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 aim of this study was to determine whether immunoneutralization of the common beta-subunit of the neutrophil CD11/CD18 glycoprotein adherence complex with monoclonal antibody IB4 (mAb IB4) or neutrophil depletion with a specific canine polyclonal antineutrophil serum (ANS) would reduce the extent of no-reflow in postischemic skeletal muscle. Microvascular patency was assessed by infusion of india ink contrast media and quantified by counting ink-containing microvessels < 15 microns diameter in histological sections obtained from isolated canine gracilis muscles subjected to 4.5 h of continuous perfusion (nonischemic control), 4 h of ischemia and 30 min of reperfusion [ischemia/reperfusion (I/R)] alone, I/R plus ANS, and I/R plus mAb IB4. I/R was associated with a marked reduction in microvascular patency compared with nonischemic controls (0.9 +/- 0.1 vs. 2.3 +/- 0.1 ink-containing microvessels per muscle fiber, respectively). Neutrophil depletion or prevention of neutrophil adherence attenuated the I/R-induced reduction in the number of ink-containing capillaries (1.6 +/- 0.1 and 2.2 +/- 0.2 ink-containing microvessels per muscle fiber, respectively). These data indicate that neutrophils play an important role in the genesis of no-reflow in postischemic skeletal muscle by a mechanism that appears to involve CD18-dependent neutrophil adhesion to the endothelium.
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PMID:CD18-dependent adherence reactions play an important role in the development of the no-reflow phenomenon. 809 75

Antibodies to the neutrophil CD18 integrin have been shown to ameliorate the local effects of intestinal ischemia and reperfusion (I/R). In addition to local mucosal injury, intestinal I/R results in systemic hypotension and injury to the lungs with lung leukosequestration. This study tests the effect of a CD18 monoclonal antibody on the hypotension and lung injury after intestinal I/R. In anesthetized rabbits, the superior mesenteric artery was clamped for 60 min followed by 3 h of reperfusion. Animals were treated with saline, an anti-CD18 monoclonal antibody (R15.7 MAb), or nonspecific immunoglobulin G. Another non-ischemic group were sham controls. Neutrophil sequestration was assessed by measure of lung myeloperoxidase (MPO) and permeability by lung-to-blood concentration ratio of 125I-labeled bovine serum albumin and wet-to-dry weight ratio. Immediately after reperfusion, mean arterial pressure fell to 49 +/- 2.1 mmHg and remained at this level. The hypotension was unaffected by treatment with R15.7 MAb. Thirty minutes after reperfusion, the circulating white blood cell count fell to 2.91 +/- 0.53 x 10(3)/mm3 vs. sham 6.40 +/- 0.66 x 10(3)/mm3 (P < 0.05). Treatment with R15.7 MAb prevented this fall in white blood cell count (5.75 +/- 1.59 x 10(3)/mm3). At 3 h of reperfusion in saline-treated animals there was increased MPO, 74.8 +/- 4.9 U/g vs. 42.0 +/- 4.8 U/g in sham animals (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A CD18 antibody prevents lung injury but not hypotension after intestinal ischemia-reperfusion. 809 7

Cardiac surgery for congenital heart disease often results in postoperative depression of myocardial function due to myocardial ischemia and stunning. The Boston Circulatory Arrest study indicated that myocardial stunning is also observed postoperatively in the immature heart. Neonates less than 3 months of age (N = 162) experienced cardiac outputs that averaged 20% of baseline values in spite of myocardium protection with Plegisol cardioplegia. In order to minimize the effects of myocardial stunning on the immature heart, we examined the effects of preischemic administration of monoclonal antibodies to leukocyte adhesion molecule CD18 (monoclonal R15.7 [Boehringer-Ingelheim]) on the function of blood perfused neonatal lamb hearts. Heart were arrested for 2 hours with a 15 degrees C K+ cardioplegia solution. Antibody treated hearts (N = 9) had significantly better (p < 0.05) recovery of left ventricular (LV) developed pressure (83.9% +/- 2.2% vs 73.6% +/- 3.0% for controls), LV dP/dt (78.4% +/- 3.3% vs 67.4% +/- 3.4% for controls), coronary blood flow (159.5% +/- 12.2% vs 84.4% +/- 3.5% for controls), and myocardial oxygen consumption (129.8% +/- 16.5% vs 71.2% +/- 6.2% for controls) than controls. In addition, recovery of coronary vascular resistance in response to 10(-6) M acetylcholine was significantly better (p = 0.08) in antibody treated hearts (38.4% +/- 4.3%) than in control hearts (13.4 +/- 12.8%). These results support the notions that leukocyte adherence to the endothelium contributes to reperfusion injury after ischemia and that monoclonal antibodies to CD18 may reduce the effects of myocardial stunning after cardiac surgery.
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PMID:Anti-CD18 attenuates myocardial stunning in the isolated neonatal lamb heart. 809 9

