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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen-derived free radicals have been implicated in myocardial ischemia-reperfusion injury. It has been proposed that deferoxamine, an iron chelator, improves myocardial preservation by reducing the iron-catalyzed production of the hydroxyl radical. The objectives of this study were to define the appropriate timing of iron chelation therapy and the dose-response properties of deferoxamine. Isolated working rat hearts were subjected to 25 minutes of normothermic global ischemia. Deferoxamine was given as pretreatment (n = 39; doses of 10 or 30 mg/kg), added to cardioplegic solution (n = 43; doses 0.46 to 1.90 mmol/L), or administered upon reperfusion (n = 52; doses 0.15 to 0.76 mmol/L) and compared with saline controls (n = 25). Deferoxamine pretreatment improved survival at each dose from a control value of 44% to 71% and 72% (p less than 0.05), respectively. A cardioplegia dose of 0.46 mmol/L improved survival from 48% to 75%. Higher doses reduced survival and implied a toxic effect. Reperfusion therapy did not alter survival. Regardless of time of administration, deferoxamine did not improve ventricular function or adenosine triphosphate levels. Deferoxamine given as pretreatment 1 hour before ischemia at doses of 30 mg/kg, and perhaps as low as 10 mg/kg, significantly improved survival. The addition of deferoxamine to cardioplegic solution was safe and may be protective at approximately 0.50 mmol/L; however, toxicity should be considered at concentrations greater than 0.76 mmol/L. These data support the postulate that iron catalysis is involved in the production of oxygen-derived free radicals during ischemia-reperfusion injury. We conclude that pretreatment before ischemia is an important component of iron chelation therapy in myocardial preservation.
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PMID:Iron chelation in myocardial preservation after ischemia-reperfusion injury: the importance of pretreatment and toxicity. 154 57

The lipid peroxidation inhibitor, U74006F, was tested for neuroprotective properties using the rat four-vessel occlusion model. Adult Wistar rats (136) were randomized to receive pretreatment with either vehicle or U74006F, and exposed to either 15 min (n = 103) or 5 min (n = 33) of transient but severe forebrain ischemia. Surviving criterial animals were reperfused for 72 h, and in the multidose experiments, animals were injected with repeated doses of U74006F or vehicle during the reperfusion period. Vehicle-treated animals exposed to 15 min of ischemia sustained 60 +/- 35% (n = 16) CA1 pyramidal cell necrosis whereas U74006F-treated animals lost 61 +/- 30% (3 mg/kg, n = 9), 42 +/- 35% (10 mg/kg, n = 15), 62 +/- 28% (5 x 10 mg/kg, n = 10), and 74 +/- 30% (8 x 10 mg/kg, n = 10) of CA1 pyramidal cells. No improvement was seen in the injury to cortex or striatum with either pre- or pre- and posttreatment with U74006F. For animals suffering 5 min of transient forebrain ischemia, vehicle-treated rats lost 19 +/- 26% (n = 14), whereas U74006F-treated (8 x 10 mg/kg) animals lost 36 +/- 39% (n = 15) of CA1 neurons. In addition, no protection was discerned in the mildly injured striatum or cortex of these animals. Given the potent effect of U74006F in inhibiting iron-dependent lipid peroxidation in vitro, we question the importance of oxy radicals in the mechanism of postischemic selective neuronal injury in vivo.
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PMID:Failure of the lipid peroxidation inhibitor, U74006F, to prevent postischemic selective neuronal injury. 154 97

Postischemic reperfusion is known to cause iron-mediated peroxidation of polyunsaturated fatty acids in membranes, including mitochondrial membranes, in the brain cortex. Consequently, we tested the hypothesis that this radical-mediated damage would extend to DNA. Mitochondrial DNA (mtDNA) was chosen because of its presence at a known site of free radical formation, its sensitivity and ease of assay, and its known lack of any repair systems. In model experiments we utilized endonuclease III or piperidine to amplify topological form conversions in mtDNA damaged by in vitro reactions with hydroxyl radical. We then applied the amplified detection assays to dog brain mtDNA isolated after 2 or 8 h of reperfusion following a 20-min cardiac arrest. We found that ischemia and reperfusion caused no topological form conversions in mtDNA. Similarly, nucleotide incorporation by a gap-filling reaction showed no sensitivity to digestion of the mtDNA by exonuclease III, an enzyme known to remove blocked 3' termini at the site of radical-generated nicks. Furthermore, the recovery of mtDNA was similar in all experimental groups, suggesting that putatively damaged forms had not been removed by rapid degradation. Thus, despite mitochondrial membrane damage, brain mtDNA does not accumulate oxygen radical damage during postischemic brain reperfusion.
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PMID:Brain mitochondrial DNA is not damaged by prolonged cardiac arrest or reperfusion. 156 Feb 28

Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (O2-) to a highly reactive and cytotoxic hydroxyl radical (OH.). In the present study, we have examined the generation of OH. and free iron in reperfused hearts following either normothermic (37 degrees C) or hypothermic ischemia (5 degrees C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 min at 37 degrees C or 5 degrees C and were then reperfused for 15 min at 37 degrees C. The results of the study suggest that both the OH. generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5 degrees C as compared to 37 degrees C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated O2- at 5 degrees C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH. and free iron as compared to 37 degrees C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH. and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals.
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PMID:Reduced free radical generation during reperfusion of hypothermically arrested hearts. 158 48

Renal levels of glutathione are markedly decreased during periods of renal ischemia due to catabolism to cysteine. We previously demonstrated that cysteine accumulates in the tissue as the thiol during ischemia, and resumption of blood flow causes a transient elevation of cysteine levels in the renal venous effluent and return of tissue cysteine levels to control values. In this study, the oxidation state of renal venous cyst(e)ine was determined. Although cysteine accumulated as the reduced thiol during ischemia, cysteine released into the renal vein upon blood reflow was found to be almost entirely in the disulfide form. To distinguish between oxidation of arterial cysteine and renal cysteine formed from ischemia-induced reduced glutathione (GSH) catabolism, a labeling procedure was developed to label kidney GSH with 35S without significant labeling of arterial plasma cyst(e)ine. With this procedure, the source of oxidized cysteine that appeared in the renal venous plasma after ischemia was identified as resulting from renal GSH catabolism. The data indicate that a rapid oxidative process occurs during the initial period of blood reflow to the postischemic kidney. After 35 min of ischemia, 3 mumol cysteine/g dry wt were released from the kidney and oxidized. Cysteine oxidation is also expected to generate oxygen-centered free radicals. Pretreatment of animals with deferoxamine, a iron chelator, was without effect on the relative amount of venous cysteine in the oxidized form, arguing against a role for free iron in this oxidative process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cysteine oxidation by the postischemic rat kidney. 159 Apr 23

For the etiology of certain inner ear diseases e.g. sudden hearing loss, an impaired cochlear blood flow is discussed. The model of the ferromagnetic thrombosis is an atraumatic method to produce a selective ischemia of the inner ear. The measurement of the inner ear potentials EP, MP and CAP can help to elucidate which inner ear structures are primarily impaired by local ischemia. During the action of a magnetic field to the right cochlea an intravenous injection of small iron particles leads to a thrombosis of the cochlear veins. EP, MP and CAP were measured in the thrombosed ear and MP and CAP in the undisturbed contralateral ear. The methods of microsurgery on the middle and inner ear, the electrophysiological measurement techniques of the inner ear potentials and the method of producing a ferromagnetic thrombosis are described in detail.
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PMID:[Experimental studies of ischemia of the cochlea. Part 1: Method]. 159 19

Extracellular free radicals were detected in rat striatal perfusate samples by intracerebral microdialysis coupled to the spin trapping technique. Five Sprague-Dawley rats were subjected to 30 min of global ischemia followed by reperfusion; throughout the experimental period the intrastriatal dialysing probe was perfused with Ringer's solution containing the spin trap agent pyridyl-N-oxide-t-butylnitrone (100 mM) together with the iron chelating agent diethylentriaminepentacetic acid (100 microM). A radical adduct occurred during ischemia and early reperfusion, but not in basal conditions; the spin adduct was characterized as a carbon centered radical, consistent with the presence of an oxidative attack on membrane lipids. The direct evidence of the formation of free radicals supports the hypothesis that free radicals play a role in the pathogenesis of the histological damage during brain ischemia.
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PMID:Detection of free radicals during brain ischemia and reperfusion by spin trapping and microdialysis. 160 39

