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

Neutrophil accumulation and the consequent production of oxygen-derived free radicals are involved in the pathogenesis of Ischemia-Reperfusion syndrome. In this study we investigated whether a treatment with Vitamin E, which has antioxidant properties, could attenuate the tissue damage by interfering with the influx of neutrophils within the ischemic and reperfused human skeletal muscle. To this purpose, patients undergoing aortic cross-clamping during the surgical repair of aortic abdominal aneurysm were studied as a model of ischemia-reperfusion of the lower limb muscles. Muscle biopsies from the right femoral quadriceps of patients not receiving and receiving Vitamin E pretreatment before surgery were taken: a) after the induction of anaesthesia, as control samples, and b) after a period of ischemia followed by 30 min of reperfusion. The tissue samples were either routinely processed for morphological study and immunohistochemical analysis to detect an altered expression of specific endothelial adhesion proteins, such as E-selectin and ICAM-1. The results obtained showed that Vitamin E administration was able to prevent the accumulation of neutrophils within the ischemic and reperfused muscle. This beneficial effect of Vitamin E was due to its ability to hinder the expression of E-selectin and ICAM-1, molecules known to increase the adhesiveness of endothelium to circulating neutrophils. After treatment with Vitamin E a marked attenuation of the reperfusion injury was also evident. In conclusion, Vitamin E treatment may be considered a valuable tool for protection against the ischemia-reperfusion damage of human skeletal muscle.
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PMID:Vitamin E prevents neutrophil accumulation and attenuates tissue damage in ischemic-reperfused human skeletal muscle. 922 48

Donor livers with massive fatty infiltration reportedly are susceptible to ischemia/reperfusion injury after transplantation, which contributes to risk of primary nonfunction. We investigated the effect of warm ischemia and reperfusion on sinusoidal microcirculation in rats with fatty livers from a choline-deficient diet. Rats were subjected to partial hepatic warm ischemia for 30, 60, or 90 min. In a second study, an anti-ICAM-1 monoclonal antibody was injected intraportally 2 min after a 60-min ischemic period. In both studies, injury was assessed by liver histology 6 hr after vascular clamp release and by animal survival. After 30 min of hepatic warm ischemia, almost all control and fatty-liver rats survived 7 days. After 60-min ischemia, however, survival was significantly less in rats with fatty livers than in controls with normal livers (10% vs 90%, P < 0.0001). Histologically, rats with fatty livers showed marked sinusoidal congestion, especially in the midzone of the acinus, while control rats showed no disturbance in microcirculation. In rats with fatty livers treated with intraportal injection of an anti-ICAM-1 antibody, sinusoidal microcirculation was well preserved and the 7-day survival rate after warm ischemia was improved (50% vs no antibody 10%; P = 0.0112). In fatty livers, midzonal sinusoidal flow block occurs after hepatic warm ischemia and reperfusion. Although intraportal injection of an anti-ICAM-1 monoclonal antibody corrected this microcirculatory failure, animal survival was not as good as for controls without fatty livers. These results suggest that both sinusoidal microcirculatory failure and ischemic hepatocellular damage contribute to warm ischemia/reperfusion injury in fatty livers.
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PMID:Sinusoidal flow block after warm ischemia in rats with diet-induced fatty liver. 922 21

Experimental occlusion of a brain-supplying artery triggers tissue ischemia and subsequent inflammatory events that are initiated at the blood microvessel interface. Cytokine production and molecular adhesive events occur in the early moments following cerebral blood flow reduction, which underlie the transition from ischemic to inflammatory injury. Events both within the microvascular lumen and in the immediately surrounding tissue are involved. Cytokines, including TNF-alpha, IL-1 beta, IL-6, and PAF, are produced from the ischemic parenchyma and contribute to the endothelial cell expression of P-selectin, ICAM-1, and E-selectin. Platelet activation occurs paris passu and probably involves alpha-granule P-selectin to mediate PMN leukocyte-platelet interactions. Other integrin heterodimers are also involved in the early microvascular responses to ischemia. The response of the basal lamina and ECM is somewhat slower, entailing yet unproven mechanisms that most probably include the proteolytic processes of leukocyte transmigration. The modifications to microvascular structure are likely to affect both endothelial and astrocyte relationships, promote erythrocyte extravasation and hemorrhage, and contribute to tissue injury. Remodeling of the microvasculature, apparent in other tissues, involves a number of these processes. However, the enzymatic participants and regulating mechanisms are coming under study: the unraveling of regulatory mechanisms of adhesion receptor expression and their modulation, and the companion roles of integrins as mediators of structural integrity and intercellular signaling.
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PMID:Microvascular responses to cerebral ischemia/inflammation. 929 40

