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)

Among 20 patients with symptoms of cerebrovascular insufficiency, dissociation between memory disturbances and cognitive functions, and PEG studies, there were 13 cases showing atrophy of the hippocampus. The neurological and psychological studies included memory functions tests, IQ, and the analysis of language and praxia. Complementary tests included standard EEG records, EEGs obtained with nasopharingeal electrodes and PEG tomography with selective filling of both temporal horns, in order to demonstrate the inner and lower surface of the temporal lobes. The volume of the Ammon horn was reduced in 13 cases. Hippocampal atrophy was unilateral in 11 patients and bilateral in 2. The fact that hippocampal atrophy was demonstrated by PEG studies in 13 out of 20 cases, appears to be highly significant. This clinico-neuroradiological correlation seems to indicate that hippocampal atrophy, following ischemia in the deep distal vertebro-basilar-posterior cerebral territory, disturbs the function of axial structures (Papez circuit or limbic system) apparently leading to the disturbances of memory functions observed in this group of patients.
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PMID:[Atrophy of the hippocampus of vascular origin. Clinico-pneumoencephalographic study]. 58 22

The isolated blood-perfused rabbit heart, subjected to 60 min of cardioplegic arrest and 60 min of reperfusion, was used to assess the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) on postischemic recovery of left ventricular developed pressure (LVDP), the tissue activity of SOD, and tissue redox state. The five groups studied were the following: PEG-SOD-free control (group A), PEG-SOD as a pretreatment and as an additive during cardioplegia and reperfusion (group B), PEG-SOD as a pretreatment and a cardioplegic additive (group C), PEG-SOD in cardioplegia alone (group D), and PEG-SOD in reperfusion alone (group E). The results show that pretreatment with PEG-SOD improves postischemic recovery of LVDP (72 +/- 2% and 66 +/- 7 vs. 47 +/- 4% in groups B, C, and A, respectively). This protection was associated with an improved tissue redox state. Thus the ischemia-induced rise in oxidized glutathione was reduced from 313 +/- 26% (group A) to 162 +/- 15 and 138 +/- 14% (groups B and C, respectively), and the fall in reduced glutathione was attenuated from 51 +/- 5% to 35 +/- 6 and 13 +/- 5%, respectively. Tissue Mn-SOD activity was also conserved from 36 +/- 4% (group A) to 71 +/- 6 and 94 +/- 4% (groups B and C, respectively). No significant effect was seen when PEG-SOD was applied in cardioplegia or during reperfusion alone.
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PMID:PEG-SOD improves postischemic functional recovery and antioxidant status in blood-perfused rabbit hearts. 141 72

We have previously shown that the polyethylene glycol conjugated superoxide dismutase (SOD), which has a plasma half-life of more than 24 h, protects the blood perfused rabbit heart against injury during ischaemia and reperfusion. However, the profile for the dose-dependency of protection was bell-shaped with loss of efficacy below 6000 and above 30,000 U/kg. In the present study, isolated rabbit hearts, perfused with blood from support rabbits, were subjected to a 2 min infusion with St Thomas' Hospital cardioplegic solution followed by 60 min of global ischaemia (37 degrees C) and 60 min of reperfusion. PEG-SOD was administered 1 h or 12-24 h before ischaemia. We assessed the effect of PEG-SOD on ischaemia- and reperfusion-induced changes in: (i) the tissue content of reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) and (ii) the activity of CuZn-SOD, Mn-SOD and glutathione peroxidase and reductase (GPD and GRD). Ischaemia and reperfusion reduced tissue GSH content by 70% and increased GSSG content by 400% (from their fresh aerobic values of 13.1.9 and 0.09 +/- 0.01 nmol/mg protein, respectively). PEG-SOD, given intravenously at various doses to donor and support rabbits 1 h or 12-24 h before ischaemia, protected against these changes with a bell-shaped dose-response relationship. Thus, with 0, 3000, 6000, 12,000, 30,000 and 60,000 U/kg, GSH content was 4.1 +/- 0.4, 4.8 +/- 0.4, 8.5 +/- 0.5, 12.3 +/- 1.6, 12.3 +/- 1.6 and 5.0 +/- 0.5 nmol/mg protein in the 1 h pretreatment group and 4.1 +/- 0.4, 4.2 +/- 0.5, 10.4 +/- 1.5, 11.2 +/- 1.1, 11.4 +/- 0.7 and 4.7 +/- 0.6 nmol/mg protein in the 12-24 h pretreatment group (means +/- S.E.M.). For GSSG the corresponding values were 0.36 +/- 0.04, 0.34 +/- 0.03, 0.12 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.41 +/- 0.03 nmol/mg protein for the 1 h group and 0.36 +/- 0.04, 0.35 +/- 0.02, 0.15 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.34 +/- 0.02 nmol/mg protein for the 12-24 h group. Ischaemia and reperfusion had no effect on tissue MDA content or CuZn-SOD, GDP and GRD activity, and in general, PEG-SOD also lacked significant effect on any of these variables at any dose studied. However, Mn-SOD activity was severely reduced by ischaemia and reperfusion (from 42 +/- 7 U/mg protein in fresh aerobic controls to 6 +/- 1 U/mg protein at the end of reperfusion).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:PEG-SOD and myocardial antioxidant status during ischaemia and reperfusion: dose-response studies in the isolated blood perfused rabbit heart. 143 18

Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.
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PMID:Polyethylene glycol-conjugated superoxide dismutase attenuates reperfusion injury when administered twenty-four hours before ischemia. 145 23

Intestinal ischemia was induced and maintained for 60 minutes in male Sprague-Dawley rats weighing 175 to 225 g. Prior to reperfusion, the following drugs were administered via the caudal vena cava: 0.9% NaCl (0.5 ml), superoxide dismutase (SOD; 1,000 IU/kg of body weight), polyethylene glycol-conjugated SOD (PEG-SOD; 1,000 IU/kg), or the 21-aminosteroids, U74006F (3 mg/kg) or U78715G (3 mg/kg). A sham-operated control group was included. Animals from each group were euthanatized at 5 periods of reperfusion: 5 minutes, 30 minutes, 18 hours, 3 days, and 7 days after reperfusion. Fixed tissues were embedded in paraffin, sectioned at 5 microns, and stained with H&E. Villi profiled in cross section were measured from the crypt villus junction to the tip of the villus. The mean villus height for each rat was calculated and compared by two-way ANOVA to determine the effects of time and treatment. Villus height was maintained after 30 minutes of reperfusion in rats of the sham- and U74006F-treated groups; U78715G and SOD treatment attenuated the loss in villus height, and villus height was not maintained in the PEG-SOD- and 0.9% NaCl-treated rats. In all rats, villus height was comparable to, or was greater than villus height in sham-operated controls by 18 hours after reperfusion in all animals and remained constant through 7 days. Administration of the 21-aminosteroids maintained villus height after ischemia and reperfusion. Treatment with PEG-SOD did not maintain villus height to the degree observed in rats treated with SOD.
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PMID:Evaluation of intestinal villus height in rats after ischemia and reperfusion by administration of superoxide dismutase, polyethylene glycol-conjugated superoxide dismutase, and two 21-aminosteroids. 146 14

We tested the hypothesis that superoxide dismutase (SOD) conjugated with polyethylene glycol (PEG-SOD) would alter hyperemia following complete global cerebral ischemia. Thirty minutes before ischemia pentobarbital-anesthetized piglets were assigned to receive 3 ml of either PEG-SOD (10,000 U/ml; n = 10), an equivalent concentration of PEG (n = 10), or saline (n = 10) in a randomized and blinded manner. Cerebral ischemia was sustained for 10 min by cross-clamping the ascending aorta. Measurements of cerebral blood flow (radiolabeled microspheres) and oxygen consumption were made before ischemia and at 2, 4, 8, 12, and 15 min of reperfusion. Plasma SOD activity was higher in PEG-SOD-treated piglets (134 +/- 8 U/ml) than in PEG or saline-treated piglets (less than 5 U/ml). All groups and all brain regions demonstrated postischemic hyperemia. There were no differences in blood flow between groups at any time point in any region. At 2 min of reperfusion, blood flow to cerebrum rose from 31 +/- 4 to 88 +/- 9 ml.min-1.100 g-1 (saline), 44 +/- 6 to 102 +/- 17 ml.min-1.100 g-1 (PEG), and 31 +/- 3 to 83 +/- 16 ml.min-1.100 g-1 (PEG-SOD). During reperfusion cerebral oxygen consumption was not different from preischemic values in any group. In conclusion, we demonstrated that exogenously administered PEG-SOD raises serum SOD activity but does not alter the patterns of early cerebral blood flow or metabolic recovery after 10 min of complete global cerebral ischemia in piglets.
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PMID:Polyethylene glycol-conjugated superoxide dismutase fails to blunt postischemic reactive hyperemia. 187 80

The purpose of this study was to assess the protective effects of allopurinol, a blocker of free oxygen radical (FOR) formation, and superoxide dismutase-polyethylene glycol (SOD-PEG), a scavenger of FORs, on ischemic and reperfusion-induced cochlear damage. Fifteen Wistar Kyoto rats (WKY) were randomly assigned to three groups: (1) a control group (5 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion as documented by laser Doppler flowmetry; (2) a drug-treated group (5 animals) that received allopurinol before ischemia/reperfusion; and (3) a drug-treated group (5 animals) that received SOD-PEG before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) of the cochlea was abolished, and the cochlear microphonic (CM) was reduced after ischemia. In contrast, both allopurinol and SOD-PEG-treated animals showed post-reperfusion sensitivity in CAP and CM measures. We interpret these results to indicate that damage to the cochlear from ischemia and subsequent reperfusion can be attenuated by pretreatment with allopurinol or SOD-PEG. This provides indirect evidence that FORs may be partially responsible for cochlear damage resulting from ischemic conditions.
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PMID:The protective effects of allopurinol and superoxide dismutase-polyethylene glycol on ischemic and reperfusion-induced cochlear damage. 194 35

