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

The clinical significance and applicability of interventions aimed at reducing reperfusion injury in postischemic skeletal muscle remain unproven, since long-term muscle salvage has not been demonstrated by most treatment protocols that attenuate early reperfusion injury. We have shown that reperfusion of ischemic skeletal muscle results in an early and prolonged sequestration of white blood cells and activation of the alternative complement cascade. The purpose of this study was to determine if 40 minutes of reperfusion with blood depleted of white blood cells and complement proteins, followed by 2 days of normal perfusion, would reduce muscle necrosis after 5 hours of ischemia. The isolated paired canine gracilis muscle model was used. The treatment muscle was initially reperfused with arterial blood that had been spun, washed, passed through a leukocyte removal filter, and resuspended in hydroxyethyl starch (greater than 99.9% removal of white blood cells and the complement proteins factor B and C4). The contralateral control muscle was subjected to unaltered reperfusion. Blood flow (ml/min/100 gm) was measured by timed collection of gracilis venous blood. Myeloperoxidase activity (absorbance at 655 nm/min/mg tissue protein) in muscle biopsies was used to monitor white blood cell sequestration. After 48 hours of reperfusion in vivo, necrosis was quantified by nitroblue tetrazolium staining. Initial reperfusion with white blood cell and complement depleted blood significantly reduced muscle necrosis (53% +/- 3% vs 29% +/- 8%, p less than 0.0025, paired t test). Early blood flow was improved, (p = 0.0025, repeated measure-ANOVA), but subsequent white blood cell sequestration was not altered (p = 0.33, repeated measure-ANOVA). This suggests that a significant amount of white blood cell mediated injury occurs during the first 40 minutes of reperfusion. Preventing early complement activation and white blood cell mediated reperfusion injury is an intervention that is feasible during surgery and may result in clinically significant salvage of postischemic skeletal muscle.
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PMID:A clinically applicable method for long-term salvage of postischemic skeletal muscle. 184 14

Free-radical reactions, known to occur in the reperfused brain, damage DNA in vitro. We therefore examined the hypothesis that thymine glycols and thymine dimers, which are known to block transcription and are formed by free radical mechanisms, are formed in brain DNA during reoxygenation following ischemia. Such biochemical lesions could account for the failure of protein synthesis that occurs following an ischemic insult. Large dogs were anesthetized, instrumented, and divided into four groups: (1) non-ischemic controls; (2) 20-min cardiac arrest without resuscitation; (3) 20-min cardiac arrest, resuscitation and 2 h reperfusion; and (4) 20-min cardiac arrest, resuscitation and 8 h reperfusion. Genomic DNA was isolated from the cerebral cortex. Thymine glycols were labeled by reduction with [3H]NaBH4. Pyrimidine dimers were determined by ELISA using antibody prepared against ultraviolet irradiated DNA. The data was evaluated by Kruskal-Wallis ANOVA with alpha = 0.05. The rabbit antibodies detected the thymine dimer content in 10 pg UV irradiated DNA but did not react with normal DNA. Borohydride labeling qualitatively detected thymine glycols generated by treatment of DNA with osmium tetroxide. There was no difference between the DNAs from the experimental groups in the content of thymine glycols or pyrimidine dimers (P = 0.608 and P = 0.219, respectively). We conclude that significant quantities of thymine glycols and thymine dimers are not formed in brain DNA during post-ischemic reperfusion. Therefore, the inhibition of brain protein synthesis during reperfusion, observed by other investigators, is unlikely to be caused by interruption of transcription by these species.
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PMID:Thymine glycols and pyrimidine dimers in brain DNA during post-ischemic reperfusion. 185 64

