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)

The spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) is an improved ESR probe to assess superoxide (O2*-) formation in the postischemic heart. We recently found that DEPMPO pretreatment improves recovery of cardiac function with the concomitant inhibition of postischemic O2*- production. By perfusing diethyl methylphosphonate MeP(O)(OEt)2 to ischemic-reperfused isolated rat hearts, we provide hemodynamic evidence that this preservation, which exerts during ischemia, is in fact specific to the phosphonate group. Using 31P NMR on intact rat hearts, it was also found that the "phosphonate effect" of DEPMPO is related to the preservation of ATP levels during ischemia, when compared to 5,5-dimethyl-1-pyrroline N-oxide. This mechanism may be a means of reducing the potency of cardiac tissue to produce O2*- during reperfusion.
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PMID:New perspectives on the cardioprotective phosphonate effect of the spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: an hemodynamic and 31P NMR study in rat hearts. 1044 17

We determined whether prior treatment of rats (study 1) with subthreshold doses of iron (no evidence of cardiac tissue overload), or in vitro ischemic pre-conditioning (IP: 5 min. Ischemia (I)/5 min. Reperfusion (R) x 2 cycles) of hearts from untreated rats (study 2), can modulate redox-active cardiac tissue iron levels or distribution, leading to alterations in post-ischemic lipid peroxidation-derived free radical (FR) production and severity of reperfusion injury. In study 1, rats received biweekly i.p. injections of 0 (saline=S), 3, 6, or 12 mg FeCl3/ml for 3-wks prior to imposing 30 min. I/15 min. R in vitro. The highest dose caused no elevations in plasma or heart tissue Fe levels, but did further reduce post-ischemic recoveries of left ventricular developed pressure (17% lower), cardiac work (57%) and output (54%), and increased effluent lipid hydroperoxides (2.1-fold) compared to the S-group. Post-ischemic FR production was assessed in toluene-extracted effluent by ESR spectroscopy and alpha-phenyl-N-tert butylnitrone (PBN=2.5 mM perfusate) spin trapping. PBN/alkoxyl (alphaH=1.90 G, alphaN=13.63 G) was the dominant signal detected in all groups; however, Fe-treated groups displayed significant dose-dependent increases in total alkoxyl content (3, 6, 12 mg/ml: 1.8-, 2.3-, 2.7-fold higher) compared to the S-group. These data suggest that even mild, non-overloading doses of iron can be functionally and oxidatively detrimental to hearts when an I/R stress is imposed. In study 2, isolated hearts from untreated rats were exposed to two-IP cycles: during IP, total effluent iron content (atomic absorption) increased 11.4-fold compared to control and analysis of cardiovascular tissue iron distribution (X-ray microanalysis) suggested that iron loss from capillary endothelium was far greater than from tissue myocytes. Moreover, iron-catalyzed production of alkoxyl radicals following severe I/R stress (40 min. I/15 min. R) was substantially lower (73%) in IP hearts compared to the non-IP counterparts. These preliminary findings suggest that cardioprotection resulting from IP may, in part, be related to IP-induced release of cardiovascular endothelial iron (redox-active) prior to imposing severe I/R stress.
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PMID:Cardiac tissue iron: effects on post-ischemic function and free radical production, and its possible role during preconditioning. 1115 77

A traditional Chinese herbal medicine, Qizhu Tang (QZT) was studied for its in vitro antioxidant activity and the effect on cerebral oxidative damage after forebrain ischemia followed by reperfusion in rats. The QZT decoction was shown to have strong hydroxyl radical (*OH) scavenging activity (approx. 0.1 mM as Trolox equivalent) when determined by ESR using DMPO as a spin trap reagent and H2O2/UV as the *OH source. When the QZT decoction was injected into rat duodenum 2 h before cerebral ischemia, the oxidative brain damage after 45 min reperfusion was strongly inhibited in terms of two biochemical indications, thiobarbituric acid reactive substance formation and the loss of glutathione peroxidase. Since the QZT formula consists of 4 herbal constituents (Rhizoma atractylodis, Poria, Radix notoginseng and Radix astragali), each of the component herbs and their combinations were also examined for their protective effects on the cerebral ischemia/reperfusion injury and the effects were compared with their in vitro antioxidant potential. Although some of the incomplete formulas showed as strong antioxidant activities as complete QZT in vitro, only the complete QZT formula was effective in preventing cerebral oxidative injury in rats, and other preparations showed limited activity in vivo.
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PMID:Antioxidant potential of qizhu tang, a chinese herbal medicine, and the effect on cerebral oxidative damage after ischemia reperfusion in rats. 1137 80