Ischemia is a well-known situation occurring in several diseases. There is a large body of evidence for the accumulation of neutrophils in the microvascular injury and the transformation of ischemic tissue into an inflammatory territory. However, the molecular mechanisms underlying this phenomenon are still poorly understood. The effects of hypoxia were investigated on human umbilical vein endothelial cells (HUVEC) in culture, and a very strong activation of these cells was obtained with an induction of the platelet-activating factor (PAF) synthesis which was optimal after 90 min of hypoxia. PAF was chemically identified by gas chromatography-mass spectrometry. Along with incubation under hypoxia, a constant increase in the adherence of unstimulated human polymorphonuclear neutrophils (PMN) to endothelial cells was observed. The role of PAF and of adhesion glycoproteins in this hypoxia-induced neutrophil adherence to HUVEC was then assessed. The adherence was mediated by PAF after 90 min of hypoxia as indicated by the inhibition obtained with PAF receptor antagonists and with PAF synthesis inhibition. When tested on HUVEC incubated for 120 min under hypoxia, PAF antagonists could not inhibit the PMN adherence, whereas inhibition of PAF during hypoxia could block the process, suggesting a role of PAF acting as a second messenger. In addition, the inhibitory effects obtained using monoclonal antibodies indicate that this increased adherence was also mediated by intracellular adhesion molecule 1 on HUVEC and by CD18/CD11b on neutrophils. GMP-140 seems also to be involved after 90 min hypoxia but not after 120 min hypoxia, which correlated well with the presence of PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased PMN adherence on endothelial cells after hypoxia: involvement of PAF, CD18/CD11b, and ICAM-1. 809 7

Hepatic ischemia-reperfusion injury is reported to be modulated by neutrophils (PMNs). The adhesion and emigration of PMNs that precede tissue inflammation and necrosis in other organs are mediated, in part, by the leukocyte adhesion complex CD11/CD18. In this study, the role of PMN adhesion via CD11/CD18 in isolated liver ischemia-reperfusion injury was examined in rabbits using a blocking monoclonal antibody (mAb 60.3) specific for the CD18 receptor. Vinblastine-induced neutropenia provided significant protection, confirming participation of neutrophils in the pathogenesis of hepatic injury. Inhibition of PMN adherence with mAb 60.3 did not ameliorate injury, as measured by aminotransferase concentrations or a histologic scoring system for injury severity. Histologic sections were scored for pattern and extent of injury as well as neutrophil association with injury. These results suggest a CD18-independent mechanism of neutrophil adhesion in the evolution of isolated hepatic ischemia-reperfusion injury.
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PMID:Neutrophils contribute to hepatic ischemia-reperfusion injury by a CD18-independent mechanism. 809 14

Leukocyte (WBC) adherence to endothelial cells (EC) has been implicated in the pathogenesis of microvascular injury. WBC-EC adherence is largely dependent on interaction between the WBC-CD18 complex and the endothelial ligand, intercellular adhesion molecule-1 (ICAM-1). Administration of monoclonal antibodies directed against CD18 and/or ICAM-1 inhibit WBC-EC adherence and have been reported to modulate ischemia-reperfusion and inflammatory injury. We asked the question, does inhibition of WBC-EC adherence by administration of monoclonal antibody directed against either CD18 (R15.7) or against ICAM-1 (R6.5) increase susceptibility to infection. New Zealand white rabbits were shaved and injected subcutaneously on their dorsum with Staphylococcus aureus (ATCC No. 25923) at two sites each with 10(9), 10(8), 10(7), and 10(6) colony-forming units (CFUs). A second set of rabbits were injected subcutaneously with Pseudomonas aeruginosa (ATCC No. 27853) at two sites each of 10(8) and 10(7) CFUs. Animals were monitored for 1 week with daily determination of weight, temperature, WBC counts, hematocrit, and gross evidence of abscess formation. There were three blinded experimental groups; animals given R15.7 (2.0 mg/kg), animals given R6.5 (2.0 mg/kg), and controls given saline (2.0 ml/kg). Administration of the anti-CD18 antibody, R15.7, resulted in significantly increased rates of abscess formation following innoculation with S. aureus and with P. aeruginosa, compared to controls and to the animals given the antibody to ICAM-1, R6.5. The administration of R6.5 did not increase the incidence or severity of abscess formation.
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PMID:Inhibition of leukocyte adherence and susceptibility to infection. 810 Dec 45