Magnetic resonance (MR) images obtained in 15 patients with delayed encephalopathy after acute carbon monoxide (CO) intoxication were reviewed. Images had been obtained 4-9 weeks after exposure to CO, during the relapse of neuropsychiatric symptoms after initial recovery. Bilateral symmetric confluent high signal intensity in the periventricular white matter and centrum semiovale was seen on long-repetition-time images (n = 15). The high intensity extended into the corpus callosum (n = 11), subcortical U fibers (n = 12), and external (n = 9) and internal (n = 7) capsules. Bilateral diffuse low-intensity signal in the thalamus and putamen on T2-weighted images, suggesting iron deposition, was demonstrated in 10 patients. Bilateral ischemia or necrosis of the globus pallidus was seen in nine patients. In three of four patients with follow-up MR imaging studies, a decrease in extent and signal intensity of white matter lesions accompanied lessening of clinical symptoms. These results suggest that the main pathologic feature of delayed encephalopathy associated with CO intoxication is a reversible demyelinating process of the cerebral white matter.
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PMID:Delayed encephalopathy after acute carbon monoxide intoxication: MR imaging features and distribution of cerebral white matter lesions. 160 67

Age-related differences in susceptibility to ischemia/reperfusion injury and the response to the iron chelator deferoxamine during reperfusion were studied in isolated nonworking rabbit hearts subjected to 30 or 40 minutes of ischemia at 37 degrees C followed by 30 minutes of reperfusion. In the experimental group, hearts received a bolus of deferoxamine just before the moment of reflow, followed by a continuous infusion during the first 10 minutes of reperfusion. Isovolumic systolic (peak developed pressure) and diastolic (diastolic pressure versus balloon volume relationship) function was assessed with an intracavity balloon and incremental volume changes. In separate groups of hearts, adenine nucleotide content (adenosine triphosphate, diphosphate, and monophosphate) was measured before ischemia, at end-ischemia, and 30 minutes after reperfusion. The cardiac function measurements showed that after 30 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts recovered to 89% +/- 5% of preischemic levels; this recovery was significantly better than that of adult hearts, which exhibited 67% +/- 6% (p less than 0.01) recovery. Deferoxamine significantly improved cardiac function only in adult hearts (p less than 0.01). However, after 40 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts was reduced to 61% +/- 3% and was not significantly better than that of adult hearts (54% +/- 5%). Deferoxamine significantly improved systolic function in both newborn and adult hearts (p less than 0.01) exposed to 40 minutes of ischemia. Myocardial adenosine triphosphate content fell markedly by the end of 30 and 40 minutes of ischemia in both groups. After 30 minutes of ischemia, newborn but not adult hearts were able to completely recover adenosine triphosphate content by 30 minutes of reperfusion. This advantage was lost after 40 minutes of ischemia. Deferoxamine had no effect on recovery of adenosine triphosphate content in any group. We conclude that (1) newborn hearts recover postischemic function and metabolism faster than adult hearts after shorter periods of ischemia; (2) this advantage is lost as the ischemic period is prolonged; (3) deferoxamine improved postischemic cardiac function after longer ischemic periods, in both age groups, but failed to improve the recovery of myocardial adenosine triphosphate content.
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PMID:Age-related differences in cardiac susceptibility to ischemia/reperfusion injury. Response to deferoxamine. 161 3

Selective interruption of cochlear blood flow is possible without operative manipulations in the middle or inner ear. By fitting a magnet into the external auditory canal and injecting iron filings into the cephalic vein is it possible to obtain an impaired inner ear in otherwise healthy experimental animals that can be kept alive for any length of time. The hearing loss induced by the ischemia normally remains unchanged over a period of weeks. The highly vascularised areas of the cochlea, namely the spiral ligament, the vascular stria, the spiral prominence and the root cells in the external spiral sulcus, as well as the spiral limbus were all clearly degenerated, but to different degrees. Pronounced vacuolisation of cells, degeneration of tissue, reduction of cellular elements, stasis in large and small blood vessels and morphological disorganisation were observed. The organ of Corti showed no changes worthy of note. On revascularisation of the spiral ligament and the spiral limbus with resumption of function, the organ of Corti can return to normal activity again. Repeat blood flow disturbances can also lead to recurrent sudden hearing loss and intermittent loss of hearing.
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PMID:[Experimental studies of ischemia of the cochlea. Part 3: Pathophysiology]. 161 48


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