Implication of AT1 receptors (AT1R) in functional and metabolic modifications associated with ischemia-reperfusion is not clearly defined. The aim of this study was:--to evaluate the role of AT1R in isolated rat hearts subjected to a reversible ischemia:--to establish possible relationships between functional parameters and oxidative stress during reperfusion period. Isolated hearts perfused by the Langendorff method underwent 30 min of a global total ischemia followed by 30 min of reperfusion. Functional parameters and LDH release were recorded under AT1R stimulation by angiotensin II (AII) (10(-7) M) and/or AT1R blockade by losartan (10(-6) M). Quantification of oxidative stress was performed in coronary effluents 1) directly, using ESR spectroscopy associated with PBN spin trapping and 2) indirectly, using HPLC method to detect glutathione (GSH + GSSG) release. Our results showed that All induced vasoconstrictive and negative inotropic effects during control period. During reperfusion. All reduced incidence of reperfusion arrhythmia and LDH release. From the onset of reperfusion, a large and long lasting release of alkyl/alkoxyl radicals and glutathione was detected and the intensity of the oxidative stress was not significantly changed in the groups treated will All and/or losartan. In conclusion, no relationship has been clearly demonstrated between the oxidative stress intensity and AT1R activation, but these results couldn't exclude the contribution of free radical in some myocardial effects of AT1R stimulation such as vasoconstriction and negative inotropic effect.
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PMID:[Role of AT1 receptors in functional adaptation to ischemia-reperfusion in solated rat hearts in relationship to oxidative stress]. 1157 7

Myocardial stunning, a transient contractile dysfunction that appears following a brief period of ischemia, is at least partly due to the production of oxygen-derived free radicals. The objective of the present study was to determine whether the Ginkgo biloba extract EGb761, which has antioxidant properties in vitro, can attenuate myocardial stunning in vivo. Forty-seven anesthetized open-chest farm pigs underwent 10 min of occlusion of the left anterior descending coronary artery (LAD), followed by 3 hours of reperfusion. They were pretreated with either physiological saline, 100 mg or 300 mg of EGb 761 (Protocol I) or 3 mg or 9 mg of ginkgolide B (GkB) (Protocol II). Contractile function was assessed by sonomicrometry. Both doses of EGb 761 significantly improved recovery of contractile function in the reperfused myocardium with segment shortening averaging 23 +/- 5 % of baseline values at 3 hours post-reflow in controls versus 81 +/- 10 % and 57 +/- 12 % in the EGb100 and EGb300 groups, respectively (p < 0.05 vs control in both cases). In contrast, neither dose of GkB improved functional recovery during reperfusion. ESR experiments revealed that EGb761 resulted in a 59 % decrease in myocardial spin-adduct release during reperfusion (p < 0.05 versus control and GkB groups). A significant 28 % decrease (p < 0.05 vs control group) was also obtained in GkB-treated animals. These results indicate that EGb 761 can attenuate myocardial stunning following a brief ischemic insult in the in situ pig heart by an effect that involves a decrease in the formation of free radicals. As the effect of EGb 761 on functional recovery cannot be explained by the presence of GkB, the beneficial action of the extract on myocardial stunning likely involves complementary effects of both its non-ginkgolide and ginkgolide constituents.
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PMID:Ginkgo biloba extract EGb 761 attenuates myocardial stunning in the pig heart. 1249 70

