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)

Superoxide dismutase (SOD) scavenges oxygen radicals that are implicated in the pathogenesis of intestinal ischemia-reperfusion injury. The effect of intestinal ischemia and reperfusion was investigated in transgenic mice overexpressing human Cu-Zn SOD. Ischemia was induced by occluding the superior mesenteric artery. Myeloperoxidase activity was determined as an index of neutrophil infiltration, and malondialdehyde levels were measured as an indicator of lipid peroxidation. Forty-five minutes of intestinal ischemia followed by 4 h of reperfusion caused an increase in intestinal levels of malondialdehyde in both nontransgenic and transgenic mice, but the concentration of malondialdehyde was significantly greater in nontransgenic mice. Intestinal ischemia-reperfusion also caused an increase in intestinal and pulmonary myeloperoxidase activity in nontransgenic and transgenic mice, but the transgenic mice had significantly lower levels of myeloperoxidase activity than nontransgenic mice. Transgenic mice had higher levels of intestinal SOD activity than nontransgenic mice. There were no significant differences in the catalase or glutathione peroxidase activities. In conclusion, our study demonstrates that the overexpression of SOD protects tissues from neutrophil infiltration and lipid peroxidation during intestinal ischemia-reperfusion.
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PMID:Intestinal ischemia and reperfusion injury in transgenic mice overexpressing copper-zinc superoxide dismutase. 935 55

Ischemia/reperfusion injury (IRI) after free tissue transfer of the small intestine results in transmural tissue damage. This study examined the effects of IRI on the jejunum. Wistar rats served either as controls (N=10) or underwent clamping of the infrarenal aorta for 1 hour followed by 1 hour of reperfusion (N=10). Both ischemia and reperfusion reduced the protein and deoxyribonucleic acid content of the jejunal mucosa (p < 0.05). Myeloperoxidase activity in the jejunal mucosa remained relatively low. The expression of leukocyte function-associated antigen 1 and intercellular adhesion molecule 1 (ICAM-1) on the surface of mucosal cells was not altered significantly by the ischemic insult, but was reduced after the period of reperfusion (p < 0.05). This coincided with an increase in messenger ribonucleic acid (mRNA) for ICAM-1 within isolated mucosal cells (p < 0.05). The specific activity of glutaminase in isolated jejunal mucosal cells was diminished after ischemia and reperfusion (p < 0.05), and this was not associated with an appreciable change in glutaminase mRNA expression. These results have identified some molecular mechanisms underlying IRI of the small intestine that are possible candidates for therapeutic intervention.
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PMID:The influence of ischemia/reperfusion injury on the jejunum. 964 Dec 80

It has been demonstrated that administration of an interleukin-1 receptor antagonist protein (IL-1ra) reduces ischemic brain injury; however, the detrimental mechanism initiated by interleukin-1 (IL-1) in ischemic brain injury is unclear. In this study, we used mice that were transfected to overexpress human IL-1ra to elucidate the role of IL-1 in the activation of the inflammatory response after middle cerebral artery occlusion (MCAO). Myeloperoxidase (MPO) activity and immunohistostaining were used as a marker of polymorphonuclear leukocytes (PMNL) infiltration. Adenoviral vector (1 x 10(9) particles) was administered by injection into the right lateral ventricle in mice. Five days later, MCAO was performed on the mice using a suture technique. Permanent MCAO was achieved for 24 hours in the Ad.RSVIL-1ra-transfected. Ad.RSVlacZ-transfected, and saline (control) mice. Myeloperoxidase activity was quantified in each region and localization of MPO was determined by immunohistochemistry. After 2 hours of MCAO, the surface cerebral blood flow was reduced to 13.5% +/- 3.4%, 10.75% +/- 2.6%, and 10.9% +/- 2.6% of baseline in the ischemic hemisphere in Ad.RSVIL-1ra-transfected, Ad.RSVlacZ-transfected, and saline-treated mice, respectively. The MPO activity in the ischemic hemisphere in the Ad.RSVlacZ group was similar to that in the saline control group (cortex: 0.40 +/- 0.22 versus 0.33 +/- 0.11; basal ganglia: 0.46 +/- 0.23 versus 0.49 +/- 0.17; P > 0.05); however, it was significantly reduced in the Ad.RSVIL-1ra group (cortex: 0.18 +/- 0.07; basal ganglia: 0.26 +/- 0.15; P < 0.05). Myeloperoxidase immunohistochemistry showed that the massive accumulation of MPO-positive cells in the ischemic cortex, striatum, and corpus callosum regions was greatly attenuated in Ad.RSVIL-1ra-transfected mice. Our results indicate that Ad.RSVIL-1ra-transfected mice provide a useful tool to study the mechanism of action of IL-1. The MPO activity assay and immunostaining after 24 hours of focal ischemia were significantly reduced in IL-1ra gene-transfected mice, suggesting that IL-1 may play an important role in the activation of inflammatory cells during focal cerebral ischemia.
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PMID:Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist. 970 45