The most effective means to prepare the hepatic donor liver for harvest, preservation, and transplantation are not known. Studies have shown that in combination with an injury to the liver, fasting reduces hepatic function. This study randomized 20 market pigs, 20 to 45 kg, to an overnight fast (fed group) or a 42-hour fast (fasted group). Under general anesthetic perfusion of the portal vein and hepatic artery were controlled. Studies were performed at high flow (30 ml/min/kg portal flow and 10 ml/min/kg arterial flow) and after a 90-minute period of warm ischemia (no flow). Flow was restored at 25% of the original (low flow), then increased to 50% of the original (medium flow). After the ischemic insult, the fed group improved hepatic oxygen consumption at a faster rate than the fasted group (p less than 0.05 by ANOVA). In addition, significant differences were noted between the fed and fasted groups in the amount of insulin delivered by the portal venous system to the liver (p less than 0.001 by ANOVA). Hepatic oxygen consumption was related to insulin delivery (r2 = 0.46; p less than 0.001) for both groups. The data suggest that acute changes in the nutritional status of both the donor and the recipient may affect hepatic recovery from ischemia.
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PMID:Fasted state impedes recovery of porcine hepatic oxygen consumption after warm hepatic ischemia. 192 63

Hypothermic storage of cardiac allografts is routinely used for transplantation but is associated with an increased mortality when ischemic times are greater than 4 hours. The ideal storage conditions (solution and temperature) could extend the current limits of cold ischemia. Human endothelial cells and ventricular myocytes were studied to screen various solutions and temperatures for organ preservation. Four solutions (modified Euro-Collins, phosphate-buffered saline, Stanford cardioplegia, and University of Wisconsin) were evaluated. Endothelial cells were evaluated after prolonged hypothermic storage consisting of 0 degree, 4 degrees, and 8 degrees C for 36 hours, and ventricular myocytes were stored at 0 degree and 8 degrees C for 24 hours. Cell viability was determined by morphology (10 dishes per group), and trypan blue exclusion (5 dishes per group) in addition to a cell adhesion assay (endothelial cells 5 dishes per group) and adenine nucleotide analysis with high-performance liquid chromatography techniques (ventricular myocytes 5 dishes per group). Endothelial cell morphology was best preserved by University of Wisconsin solution (p less than 0.001, chi 2) and at 0 degree C (p less than 0.01, chi 2). Endothelial cells stored with University of Wisconsin solution excluded trypan blue better (1.0% +/- 0.5% cells stained, p less than 0.001. Analysis of variance [ANOVA]). Cell adhesion was poorly protected with Stanford cardioplegia (p less than 0.001, ANOVA). Myocyte morphology was preserved best with University of Wisconsin solution at 0 degree C (p less than 0.001, chi 2). According to trypan blue staining, Euro-Collins and University of Wisconsin solutions were superior to Stanford cardioplegia or phosphate-buffered solutions (p less than 0.001, ANOVA). Temperature did not influence the trypan blue results. Adenosine triphosphate was maintained best with University of Wisconsin solution at 0 degree C (p less than 0.01, ANOVA). Myocytes were more sensitive to the effects of prolonged storage compared with endothelial cells by morphologic criteria and trypan blue staining characteristics, irrespective of the shorter preservation times. University of Wisconsin solution was the most effective solution tested. Colder temperatures (0 degree to 4 degrees C) provided better protection than 8 degrees C. Myocytes were more sensitive to prolonged preservation than endothelial cells. Furthermore, the technique used appears helpful as a model of prolonged hypothermic storage and could be expanded to assess other interventions.
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PMID:Prolonged hypothermic cardiac storage with University of Wisconsin solution. An assessment with human cell cultures. 194 84

The role of PMN in the reperfusion injury after ischemia is unclear. It was the purpose of this study to determine if PMN functions of phagocytosis and chemotaxis were altered after a brief period of ischemia (2 hr) followed by reperfusion (1 hr) in a model where no significant reperfusion injury occurred. Baseline blood samples were drawn from an ear artery from New Zealand white rabbits for PMN and serum. The right iliac and femoral arteries were clamped for 2 hr. Just prior to clamp release, blood was harvested from the right iliac vein. After 1 hr of reperfusion, blood was again harvested from the right iliac vein. Phagocytosis was measured by the percentage ingestion of zymosan by PMN. The zymosan beads had been opsonized wtih baseline (b) (b), ischemia (i), or reperfusion (r) serum. Chemotaxis was evaluated by the number of PMN migrating across a filter. Serum obtained from b, i, and r blood samples served as the chemoattractants. Results for phagocytosis demonstrated a significant increase in i and r PMN as compared to b PMN. Opsonization by b,i, or r serum did not enhance this effect (ANOVA, F = 4.477; P = 0.0266). Similar increases in chemotaxis were observed for i and r PMN which also were not enhanced by the chemoattractants of b, i, or r serum (ANOVA, F = 25.43; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophil (PMN) phagocytosis and chemotaxis after 2 hr of ischemia. 205 78