Giant cell arteritis (GCA) is known to affect the extracranial part of the vertebral arteries. Bilateral vertebral artery occlusion (BVAO) is a rare but serious neurologic condition. We report 3 patients with autopsy-proven (2 patients) or clinically diagnosed (1 patient) GCA causing BVAO. A review of the literature concerning BVAO revealed 5 other cases of BVAO resulting from GCA and 110 cases with underlying arteriosclerotic disease. Our 3 patients (mean age, 66 yr; range, 60-78 yr) with BVAO resulting from GCA all had initial severe headache followed by the onset of stepwise progressive, partly side-alternating neurologic deficits due to bilateral infarctions in the vertebrobasilar circulation territory. This course, more accelerated in BVAO due to GCA than in BVAO of arteriosclerotic origin, seems to be a typical, if not particular, clinical syndrome. BVAO was the first clinical manifestation of GCA in 1 of our patients and in 1 published case. From a clinical view, BVAO resulting from GCA differs from BVAO of arteriosclerotic origin by the much higher mortality rate (75% versus 19%, respectively), the presence of headache (100% versus 22%), fever (50% versus 0%), and elevated erythrocyte sedimentation rate (ESR in all GCA cases >45 mm/h; no data in the arteriosclerotic patient group), but not by the neurologic signs themselves. Therapy of BVAO resulting from GCA is purely empiric. In view of the serious prognosis, we propose treatment with intravenous high-dose glucocorticoids and additional immunosuppression with cyclophosphamide; the use of anticoagulation depends on the individual patient's estimated risk-benefit profile. Although BVAO due to GCA is rare, physicians and especially rheumatologists or neurologists should be aware of this entity because of its high mortality in patients without immediate introduction of a high-dose immunosuppressive therapy. Suspicion of GCA should arise in a patient aged over 50 years with no other vascular risk factors suffering from bilateral symptoms of ischemia in the vertebrobasilar territory, with a quickly progressing stepwise course and with headache, fever, or history of myalgia. ESR and temporal artery biopsy should be performed without delay. Early diagnosis of GCA is necessary for immediate initiation of intensive antiinflammatory and immunosuppressive treatment, without which progressive deterioration and systemic involvement are likely to be fatal.
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PMID:Bilateral vertebral artery occlusion resulting from giant cell arteritis: report of 3 cases and review of the literature. 1254 6

To date, the involvement of reactive oxygen species in ischemic preconditioning in vivo in rats is not clearly demonstrated. The aim of the present study was to determine whether N-(2-mercaptopropionyl)glycine (MPG), a cell-diffusible hydroxyl radical scavenger, and carnosine, a potent singlet oxygen quencher, could block protection afforded by a single cycle of ischemic preconditioning in vivo in the rat. An ESR study was first performed to validate in vitro the specific antioxidant properties of carnosine and MPG. In a second set of experiments, open-chest rats were subjected to 30 min of left coronary occlusion followed by 60 min of reperfusion. Preconditioning was elicited by 5 min of ischemia and 5 min of reperfusion. Neither MPG (1-h infusion, 20 mg/kg) nor carnosine injection (bolus, 25 micro mol/rat) affected infarct size. The infarct size-limiting effect of preconditioning was completely blunted by MPG, whereas carnosine did not alter the cardioprotection. It is concluded that free radicals and especially hydroxyl radicals could be involved in the adaptive mechanisms induced by a single cycle of preconditioning in vivo in rats.
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PMID:Involvement of reactive oxygen species in cardiac preconditioning in rats. 1262 23

A number of researchers have reported that free radicals generated in the brain are involved in various brain dysfunctions, including ischemia-reperfusion injury, brain tumors, and neurodegenerative diseases. It has been reported that the spin probe MC-PROXYL can penetrate the blood-brain barrier and can be useful for evaluating oxidative stress in the brain. Preliminary comparisons were made by ESR imaging of the heads of live mice and isolated rat brains using the spin probe MC-PROXYL and the blood-brain-barrier impermeable probe carbamoyl-PROXYL. The results showed that MC-PROXYL, but not carbamoyl-PROXYL, was widely distributed in the brain. These methods were also applied for the imaging of brains from stroke-prone spontaneously hypertensive rats (SHRSPs). The rapid decay of 2D ESR images of MC-PROXYL in isolated SHRSP-brain was observed, compared to Wistar-Kyoto rats (WKYs), using the ESR imaging system. Furthermore, we provide evidence, by using L-band ESR non-invasively, that the decay rate of MC-PROXYL in the head region is faster in live SHRSPs than in live WKYs. Taken together, the high oxidative stress sustained by oxygen radical generation in SHRSPs may cause the alteration of MC-PROXYL metabolism in the brain. Our results suggest that in vivo ESR could be applied to the assessment of antioxidant effects on oxidative stress in the brain in animal disease models, such as the SHRSP.
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PMID:Measurement of oxidative stress in stroke-prone spontaneously hypertensive rat brain using in vivo electron spin resonance spectroscopy. 1268 6