Nitric oxide (NO) is believed to be identical to endothelium-dependent-relaxing-factor, a potent vasodilator. In addition, NO has been founded to play a critical role in the maintenance of vascular permeability through its attenuation of polymorphonuclear neutrophils (PMN) and platelets. In the present study, we have evaluated the effects of inhaled NO at reperfusion in canine left single-lung allotransplantation from a non-heart-beating donor. Twelve weight-matched pairs of adult mongrel dogs were used. The donor dogs were sacrificed by an intravenous injection of potassium chloride without heparinization. They were left at room temperature for 3 hours. Then, the recipient dogs received a left single-lung allotransplantation. After implantation, the right bronchus and pulmonary artery were ligated. In Group 1 (n = 6), NO gas was administered continuously at a concentration of 40 parts per million throughout a 6-hour assessment period. In Group 2 (n = 6), nitrogen gas was administered in the same manner as NO, for control. The survival time in Group 1 was significantly longer than that in Group 2. The arterial oxygen tension in Group 1 was significantly higher than that in Group 2. The pulmonary vascular resistance was significantly lower in Group 1 than in Group 2. The aortic pressure and the cardiac output each did not differ significantly between the two groups. Myeloperoxidase activity was significantly lower in Group 1 than in Group 2. Inhaled NO at reperfusion is beneficial in lung transplantation from non-heart-beating donors because it attenuates ischemia-reperfusion injury by inhibiting PMN activation and vasodilating pulmonary vasculature.
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PMID:Effects of inhaled nitric oxide in canine lung transplantation from non-heart-beating donor. 978 59

The effect of the platelet activating factor antagonist RP 59227 (Tulopafant) on myocardial infarct size was compared to that of a vehicle-treated control group in barbital-anesthetized dogs subjected to 90 min of left circumflex coronary artery occlusion and 5 h of reperfusion. The myocardial region at risk and infarct size were determined by the triphenyltetrazolium histochemical technique and regional myocardial blood flow by radioactive microspheres. Myeloperoxidase (MPO) activity was used as an index of neutrophil infiltration into the ischemic-reperfused area. Vehicle (n = 11) or RP 59227 (n = 12, 2.5 mg/kg i.v.) were administered 15 min prior to occlusion. Hemodynamics and regional myocardial blood flow in the ischemic-reperfused areas did not differ between the two groups throughout the experiment. In contrast, the number of dogs which developed ventricular fibrillation during occlusion and reperfusion was significantly less in RP 59227-treated dogs (8 of 11 in the control group vs. 3 of 12 in the RP 59227-treated group, p < 0.05). Myocardial infarct size expressed as a percent of the area at risk (control, 39.0 +/- 5.0; RP 59227, 24.8 +/- 3.4%) or as a percent of the left ventricle (control, 15.3 +/- 1.9; RP 59227, 9.0 +/- 1.3%) was significantly smaller in the RP 59227-treated group. Infarct size was inversely related to the collateral blood flow in the inner two thirds of the left ventricular wall of the infarct area, and this relationship was shifted downward in the RP 59227-treated group (p < 0.05). MPO activity in the border zone immediately adjacent to infarcted tissue was reduced in the RP 59227-treated dogs (control, 7.4 +/- 0.5 U/g; RP 59227, 4.1 +/- 0.4 U/g). In additional in vitro studies, the addition of PAF was found to elicit a concentration-dependent potentiation in chemiluminescence produced by purified canine neutrophils, a measure of oxygen-derived free radicals, which was stimulated with a low concentration of opsonized zymosan. Preincubation of neutrophils with RP 59227 resulted in a concentration-dependent decrease in chemiluminescence produced by PAF primed cells. Taken together, these data demonstrate that RP 59227 effectively reduces myocardial infarct size and reduces the incidence of ischemia and reperfusion-induced arrhythmias in barbital-anesthetized dogs, and support the concept that PAF plays an important role in the pathogenesis of acute myocardial infarction.
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PMID:Effect of the platelet-activating factor antagonist RP 59227 (Tulopafant) on myocardial ischemia/reperfusion injury and neutrophil function. 983 48