To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 hours after the start of reperfusion. Furthermore, pretreatment with individual monoclonal antibodies against cell adhesion molecules (CD11a, CD11bc, CD18, and intercellular adhesion molecule-1) reduced not only the infiltration of leukocytes but also the area of infarction in the reperfused hearts. These observations suggest that cell adhesion molecules play a critical role in the pathogenesis of myocardial reperfusion injury.
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PMID:Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules. 810 30

Ischemia/reperfusion involving the hind limbs of rats results in both local injury to skeletal muscle as well as injury to lungs, as measured by increased vascular permeability (125I-labeled bovine serum albumin leakage) and hemorrhage (extravasation of 51Cr-labeled rat erythrocytes). In the current study, we have focused on events in lungs occurring during reperfusion of hind limbs. Analysis of blood neutrophils obtained 4 hours after reperfusion has indicated up-regulation of CD11b and CD18 but not CD11a. Plasma from the same animals demonstrate the ability to induce similar effects in normal blood neutrophils, indicative of the presence of a neutrophil-activating agent in plasma. During reperfusion, lung injury, which develops progressively over a 4-hour period, has been shown to be neutrophil-dependent and requires CD11a/CD18 and CD11b/CD18 as well as intercellular adhesion molecule-1. These data suggest that ischemia and reperfusion injury of rat lower extremities causes systemic changes that result in neutrophil-dependent lung injury that is beta 2 integrin- (leukocyte function antigen-1, Mac-1) and intercellular adhesion molecule-1-dependent.
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PMID:Role of beta 2 integrins and ICAM-1 in lung injury following ischemia-reperfusion of rat hind limbs. 810 31

The role of complement as potential activator for tissue macrophages and neutrophils was investigated in an experimental model of endotoxin-induced liver injury in male Fischer rats. Injection of Salmonella enteritidis endotoxin (1 mg/kg) into Corynebacterium parvum-pretreated animals (7 mg/kg; single dose 6 days before endotoxin) resulted in severe oxidant stress, as indicated by a 37-fold increase of plasma levels of glutathione disulfide (basal concentration, 0.36 +/- 14 mumol/L), accumulation of neutrophils in the liver (600 +/- 31 neutrophils/50 high-power fields) and liver injury (plasma ALT, 1184 +/- 185 U/l; necrosis; 19% +/- 3%) 10 hr after endotoxin. The oxidant stress induced by 1 mg/kg endotoxin in the C. parvum-treated animals was always significantly higher than that in control animals receiving the same dose of endotoxin. Inhibition of complement activation with the soluble complement receptor type 1 attenuated the oxidant stress and liver injury by 50% to 65% but had no effect on hepatic neutrophil accumulation or plasma tumor necrosis factor-alpha levels. Treatment with a monoclonal antibody directed against the alpha-chain of CD11b/CD18 adhesion proteins (clone 17), which was highly effective in attenuating ischemia-reperfusion injury in the liver by reducing the number of neutrophils and functionally inactivating these cells, neither protected against parenchymal cell injury nor affected hepatic neutrophil infiltration in the C. parvum model. We conclude that reactive oxygen derived from complement-stimulated macrophages is critical for the development of liver injury in the C. parvum/endotoxin model.
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PMID:Contribution of complement-stimulated hepatic macrophages and neutrophils to endotoxin-induced liver injury in rats. 813 72

Matrix proteins upregulate polymorphonuclear neutrophil (PMN) oxidative metabolism in a normoxic environment. We sought to investigate the relationship between matrix proteins and adherent PMN oxidative metabolism during acute ischemia. PMN adherent to buffer, fibronectin, Arg-Gly-Asp-Ser (RGDS), or laminin were placed in either normoxic or ischemic media. PMN adherence, superoxide anion production, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan production, and surface receptor expression (CD64, CD32w, CD16, CD35, and CD11b/CD18) using monoclonal antibodies directed against these receptors were assayed. Ischemia increased PMN adherence unless the PMN were adhered to fibronectin or RGDS. Ischemia reduced PMN superoxide anion, MTT formazan, and H2O2 production unless the PMN were adhered to fibronectin or RGDS. Fibronectin and RGDS prevented ischemic-induced suppression of FcR expression. Immunofluorescent studies demonstrated capping and clustering of PMN Fc and complement receptors during ischemia while adhered on matrix proteins. These results demonstrate that 1) ischemia suppresses matrix protein upregulation of PMN oxidative metabolism, which is restored by fibronectin; 2) fibronectin-mediated restoration of PMN oxidative metabolism involves the binding epitope of fibronectin; and 3) fibronectin maintains PMN oxidative metabolism during ischemia in part by maintaining PMN FcR on the cell surface and by recruiting a new population of PMN capable of undergoing oxidative metabolism.
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PMID:Matrix protein regulation of PMN oxidative metabolism during ischemia. 816 26


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