In vitro, the stable six-membered ring nitroxide 2,2,6,6-tetramethyl-1-piperidine-N-oxyl (TEMPO) is known to protect the ischemic and reperfused myocardium through a mechanism likely to involve the limitation of free radical damage. In vivo, TEMPO's high rate of reduction into diamagnetic nonactive compounds could limit its pharmacological use and its potential as an ESR probe in oxymetry studies. Recently, beta-phosphorylated nitrones and pyrrolidines have been reported to protect against myocardial reperfusion injury better than their nonphosphorylated analogs. Using hemodynamic, metabolic, and enzymatic indices of reperfusion injury, the efficacy of 2-diethoxyphosphoryl-2,5,5-trimethylpyrrolidinoxyl (TMPPO), a five-membered ring beta-phosphorylated nitroxide, has been compared to that of TEMPO when added at a nontoxic concentration (1 mM) in buffer-perfused isolated rat hearts during low-flow ischemia, total ischemia, and reflow. TMPPO, which is five times as hydrophilic and eight times as resistant to reduction in a biological medium as TEMPO, was more effective in reducing postischemic contracture and myocardial enzymatic leakage. Since a diamagnetic analog of TMPPO was far less protective and both nitroxides showed an antilipoperoxidant effect and acted mainly when administered only at reflow, it was proposed that beta-phosphorylated nitroxides such as TMPPO could be interesting alternatives in pharmacological and ESR applications.
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PMID:Hemodynamic and metabolic effects of the beta-phosphorylated nitroxide 2-diethoxyphosphoryl-2,5,5-trimethylpyrrolidinoxyl during myocardial ischemia and reperfusion. 1270 97

Cardioprotection by Mg Sulfate (MgSO4) during ischemia/reperfusion (I/R) is attributed largely to the Mg2+ cation. However, Mg-gluconate (MgGl2) may provide added benefit, possibly through its anion's antioxidant properties. Protective effects of both Mg-salts and their anions during 30 min global I and 50 min R were assessed in Langendorff-perfused (Krebs-Henseleit buffer) rat hearts. Recovery of function was compared between untreated hearts and those receiving supplement (2.4 mM MgGl2, MgSO4, or Na2SO4, or 4.8 mM NaGI) for 5 min prior to I and during the initial 30 min R. The final 20 min R was conducted without supplement. End diastolic pressure (EDP, mmHg) of the 50 min reperfused MgGl2 group (2.6) was lower than MgSO4 (16.2) and untreated (35.6) groups, and the NaGI group (25.2) was considerably lower than Na2SO4 (38.8). Recovery of developed pressure (% preischemic DP) at the onset of R for MgGl2 (74.9) was greater than MgSO4 (37.9) and untreated (33.2). After 50 min, MgGl2 (77.9) and MgSO4 (66.9) provided protection compared to untreated (51.8). In separate studies, ESR spin trapping with alpha-phenyl-N-tert-butylnitrone (3 mM PBN) showed that I/R alkoxyl radical production was reduced with MgGl2 (0.0 vs. 2.4 vs. 3.6 mM: 184 vs. 97 vs. 54.8 nM/g tissue x min) to a greater extent than seen with MgSO4 (3.6 mM: 108). Additional studies suggest that Gl(1-), unlike SO4(2-), may scavenge hydroxyl radicals, accounting for the added protection. MgGl2 treated hearts exhibited less postischemic dysfunction and oxidative injury compared to MgSO4, suggesting the contribution of Gl(1-) to cardioprotection.
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PMID:Mg-gluconate provides superior protection against postischemic dysfunction and oxidative injury compared to Mg-sulfate. 1270 53


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