This article reviews the molecular basis of cell adhesion and its possible implications in surgery. Adhesion of circulating cells to endothelial cells is mediated by a variety of celladhesion molecules. The first steps in the cell adhesion cascade (rolling, tethering) are regulated by selectins (P, E, L selectin). Stable adhesion and transmural migration predominantly involve integrins (LFA-1, etc.) and members of the immunoglobulin supergene family (ICAM-1, etc). The mechanisms of leucocyte-endothelial interaction are markedly similar in various organs under both physiological and pathophysiological conditions. However, it is likely that cell trafficking to specific tissues/organs (e.g., homing) is regulated by additional organ-specific, topical adhesion molecules (e.g., MAdCAM-1). In surgery, cell adhesion molecules are involved in organ-transplantation pathology (ischemia/reperfusion injury, rejection), inflammation (e.g., chronic inflammatory bowel diseases), tumor metastasis. Animal experiments with anti-adhesive substances show that blocking the leukocyte-endothelial interaction reduces the cellular inflammatory infiltrate and organ rejection. The transfer of experimental data into clinical practice requires further understanding of the regulators of cell adhesion (cytokines, chemoattractant substances, etc.) and the specificity of the process. Current experimental data suggest that early intervention in cell-adhesion mechanisms may offer innovative therapeutic strategies.
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PMID:[Cell adhesion. Molecular principles and initial implications for surgery]. 930 36

This review summarized evidence in support for the case that ischemia elicits an inflammatory condition in the injured brain. The inflammatory condition consists of cells (neutrophils at the onset and later monocytes) and mediators (cytokines, chemokines, others). It is clear that de novo upregulation of proinflammatory cytokines, chemokines and endothelial-leukocyte adhesion molecules in the brain follow soon after the ischemic insult and at a time when the cellular component is evolving. The significance of the inflammatory response to brain ischemia is not fully understood. Evidence is emerging in support of the possibility that the acute inflammatory reaction to brain ischemia may be causally related to brain damage. This evidence includes: 1) the capacity of cytokines to exacerbate brain damage; 2) the capacity of specific cytokine antagonists such as IL-1ra to reduce ischemic brain damage; 3) that depletion of circulating neutrophils reduces ischemic brain injury; 4) and that antagonists of the endothelial-leukocyte adhesion interactions (e.g., anti-ICAM-1) reduce ischemic brain injury. However, it should be kept in mind that cytokines were also argued to provide beneficial effects in brain injury as inferred from studies with TNF-receptor knock-out mice (p55 and p75 knock-out), which display increased sensitivity to brain ischemia, and the capacity of IL-1 to elicit the state of ischemic tolerance upon repeated administration. Nevertheless, the recent revelation on the capacity of ischemia to induce acute inflammation in the brain provides a new and fertile ground for new explorations for novel therapeutic agents that could confine the neuronal damage that follows ischemia. Furthermore, many of the genes that are upregulated by ischemia have growth-promotion capacity and therefore raise the possibility that such gene products may be useful in counteracting brain damage by enhancing repair and establishing compensatory mechanisms that enhance histological and functional recovery.
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PMID:Inflammatory gene expression in cerebral ischemia and trauma. Potential new therapeutic targets. 936 86

Adhesion and subsequent penetration of leukocytes into central nervous system ischemic tissue proceeds via a coordinated inflammatory mechanism involving adhesion molecules at the blood-endothelium interface. Mammalian hibernation is a state of natural tolerance to severely reduced blood flow-oxygen delivery (i.e., ischemia). Hibernating thirteen-lined ground squirrels were investigated in an attempt to identify factors responsible for regulating this tolerance. Since leukocytopenia is closely associated with entrance into hibernation, the role of leukocyte adhesion to endothelium in this phenomenon was examined. Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelium and regulates interactions with circulating leukocytes that may result in margination or extravasation. ICAM-1 expression by rat cerebral microvascular endothelial cells (EC) cultured with plasma from hibernating (HP) or nonhibernating (NHP) thirteen-lined ground squirrels was dose dependently increased by HP and, to a lesser extent, by NHP. Treatment of EC with HP coincidentally induced significantly greater increases in monocyte adhesion to EC (37.2%) than were observed with NHP (23.9%). Study of the effects of HP and NHP on monocyte adhesion to EC may identify mechanisms responsible for ischemic tolerance in hibernators and could lead to the development of novel therapeutic approaches to the treatment of stroke.
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PMID:Effects of plasma from hibernating ground squirrels on monocyte-endothelial cell adhesive interactions. 943 38