The effect of treatment with the potent, non-competitive NMDA receptor-channel antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d] cyclohepten-5,10-imine maleate (MK-801) on ischemia-induced brain damage was studied in a well-characterized model of focal neocortical infarction in spontaneously hypertensive rats. Anesthesia exposure was minimized to the surgical procedure and the infarcts were allowed to mature over a 24-h period. Pretreatment with 5 mg/kg i.p. MK-801 (n = 11 control, n = 12 treated animals) 30 min before induction of focal cerebral ischemia had no statistically significant influence on infarct volumes. However, pre- and post-treatment with MK-801 5 mg/kg i.p. 30 min before induction of ischemia and 2.5 mg/kg each at 8 and 16 h after onset of ischemia, reduced infarct volumes in two separate studies by 29% (investigator J.T., n = 5 control and n = 7 treated animals) and 20% (investigator U.D., n = 8 control and n = 8 treated animals), respectively. The combined reduction in infarct volume in MK-801-treated animals for both investigators was 23% (P = 0.016, ANOVA). The findings indicate a smaller neuroprotective effect of MK-801 in spontaneously hypertensive rats subjected to focal ischemia than in previous reports using normotensive animals.
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PMID:Pre- and post-treatment with MK-801 but not pretreatment alone reduces neocortical damage after focal cerebral ischemia in the rat. 214 95

The lower extremity may be exposed to prolonged periods of ischemia, resulting in depletion of intracellular energy stores in the affected skeletal muscle. The role of adenine nucleotide reduction and failure of resynthesis on reperfusion in determining the extent of muscle necrosis was investigated in this study, in addition to the possible beneficial effects of the addition of exogenous adenosine triphosphate-magnesium chloride during early reperfusion. The isolated paired canine gracilis muscle model was used. After 4 hours of normothermic ischemia in group I, a perfusate Krebs-Henseleit solution plus the gradual reintroduction of oxygenated blood flow was compared to standard reperfusion. In group II, a similar infusion protocol was used, with the addition of 2 mmol/L adenosine triphosphate-magnesium chloride and compared to normal reperfusion. Adenosine triphosphate-magnesium chloride resulted in the salvage of skeletal muscle, 57% +/- 12% versus 44% +/- 14% (p less than 0.05, n = 6 pairs). Reperfusion with the solution alone increased the resulting necrosis (42% +/- 13% vs 60% +/- 20%, n = 6 pairs). Adenine nucleotide stores were not increased, but oxygen consumption was increased by magnesium chloride-adenosine triphosphate (p less than 0.05, analysis of variance [ANOVA]). A clear relationship was demonstrated between the fall in energy stores, as measured by a change in energy charge potential from preischemia to end ischemia levels, and the extent of resulting necrosis (p less than 0.01). In summary, the addition of 2 mmol/L to an infusion of Krebs-Henseleit solution during reperfusion results in significant salvage of skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exogenous magnesium chloride-adenosine triphosphate administration during reperfusion reduces the extent of necrosis in previously ischemic skeletal muscle. 231 33

