoxide (DMSO) is a common vehicle used for many drugs used in neuroprotective experiments. DMSO has many biological effects, including antiinflammatory, antioxidant, and local anesthetic effects that could be neuroprotective. To determine if DMSO is neuroprotective in ischemia, DMSO (0, 0.01, 0.03, 0.1, 0.3 and 1.0 ml) was administered intraperitoneally 30 min prior to permanent middle cerebral artery (MCA) occlusion in the rat. Twenty-four hours after MCA occlusion, brains were removed and sectioned. Mean infarction volume was significantly reduced in rats treated with 0.1, 0.3 and 1.0 ml of DMSO compared to saline controls. There was no acute effect of drug treatment upon arterial blood gasses or mean blood pressure. These results suggest that DMSO is neuroprotective in focal cerebral ischemia. Investigators must use appropriate controls when DMSO is used as a vehicle.
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PMID:Dimethylsulfoxide (DMSO) treatment reduces infarction volume after permanent focal cerebral ischemia in rats. 946 72

The effects of dimethyl sulfoxide (DMSO) and ethanol, which share an ability to scavenge free radicals, on ischemia/reperfusion-evoked injury to hippocampal CA1 pyramidal cells were evaluated in the Mongolian gerbil. Ischemia was induced by a 5 min period of bilateral common carotid artery occlusion followed by reperfusion for 5 days. Three groups of unanesthetized gerbils were injected intraperitoneally with either saline, DMSO (2.8 mmol/kg) or ethanol (2.0 mmol/kg) 30 min prior to ischemia. All three groups displayed significant increases in locomotor activity post-ischemia, with no differences between groups. The extent of CA1 pyramidal neuron loss was significantly reduced in the DMSO and ethanol treated gerbils. The results suggest that both agents may be useful as adjuvant therapies in the treatment of cerebral ischemia/reperfusion injury.
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PMID:Protective effects of the free radical scavengers, dimethyl sulfoxide and ethanol, in cerebral ischemia in gerbils. 957 97

Effects of azelnidipine, a dihydropyridine derivative, on stunned myocardium were examined in anesthetized open-chest dogs. The left anterior descending (LAD) coronary artery was ligated for 20 min and then released for 60 min. Dimethyl sulfoxide (DMSO), the solvent of azelnidipine, or azelnidipine (0.03, 0.1 or 0.3 mg/kg) was injected i.v. 20 min before ligation. Segment shortening was determined by sonomicrometry. The levels of high-energy phosphate were measured in 60-min reperfused hearts. Azelnidipine at 0.1 and 0.3 mg/kg significantly decreased diastolic blood pressure and increased % segment shortening. The increase in % segment shortening due to azelnidipine appeared to be abolished by propranolol and atropine pretreatment. Ischemia significantly decreased % segment shortening in all groups. The % segment shortening that had been decreased by ischemia recovered during reperfusion, but did not reach its preischemic level in each group. In the 0.1 and 0.3 mg/kg of azelnidipine-treated dogs, a significant enhancement of % segment shortening recovery during reperfusion was observed, as compared with that in the DMSO-treated dogs. Azelnidipine did not affect the high-energy phosphate levels in 60-min reperfused hearts. In conclusion, azelnidipine improved the contractile dysfunction in stunned myocardium, without any preservation of high-energy phosphate.
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PMID:Effects of azelnidipine, a dihydropyridine calcium antagonist, on myocardial stunning in dogs. 962 15

