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 effects of antioxidant drugs on retinal ischemia-reperfusion damage were studied by electroretinograms (ERGs) from reperfused Dutch rabbit eyes. After inducing retinal ischemia by increasing the intraocular pressure (IOP) up to 140 mmHg for 60 minutes, the reperfusion was started by lowering the IOP to the normal level. Mannitol, polyethylene glycol superoxide dismutase (PEG-SOD), or ascorbic acid was administered by drip-infusion to the rabbits immediately after (early group) or 1 hr after (delayed group) the start of reperfusion. Saline, as a control, was administered by the same method as the early group. The a- and b-waves were recorded before the ischemia and during the reperfusion. In the early group treated by each drug, the recovery rates of the b-wave amplitudes at 4 hrs after the start of reperfusion were significantly greater than those in the controls. In the delayed group, the ERG recovery rate in rabbits treated with PEG-SOD was significantly better than in the controls. These results indicated that all these drugs were effective in protecting from the retina from the ischemia-reperfusion damage, and that some antioxidant drugs might be effective even when they were administered after the start of reperfusion.
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PMID:[An electrophysiological study on the effect of antioxidant drugs against retinal ischemia-reperfusion damage]. 778 13

Therapeutic effect of superoxide dismutase (SOD) and three derivatives: a conjugate with polyethylene glycol (SOD-PEG2), a cationized derivative (cSOD), and a mannosylated derivative (Man-SOD), on acute renal failure induced by ischemia/reperfusion was studied in rats. SOD and derivatives were administered intravenously to the rat after nephrectomy of the right kidney and before and after 60 min occlusion of the left renal artery. At 48 hr after reperfusion, the renal function was evaluated by determining the urinary excretion rate of 14C-inulin injected intravenously. No therapeutic effect on the impaired renal function was shown in the case of low dose SOD (2600 unit/kg) treatment. In contrast, administration of cSOD which was shown to be taken up by the isolated perfused kidney from its capillary side and SOD-PEG2 which maintained high plasma concentration exhibited significant therapeutic effect, as did SOD at ten-fold higher dose (26,000 unit/kg). On the other hand, renal damage was promoted by Man-SOD. Thus, the present study demonstrated that chemical modification may improve the therapeutic effect of SOD on the ischemic acute renal failure and increased SOD concentration in the renal vascular space is an important factor for the improved effect.
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PMID:Improvement of therapeutic effect of human recombinant superoxide dismutase on ischemic acute renal failure in the rat via cationization and conjugation with polyethylene glycol. 785 57

Cell damage initiated during ischemia, as a result of oxygen depletion, continues during reperfusion, and recovery is dependent on the length of the ischemic period. This study investigates the effect of polyethylene glycol-modified hemoglobin (PEG-Hb) on recovery of tissue oxygen tension after induced ischemia.
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PMID:Normal oxygen tension restored in the ischemic rat liver model by PEG-hemoglobin. 799 3

We performed the present study to clarify whether lecithinized superoxide dismutase (PC-SOD) enhanced its pharmacologic potency by increasing its cell membrane affinity. PC-SOD, in which 4 molecules of a phosphatidylcholine (PC) derivative were covalently bound to each dimer of recombinant human CuZn-SOD (rhCuZn-SOD), was shown to have a high membrane affinity using a laser confocal imaging technique. PC-SOD efficiently scavenged superoxide anion (O2-) produced by phorbol myristate acetate (PMA)-stimulated human neutrophils (IC50 0.60 U/ml), and it exerted a dose-dependent scavenging effect (IC50 1.27 U/ml) even when the neutrophils were washed after incubation with PC-SOD. In contrast, neither unmodified SOD nor polyethylene glycol-bound SOD (PEG-SOD) showed a scavenging effect for washed neutrophils, even at a high concentration (100 U/ml). PC-SOD also showed a strong protective effect against human vascular endothelial cell damage caused by O2- generated by stimulated neutrophils, and PC-SOD was approximately 100-fold more potent than unmodified SOD (in vitro IC50 100 U/ml for PC-SOD and > 10,000 U/ml for unmodified SOD). Moreover, PC-SOD (50,000 U/kg) had an inhibitory effect on ischemia-reperfusion paw edema in mice, whereas neither unmodified SOD nor PEG-SOD had any effect. These results suggest that PC-SOD (designed to target for cell membranes) exerted a far higher pharmacologic activity by increasing cell membrane affinity than unmodified SOD and may be potentially useful for various clinical applications.
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PMID:Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. 799 83

Kidney preservation under mild hypothermic conditions (24 degrees C) was performed to preserve organs for a long time, to determine the viability of damaged organs, and to evaluate the viability of organs that have previously been stored in cold solution. Rabbit kidneys were perfused via the renal arteries. The perfusate was composed of glucose, allopurinol, PEG-SOD, adenosine, dexamethasone, insulin, HES and FC-43. This solution was an attempt to simulate the electrolyte constitution of extracellular fluid (pH 7.40 delta pH). The functions of all groups of kidneys were evaluated by measuring urine output, urine pH and urine electrolytes. The suitable perfusion pressure was 80 mmHg. The kidneys without a warm ischemic period were well stored and functioned for over 12 hours under 24 degrees C perfusion. In the warm ischemic groups, the viability and histological structure of the kidneys were well maintained and conditioned for 12 hours at up to 35 min of warm ischemia. The kidneys which were stored in 4 degrees C UW-solution for 24 hours had a good urination using mild hypothermic perfusion for 12 hours. This suggest that mild hypothermic perfusion will become a useful method for preserving the condition of organs and for determining and evaluating the viability of organs that have previously been stored in cold solution.
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PMID:[Experimental studies on functional preservation, conditioning and evaluation of the viability of rabbit kidneys utilizing mild hypothermic perfusion]. 805 26