The authors retrospectively reviewed the charts of 36 pediatric patients who had undergone cardiac surgery with hypothermic cardiopulmonary bypass (CPB) (n = 24) or profound hypothermia with circulatory arrest (PHCA) (n = 12), none of whom had received dextrose in the clear CPB pump prime, maintenance iv fluids, or cardioplegia solution. The authors studied whether the doses of fentanyl or methylprednisolone, or rates of dextrose infusion from blood products during CPB or from vasoactive infusions in 5% dextrose in water, were correlated with the blood glucose concentrations at the termination of CPB. Because other investigations have indicated that even moderate hyperglycemia during cerebral hypoxia or ischemia may predispose patients to an increased risk of neurologic deficit, the authors wished to determine whether any of these factors might contribute significantly to the elevation in blood glucose commonly seen in these patients. Multiple regression analysis and ANOVA were performed on these data, and a P value of 0.0125 was considered significant. The dose of methylprednisolone, and rates of infusions of dextrose from blood products in the CPB pump prime or from 5% dextrose in water at the termination of CPB did not correlated significantly with the blood glucose level. The dose of fentanyl administered to patients prior to the end of CPB was significantly correlated with the glucose concentration (r2 = 0.416; P = 0.0001). No patient who received greater than or equal to 50 micrograms/kg of fentanyl had a blood glucose concentration of greater than 200 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fentanyl dosage is associated with reduced blood glucose in pediatric patients after hypothermic cardiopulmonary bypass. 233 96

The present study evaluated the ability of DHV-PGE2ME, a topically effective 16-vinyl prostaglandin E2 analogue, to improve the tolerance of skin flaps to a period of ischemia. DHV-PGE2ME and placebo were applied to bilateral island flaps on 70 anesthetized rats; then the vascular pedicle of each flap was clamped for 10 hours. Treated flaps evidenced significantly better reperfusion, as documented by quantification of fluorescein dye delivery at 90 minutes after clamp release, and they had significantly greater ultimate viability (p less than 0.05, by ANOVA). While less than 3 percent of untreated flaps survived, those treated with 1.75 and 17.5 microgram/cm2 of drug evidenced 76 and 86 percent survival, respectively. Treatment of a given flap did not affect its contralateral mate, since there was no evidence of a systemic effect. Especially since its effect can be limited to the site of application, DHV-PGE2ME should be valuable for the treatment of compromised perfusion in a variety of settings.
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PMID:The effects of a topical PGE2 analogue on global flap ischemia in rats. 281 89

A new method for brain resuscitation following acute focal ischemic insult has been developed in this laboratory. The technique utilizes a surrogate route to supply cerebral metabolites and employs highly oxygenated fluorocarbons (OFNS), which are efficient gas transport and exchange agents, perfused through the ventriculo-subarachnoid spaces. We previously described a return of aerobic metabolism and EEG after severe global ischemia by oxygenated perfusions and now report treatment-induced reduction in the size of experienced cerebral infarction. Twenty-eight cats were anesthetized (choralose and urethane), tracheotomized and placed in a stereotactic frame. Physiologic adjustments assured arterial blood pCO2 28-35 Torr, pO2 100-150 Torr pH 7.4 and glucose less than 200 mg%. The left middle cerebral artery was exposed transorbitally and temporarily clipped along with both common carotids for 2 h. One hour later (3 h after ischemic onset) the treated group were perfused by the ventriculo-cisternal route either with OFNS [pO2 = 600 Torr; 3 ml/min 6 h, 2 ml/min 2 h, 1 ml/min 2 h, 0.5 ml/min 2 h at 10 mm Hg intracranial pressure (ICP)] or with the vehicle perfusate. Eighteen to twenty hours after the ischemic insult the animals were sacrificed. Sections of fresh brain of 0.5 mm thickness were incubated in 1% triphenyl tetrazolium chloride. The infarcted areas were confirmed with classic neuropathologic techniques. Areas of infarction (expressed in cm3 and as % of the brain) were measured using a planimeter. OFNS-treated brains contained 80% less infarcted tissue than the vehicle-perfused or untreated stroked animals. The infarcted areas were significantly treatment reduced (P less than 0.05 ANOVA and Bonferroni tests).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Focal cerebral ischemia: reduction in size of infarcts by ventriculo-subarachnoid perfusion with fluorocarbon emulsion. 315 23


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