The so-called terminal negativity (TN) of the DC-potential is a characteristic reaction of neuronal tissue to hypoxia or ischemia. In a previous study on human neocortical slices, two types of TN with flat and steep slopes of rise (< or >10 mV/min) were found with hypoxia. The aim of the present study was to further investigate causes underlying the occurrence of flat and steep TN. Experiments were performed on 23 human neocortical slices (500 micron) resected from 13 patients (epilepsy and tumour surgery). DC-potential and evoked potentials (white matter stimulation) were recorded in layer III. The extracellular potassium concentration ([K+]o) was measured by K+-sensitive microelectrodes. In an interface type chamber, ischemic episodes were induced by oxygen and glucose deprivation. They were terminated when TN had peaked. Both flat and steep TN also existed with ischemic conditions. There was a linear correlation between the slope of rise of TN and the associated slope of rise in [K+]o, respectively, but none regarding latencies of TN or recovery of evoked potentials. Peak levels in [K+]o were 13.9+/-0.9 mmol/l. Compared to control, the slope of rise and latency of TN were clearly increased by addition of dimethyl sulfoxide (DMSO, 0.4%) to the bath solution, whereas nimodipine (40 micromol/l) in 0.4% DMSO had neither an effect on slope of rise of TN nor on latency of TN. As a whole, our observations suggest, that the actual metabolic state determines the occurrence of flat or steep TN.
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PMID:Flat and steep terminal negativity in the DC-potential after deprivation of oxygen and glucose in human neocortical slices. 963 Apr 91

Myocardial ischemia/reperfusion activates a calcium-dependent protease, calpain, in the ischemic myocytes. It is not known whether calpain is involved in the mechanism of ischemia/reperfusion injury in hearts. Thus the purpose of this study was to clarify the effect of a selective calpain inhibitor (CAI) on infarct size and the extent of DNA damage in ischemic/reperfused rat hearts. Rats were divided in four groups (n = 7 each). In saline group, 0.3 ml of saline was administered (i.v.) 10 min before 30-min coronary occlusion followed by 6-h reperfusion. In vehicle group, 0.3 ml of 10% dimethyl sulfoxide (DMSO) was administered 10 min before the 30-min ischemia. CAI (0.5 mg/kg) was administered 10 min before the 30-min ischemia (CAI-A group) and 10 min before the 6-h reperfusion period (CAI-B group). Infarct size was detected with triphenyl tetrazolium chloride, and DNA fragmentation was detected by agarose gel electrophoresis and by in situ nick end labeling (ISEL). Infarct size was significantly smaller in the CAI-A group compared with the vehicle group (13+/-9% vs. 48+/-12%; p < 0.01), and the incidence of ISEL-positive myocyte nuclei in the subendocardial region was significantly reduced in the CAI-A group compared with the vehicle group (26+/-3% vs. 59+/-6%; p < 0.01). However, the effects of CAI in CAI-B group were not significant. Activation of calpain is involved in the mechanism of ischemia/reperfusion injury, and the preischemic administration of CAI was effective in reducing myocardial infarct size and the DNA damage of the myocytes in ischemic/reperfused rat heart.
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PMID:Calpain inhibitor-1 reduces infarct size and DNA fragmentation of myocardium in ischemic/reperfused rat heart. 1021 28

Heat stress (HS) and the subsequent expression of 72 kDa heat shock protein (HSP 72) has been shown to enhance post-ischemic functional recovery and reduce infarct size. Because the synthesis of heat shock proteins involves activation of heat shock transcription factors through phosphorylation, we hypothesized that inhibition of protein kinase C (PKC) would block HS mediated protection and expression of HSP 72 in the heart. Five groups of rats were studied (1) Sham anesthetized, (2) HS group--animals were heat shocked by raising the whole body core temperature to 42 degrees C for 15 min, (3) Vehicle group--HS rats treated with 50% DMSO in saline, (4) PKC inhibitor-treated group--specific PKC antagonist, chelerythrine chloride (5 mg/kg, i.p) given 30 min prior to HS and (5) Vehicle treated control--non-HS rats treated with vehicle prior to ischemia/reperfusion. Hearts were subjected to 30 min of regional ischemia and 90 min of reperfusion 24 h after HS. Risk area was delineated by injection of 10% Evan's blue and infarct size determined using computer morphometry of tetrazolium stained sections. Infarct size (% area at risk) reduced significantly from 49.4 +/- 2.3% (n = 7) in sham to 10.0 +/- 2.5% (p < 0.01) and 9.1 +/- 3.0% in HS and vehicle treated HS groups respectively (p < 0.05) Treatment with chelerythrine prior to HS increased infarct size to 49.4 +/- 2.3% (p < 0.05). Infarct size in chelerythrine-treated non-HS ischemic/reperfused heart was 40.7 +/- 5.4%, which did not differ significantly from vehicle-treated sham group. Western blot analysis demonstrated marked increase in HSP 72 in HS groups (with or without vehicle treatment) and pretreatment with chelerythrine chloride failed to inhibit the expression of HSP 72. The results suggest that HS-induced ischemic tolerance is mediated via PKC pathway and this protection does not appear to be directly related to the expression of HSP 72 in rat heart.
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PMID:Role of protein kinase C and 72 kDa heat shock protein in ischemic tolerance following heat stress in the rat heart. 1039 76