Histologic alterations of ischemia- and reperfusion-induced retinal damage are critically dependent on the duration of the period of ischemia. Male Sprague Dawley rats were anesthetized, and a suture was placed behind the globe including the central retinal artery. Because it was desirable that untreated eyes show a great histologic change due to reperfusion-induced damage (in order that maximum scope would exist for demonstration of any protective effect of a drug treatment), a preliminary series of studies established the time-induced characteristics for the retina with transient regional ischemia. Eyes (n = 6-12 in each group) were subjected to 30, 60, or 90 min of ischemia followed by 0.5, 1, 2, 4, and 24 hr of reperfusion, respectively. The 30-min ischemia followed by reperfusion did not result in any histologic changes; 60-min ischemia followed by reperfusion induced a moderate retinal edema which returned to the preischemic value after 24 hr of reperfusion. The 90-min ischemia followed by reperfusion further aggravated retinal edema and increased the migration of neutrophil leukocytes. Even after 24 hr of reperfusion, the retinal edema had not disappeared although an attenuation was observed. In this study, the rats were treated with superoxide dismutase (SOD-PEG, 15 x 10(3) U/kg) or EGB 761 (100 mg/kg) for 10 days (chronic treatment). The SOD and EGB 761 significantly reduced the development of reperfusion-induced retinal edema and significantly prevented the neutrophil leukocyte infiltration. Both also had a protective effect against reperfusion-induced injury when these agents were administered just before reperfusion ("late" administration).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemia and reperfusion-induced histologic changes in the rat retina. Demonstration of a free radical-mediated mechanism. 201 29

Paraplegia after thoracic aortic aneurysm repair has an incidence of 2.2% to 24%. Oxygen-derived free radicals after reperfusion of an ischemic spinal cord may be partly responsible for neuronal destruction. We studied the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), a free radical scavenger, as a way of increasing spinal cord tolerance to ischemia. Thirty rabbits underwent 40 minutes of aortic occlusion (a known model of paraplegia). Ten of these animals received 25,000 U/kg of PEG-SOD 24 hours before aortic occlusion and two additional doses of 10,000 U/kg, one before and one subsequent to spinal ischemia. Ten animals received superoxide dismutase in the same dosages as those receiving PEG-SOD. Ten control animals received placebo. All animals were studied for 96 hours, at which time a final neurological examination was performed and the results were recorded. Of the 10 animals treated with PEG-SOD, 2 were completely paralyzed whereas 8 had less (7) or no (1) neurological impairment. Eight of the 10 control animals and 9 of the 10 animals receiving superoxide dismutase were completely paralyzed. None of the control animals or animals receiving superoxide dismutase had a normal neurological examination (p less than or equal to 0.05). Treatment with PEG-SOD before and during occlusion increased the rabbit spinal cord tolerance to a 40-minute ischemic insult. Scavenging free radicals may lessen experimental spinal cord injury.
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PMID:Reducing postischemic paraplegia using conjugated superoxide dismutase. 203 20

Oxygen derived free radicals have been shown to be generated during reperfusion of ischemic myocardium by a variety of approaches including spin trap probes. Three levels of injury have been described for the reperfused heart. Periods of ischemia of only several minutes can trigger lethal arrhythmias on reperfusion. Anti-oxidants including SOD and or catalase, as well as iron chelators reduce the incidence of these arrhythmias in both dog and rat. Xanthine oxidase inhibitors are equipotent with SOD in this model suggesting that xanthine oxidase is the source of the radicals. Periods of occlusion lasting 10-15 minutes produce a recoverable defect in contractility termed "stunning". SOD plus catalase has been shown to reduce the incidence of stunning in a variety of models including the xanthine oxidase deficient rabbit. Neither agent on its own seemed to be effective against stunning in either the rabbit or the dog. Stunning is more difficult to demonstrate in the rabbit heart, presumably due to its lack of xanthine oxidase. Periods of ischemia in excess of 20 minutes will result in some irreversible cell death (infarction) with reperfusion. While studies using histochemical methods suggesting that SOD plus catalase given at the time of reperfusion could limit necrosis in the dog model, histological studies reveal that infarct size was not modified but rather, SOD appears to interfere with the ability of tetrazolium to histochemically discriminate between living and dead cells. While PEG SOD with its extended plasma half life was reported to reduce infarct size in the dog, it was unable to protect the reperfused rabbit heart. To date, none of the scavengers have been proven to limit infarction suggesting that free radicals contribute to arrhythmias and stunning, but do not kill cells in the reperfused heart.
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PMID:Superoxide dismutase therapy for myocardial ischemia. 206 Aug 42


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