Monoclonal antibodies to adhesion molecules have been used in many trials to prevent ischemia-reperfusion injury. Sulfatide reacts strongly with P- and L-selectin, which play an important role in the initiation of neutrophil-endothelial interactions occurring in injured or inflamed tissues. The purpose of this study was to evaluate the effect of sulfatide on ischemia-reperfusion injury of the rat skin flap. Sulfatide was administered intravenously just before elevation of the right abdominal epigastric flap. The femoral artery and vein were clamped above and below the epigastric vessels for 10 or 11 h and then the clamp was released. Administration of sulfatide augmented significantly the flap area surviving in the 10-h ischemic model (7.18 +/- 0.47 cm2 versus control 5.15 +/- 0.39 cm2. P = 0.01). In the 11-h ischemic model the area was 4.59 +/- 0. 36 cm2 versus control 1.73 +/- 0.31 cm2 (P = 0.001). The ATP levels in the flap gradually increased after release of the clamp in the rat administered sulfatide, and the increase was significant at 48 h (P = 0.006). Histological examination 48 h after surgery showed greater leukocyte invasion into the control flap than into the flap of the rat administered sulfatide. Myeloperoxidase activity was significantly reduced 48 h after reperfusion in the 11-h ischemic model. This study indicates that sulfatide has a significant protective effect against ischemia and reperfusion in rat epigastric flaps.
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PMID:Sulfatide protects rat skin flaps against ischemia-reperfusion injury. 987 14

The effects of systemic administration of calcitonin gene-related peptide (CGRP) on survival and inflammation of experimental skin flaps subjected to prolonged arterial ischemia were studied. An island groin flap was elevated in the rat. The femoral artery was occluded for 8, 10, 12 or 14 h in four groups of 10 rats. In a group of 10 sham-operated control animals, the femoral artery was not occluded. After ischemia, blood flow was restored and flap survival evaluated at day 7. Following 12 h of ischemia, three flaps (30%) survived, compared with 100% survival of the control group. In the second part of the study the effects of CGRP on flap survival were assessed. Eighty flaps were rendered ischemic for 12 h, and received systemic CGRP (10(-7), 10(-8), 10(-9), 10(-10) M) or saline (control) at the end of the ischemia period. Administration of CGRP (10(-7) M) significantly increased the number of flaps surviving compared with the control. The effect of systemic pretreatment of the animals with the CGRP receptor antagonist CGRP8(-37), followed by CGRP (10(-7) M) treatment was also evaluated in 10 flaps. Flap survival in this group was 10%. In the third part of the study the anti-inflammatory effects of CGRP were evaluated. Forty rats were subjected to arterial ischemia for 12 h, and received systemic CGRP (10(-7) M), or saline at the end of the period of ischemia. The animals were sacrificed at 24 h and flap tissue samples were obtained. Myeloperoxidase (MPO) analysis was used as marker of neutrophil accumulation. CGRP (10(-7) M) significantly reduced the 24 h MPO accumulation in the flap, compared with saline treatment. A group of animals was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant increase of MPO accumulation was seen, compared with the group treated only with CGRP. This study suggests that CGRP has a beneficial effect on survival of the rat ischemic groin flap, and diminishes the inflammatory response to the ischemic insult.
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PMID:Calcitonin gene-related peptide improves skin flap survival and tissue inflammation. 1018 62