The aim of this study was to optimize the properties of a lubricious bioerodible hydrogel barrier for the prevention of postoperative adhesions. Water-soluble macromers based on block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) or poly(glycolic acid) with terminal acrylate groups were used, and these macromers were gelled in vivo by exposure to long wavelength ultraviolet light. The precursor was photopolymerized from buffered saline solution while in contact with the tissues. This resulted in the conformal coating of the tissue with an adherent hydrogel film, while forming a nonadhesive barrier at the free surface, on the treated wound site. The hydrogels were evaluated in two animal models of postsurgical adhesions, first in a rat cecum abrasion model and then in a rabbit uterine horn ischemia model. In the rat cecum model, six of seven animals treated with a hydrogel, with glycolide in the precursor as the comonomer, showed no adhesions; untreated animals and animals treated with precursor, but not gelled with light, showed consistent dense adhesions. In the rabbit uterine horn ischemia model, using hydrogels with lactide in the precursor as the comonomer, and PEG of molecular weight from 6,000 to 18,500 Da, adhesions were dramatically reduced, with occurrence in none of seven animals treated with a gel containing PEG 10,000. By contrast, the seven animals in the control group demonstrated a mean of 35% involvement of the horn length in dense, fibrous adhesions. These materials, photopolymerized in vivo in direct contact with the tissues, appear to form an adherent hydrogel barrier that is highly effective in reducing postoperative adhesions in the models used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention. 808 51

We tested the hypothesis that administering polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the time of reperfusion would alter recovery of cerebral blood flow (CBF; microspheres) response to alteration in arterial PCO2 in pentobarbital-anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after ischemia (10 min aortic cross clamp). To determine the effect of preischemic versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a randomized, blinded fashion before ischemia and just before reperfusion. Cerebral oxygen consumption and somatosensory evoked potentials were measured during reperfusion as an assessment of brain function. During reperfusion, no group demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not different from preischemic values with either preischemic or postischemic PEG-SOD treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not attributable to improved postischemic cerebral oxygen consumption. Somatosensory evoked potential amplitude was decreased similarly during reperfusion (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyethylene glycol-conjugated superoxide dismutase improves recovery of postischemic hypercapnic cerebral blood flow in piglets. 825 89

Generation of free radicals during reperfusion after organ ischemia has been implicated in the pathogenesis of ischemic injury. We have previously shown that a combination of intravenous polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT), at a dose of 10,000 U/kg each, is effective in reducing infarct size in a focal cerebral ischemia model in the rat. It is not clear whether PEG-SOD alone is sufficient to reduce ischemic brain injury. In this study we determined the therapeutic efficacy of PEG-SOD and its dose-response curve. In a range of 1,000-30,000 U/kg, PEG-SOD exhibited a U-shaped dose-response curve. Only 10,000 U/kg significantly reduced infarct size [control 121 +/- 12 mm3 (mean +/- SE), n = 35; PEG-SOD 95 +/- 10 mm3, n = 36, P < 0.05]. PEG-SOD at the doses tested did not have significant acute hemodynamic effects but had a tendency to improve postischemic hypotension. This beneficial effect of PEG-SOD on blood pressure did not appear to fully account for the treatment effect of PEG-SOD on infarct size. The narrow therapeutic dose range of PEG-SOD in this study and similar findings of SOD in other investigations may contribute to the inconsistent protective effects of SOD preparations in ischemia-reperfusion injury in the literature.
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PMID:Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion. 834 41

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.
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PMID:Superoxide scavengers do not prevent ischemia-induced alteration of cerebral vasodilation in piglets. 838 55

We employed hyperosmotic concentrations of penetrating cryoprotective agents (CPA) to store the isolated rat hearts unfrozen at subzero temperatures. The effect of acute exposure to CPA was assessed by flushing the hearts with CP-14, a cardioplegic solution, containing methanol (MeOH), ethanol (EtOH), ethylene glycol (EG), or propylene glycol (PG) for 2 min and reperfusing immediately with Krebs-Henseleit buffer in a working-heart model. The maximal doses that did not cause irreversible suppression of heart function were: MeOH, 1.78 M; EtOH, 1.27 M; EG, 0.84 M; and PG, 0.87 M. For nonfreezing storage, the hearts were flushed with CP-14 containing the highest tolerable concentrations of MeOH, EtOH, EG, or PG, stored for 6 h at -3.7, -2.8, and -1.4 degrees C, respectively, and then reperfused. Control cardiac output (CO) was 76.2 +/- 1.8 ml/min. Post-reperfusional recovery of CO was 86% in MeOH hearts, 82% in EtOH hearts, 76% in EG hearts, and 79% in PG hearts. Thus MeOH offered not only the least cardiac-suppressing effect but the lowest nonfreezing storage temperature. When storage time was extended, recovery and myocardial ATP level decreased with time in hearts flushed with CP-14 + 1.78 M MeOH and stored at -3.7 degrees C. The decay of function was faster than the decay of ATP level, suggesting energy was better preserved than function. The low return of function, however, may be related to CPA toxicity, osmotic stress, and ischemia/reperfusion injury. Nonfreezing storage at subzero temperatures using these CPAs may provide a novel approach to long-term cardiac preservation.
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PMID:Subzero nonfreezing storage of the mammalian cardiac explant. I. Methanol, ethanol, ethylene glycol, and propylene glycol as colligative cryoprotectants. 840 87


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