The effect of the selective Na(+)/H(+) antiporter inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) on cerebral ischemia/reperfusion injury was evaluated in the Mongolian gerbil. Ischemia was induced in unanaesthetized gerbils by a 5-min period of bilateral common carotid artery occlusion followed by reperfusion for 6 days. Two groups of gerbils were injected intraperitoneally with either dimethyl sulfoxide (DMSO; 10 microl) or EIPA (5 mg/kg in 10 microl DMSO) 30 min prior to ischemia. The increase in locomotor activity in the EIPA-treated group was significantly less than that of the control group at both 24 h and 6-day post-ischemia. The extent of CA1 pyramidal neuron loss was significantly reduced in the EIPA-treated group in comparison with that of DMSO treated controls. These results suggest that EIPA can protect cerebral neurons from ischemia/reperfusion injury and implicates acidosis and Na(+)/H(+) exchange as a causative factor in such injury.
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PMID:5-(N-Ethyl-N-isopropyl)-amiloride, an Na(+)-H(+) exchange inhibitor, protects gerbil hippocampal neurons from ischemic injury. 1048 15

In an evaluation of the contribution of swelling-induced amino acid release, through the regulatory volume decrease (RVD) process, to cerebral ischemic injury, studies of the role of phospholipases and protein kinases in the response to hyposmotic stress were undertaken using an in vivo rat cortical cup model. Hyposmotic stress induced significant releases of aspartate, glutamate, glycine, phosphoethanolamine, taurine and GABA from the rat cerebral cortex. Taurine release was most affected, exhibiting a greater than 9-fold increase during the hyposmotic stimulus. The phospholipase A2 (PLA2) inhibitors 4-bromophenacyl bromide (1 microM) and 7,7-dimethyleicosadienoic acid (5 microM) had no significant effects on hyposmotically induced amino acid release. AACOCF3 (50 microM), an inhibitor of cytosolic PLA2 decreased taurine release to 84% of DMSO controls. The release of the other amino acids was not affected. The phospholipase C inhibitor U73122 (5 microM) had no significant effects on amino acid release. The protein kinase C (PKC) inhibitor chelerythrine (5 microM) significantly reduced hyposmotically induced taurine release to 72% of saline controls but had no significant effects on the other amino acids. Stimulation of PKC with phorbol 12-myristate, 13-acetate (10 microM) did not significantly change taurine, glutamate, glycine or phosphethanolamine release. The releases of aspartate and GABA were enhanced 2 to 3 fold. Phorbol 12,13-didecanoate (10 microM), another potent stimulator of PKC, significantly increased taurine release to 122% of DMSO controls. The releases of aspartate, glutamate and glycine were enhanced 2.5 to 3.5 fold. Similarly, stimulation of protein kinase A with forskolin (100 microM) significantly increased taurine, aspartate, and glycine release 1.5- to 2-fold compared to DMSO controls. In summary, phospholipases may play a minor role in volume regulation. These studies also support the hypothesis that protein kinases play a modulatory role in the RVD response. The results show that although RVD may play a role, additional mechanisms, including phospholipase activation, must be involved in the ischemia-evoked release of excitotoxic amino acids.
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PMID:Hyposmotically induced amino acid release from the rat cerebral cortex: role of phospholipases and protein kinases. 1053 55


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