The purpose of the present work was to evaluate the kallikrein-kinin system and effects of hypothermia during renal ischemia and reperfusion. Male C57BL/KSJmdb mice were subjected to 20 or 60 min ischemia for different periods of reperfusion. Our results demonstrate that short periods of ischemia followed by reperfusion did not cause significant alterations in kallikrein activity, Evans Blue (EB) extravasation, prokallikreins, myeloperoxidase activity or plasma creatinine concentration. Edema was evident at 1 h reperfusion in the treated mice, but returned to basal values after 24 h reperfusion. Kallikrein activities and EB extravasation showed a significant increase in 60 min ischemic mice. Myeloperoxidase activity in the kidney of the mice confirmed net infiltration in the group with 60 min ischemia and 24 h reperfusion. The generation of kinins and activation of matrix degrading enzymes by tissue kallikrein, liberated from both renal and infiltrated leukocytes, could be responsible at least in part for the damage observed in the kidney of mice subject to 60 min ischemia and reperfusion. The hypothermia significantly reduced the inflammatory process in the 60 min ischemic mice, and did prevent an increase in vascular permeability. Nevertheless, the tissue edema was not shown to change between normothermic and hypothermic ischemic mice.
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PMID:Renal ischemia-induced increase in vascular permeability is limited by hypothermia. 1059 59

Myeloperoxidase (MPO) immunohistochemistry was used to ascertain the role of polymorphonuclear leukocytes in hyperglycemia-induced accentuation of brain injury after transient ischemia. Rats received 12.5 min of normothermic global cerebral ischemia by bilateral carotid occlusion plus hypotension. Hyperglycemia was induced before ischemia by intraperitoneal dextrose administration. Quantitative MPO immunohistochemistry was performed at 24 h and 3 days postischemia. Brains of normoglycemic-ischemic animals contained almost no MPO activity. By contrast, striking numbers of MPO-positive cells were present in brains studied 24 h after hyperglycemic ischemia, both within pial and parenchymal vessels and within the parenchyma. MPO deposition tended to subside at 3 days. These results indicate that hyperglycemia triggers the early, massive deposition of neutrophils in the postischemic brain--an event that may contribute to exacerbation of injury.
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PMID:Hyperglycemia triggers massive neutrophil deposition in brain following transient ischemia in rats. 1064 86

Ischemia/reperfusion (I/R) injury appears to be a significant neutrophil-dependent component and may be ameliorated by blocking leukocyte-endothelial adhesion. Using a rat extensor digitorum longus (EDL) muscle model, the present study tested the hypothesis that in vivo administration of the function-blocking monoclonal antibody (mAb) LAM1-116 which recognizes L-selectin, a cell-surface adhesion receptor, could decrease I/R injury. In 46 rats, one EDL served as a normal control and the opposite EDL underwent 3 hr of ischemia followed by 3 hr of reperfusion after pretreatment with LAM1-116 mAb, control IgG, or saline. Myeloperoxidase (MPO) activity showed only a two-fold increase from normal in LAM1-116-treated I/R EDL while a 27-fold increase occurred in the IgG2a and saline groups, with a statistically significant (p < 0.001) difference. A significantly (p < 0.05) lower wet weight ratio, improved fatigue contractile force, and less neutrophil infiltration were found in LAM1-116-treated EDL, when compared to those in control IgG- or saline-treated EDL. The results indicate that blockade of L-selectin by LAM1-116 mAb can effectively reduce neutrophil infiltration in reperfused skeletal muscle, thereby decreasing tissue edema and improving muscle fatigue contractile force. These findings may be important in understanding I/R injury.
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PMID:Blockade of L-selectin attenuates reperfusion injury in a rat model. 1080 28


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