A growing body of evidence indicates that neutrophils play a critical role in disrupting the microvascular barrier in skeletal muscle. Recent studies from our laboratory and by others indicate that administration of antibodies directed against P-selectin, ICAM-1, or the common subunit (CD18) of CD11/CD18 was as effective as neutrophil depletion in attenuating ischemia/reperfusion (I/R)-induced microvascular barrier disruption and edema formation in skeletal muscle. These studies have important implications with regard to the pathogenesis of leg ulceration in view of our more recent work indicating that the increase in tissue pressure induced by edema formation secondary to microvascular barrier disruption may lead to the development of capillary no-reflow. The resulting maldistribution of blood flow during reperfusion exacerbates muscle injury induced by ischemia. Daflon 500 mg is a purified, micronized flavonoid fraction that exhibits a number of anti-inflammatory properties and is used clinically to treat venous insufficiency. In view of these actions and the demonstrated role of neutrophil adhesion in the pathogenesis of I/R, we sought to determine whether this agent would prevent leukocyte adhesion and microvascular barrier disruption in postischemic rat cremaster muscles and small bowel. Rats were treated with Daflon 500 mg (80 mg/kg/day by gavage) or its vehicle for 2 (cremaster studies) or 10 (mesenteric studies) days prior to the experiments. Leukocyte/endothelial cell interactions and venular protein leakage were quantitated using intravital microscopic techniques in rat cremaster muscles and mesenteries subjected to ischemia (60 min for cremaster, 20 min for mesentery) and reperfusion (60 min). The results indicated that Daflon 500 mg was as effective as the anti-adhesive monoclonal antibodies in reducing postischemic leukocyte adhesion and emigration and venular protein leakage in these models.
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PMID:Postischemic leukocyte/endothelial cell interactions and microvascular barrier dysfunction in skeletal muscle: cellular mechanisms and effect of Daflon 500 mg. 947 39

Intercellular adhesion molecule-1 (ICAM-1) is important in neutrophil-dependent injury. We investigated the effects of monocyte chemoattractant protein-1 (MCP-1) produced by Kupffer cells on ICAM-1 expression after ischemia-reperfusion in rat liver by occluding the portal vein for 30 minutes. Serum concentrations of MCP-1 increased persistently. By Northern analysis, MCP-1 mRNA increased early and persisted. Kupffer cells harvested 6 hours after reperfusion also expressed this transcript. The transcript and protein also were produced by Kupffer cells from naive controls in response to reactive oxygen species. ICAM-1 mRNA transcripts increased, peaked 3 hours after reperfusion, and decreased gradually thereafter. The level of ICAM-1 mRNA transcripts in the WK-5 rat endothelial cell line were markedly enhanced by MCP-1. These results suggest that MCP-1 released by Kupffer cells early after ischemia-reperfusion modulates neutrophil-dependent tissue injury via ICAM-1.
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PMID:Monocyte chemoattractant protein-1 enhances expression of intercellular adhesion molecule-1 following ischemia-reperfusion of the liver in rats. 950 Jul 1

Since the first documentation of the induction of heat shock protein following transient cerebral ischemia, much experimental evidence suggested that all of the cellular elements in the central nervous system show dynamic stress responses depending on the degree of environmental changes induced by ischemia and reperfusion. In this review, first I focused on the importance of the usage of an appropriate experimental model for brain ischemia and reperfusion, and I presented our work on mouse models of transient global and focal ischemia. Next, I reviewed the pathogenic role of microvascular stasis (i.e., secondary ischemia) caused by the primary ischemic event and demonstrated the important role of cell adhesion molecules through the experiments using ICAM-1 knock-out mouse as a model of brain ischemia/reperfusion. Thirdly, I discussed the ischemia-induced neuronal cell responses in relation to the apoptosis-like selective neuronal death and the induction of adopted stress responses including stress protein synthesis and 'ischemic tolerance' phenomenon. A variety of stress proteins induced by ischemic stress have been reviewed and a pivotal role of tyrosine kinase system in selective neuronal death has been suggested in the gerbil model of transient forebrain ischemia. Finally, I showed the important pathophysiological roles of glial cells such as astrocytes and oligodendrocytes in the cellular cross-talk triggered by an ischemic event. For the development of a novel therapeutic agent against ischemic stroke, it is quite important to clarify both the negative and positive cellular responses induced by brain ischemia/reperfusion.
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PMID:[Dynamic cellular response following brain ischemia and reperfusion]. 955 67

A total of 12 mongrel dogs were divided into two equal groups. Six animals received IIoprost and the other 6 animals did not receive any additional treatment. In the Iloprost group, Iloprost was added to the cardioplegic solution (25 ng). Also, Iloprost was used (10 ng/kg/min.) 5 min. before and after cross-clamping. All cardiac output and biochemical measurements were evaluated before cross-clamp and 15 min., 1 h, and 4 h after cross-clamp. The measured dp/dt shows that the hearts treated with Iloprost preserved left ventricular function. Comparison of contractility indices between the groups revealed that contractile recovery was 59% in the control group and 71% in the Iloprost group (p < 0.05). Tumor necrosis factor (TNF) alpha level was significantly elevated in the control group (p < 0.001). Its level was 22.2 +/- 2.2 pg/mL in the control group and 13.8 +/- 1.0 pg/mL in the Iloprost group. E- and P-selectin levels were elevated in the control group (p < 0.001). ICAM-1 level was also elevated in the control group. ICAM-1 level was 17.7 +/- 1.8 ng/mL in the control group and 8.5 +/- 1.8 ng/mL in the Iloprost group. The Iloprost that was added to the cardioplegic solution and low dose administration during the pre- and post-ischemic period inhibits the toxic mediator release from endothelium-leukocyte interaction and reduces the severity of ischemia-reperfusion injury.
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PMID:Iloprost added to the cardioplegic solutions improves myocardial performance. 966 Dec 18


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