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

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.
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PMID:Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. 189 66

Various beneficial effects of calcium channel blockers on cell and organ function following endotoxic shock, organ ischemia, and reperfusion have been reported; however, it is not known whether these agents have any salutary or deleterious effects on immune responses after low-flow conditions. Therefore, the aim of this study was to determine (a) the effect of hemorrhage on lymphocyte IL-2, IL-3, IL-6, and IFN-gamma synthesis, and (b) whether diltiazem has any salutary or adverse effects on these parameters when administered following hemorrhage and resuscitation. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg, maintained at that level for 60 min, and resuscitated with shed blood plus twice that volume of Ringer's lactate. Immediately following resuscitation mice received either diltiazem (2400, 800, or 400 micrograms/kg body wt), or an equivalent volume of saline. The mice were sacrificed 24 hr later, splenic lymphocytes were obtained, and their capacity to produce lymphokines was assessed. The results indicated that in the vehicle-treated animals, hemorrhage significantly decreased (P less than 0.05) IL-2, IL-3, IL-6, and IFN-gamma synthesis by 82 +/- 19%, 64 +/- 28%, 71 +/- 11%, and 86 +/- 14%, respectively. However, diltiazem (400 but not 2400 micrograms/kg) treatment after hemorrhage restored lymphocyte capacity to produce IL-2, IL-3, IL-6, and IFN-gamma (P less than 0.05). Additional groups of animals were subjected to sepsis by cecal ligation and puncture 3 days following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diltiazem restores IL-2, IL-3, IL-6, and IFN-gamma synthesis and decreases host susceptibility to sepsis following hemorrhage. 190 99

Cytokines are important mediators of the inflammatory reaction and microvascular injury after trauma and tissue ischemia. The plasma activity of a cytokine reflects the net effect of positive and negative signals. We examined the sequential serum activity of IL-1, IL-2, IL-6, and TNF in a severe model of splanchnic artery occlusion (SAO) shock induced in rats by total occlusion of the superior mesenteric and the celiac arteries for 40 min. A control group with negligible surgical intervention and two sham-shock groups, one with minor operation and another with major surgery employed in SAO rats, both without vascular occlusion, were also studied. No IL-1 activity was detected throughout the 190-min experimental protocol in any of the groups. Low activity of IL-2 was measured only in SAO rats (approximately 1 U/ml at the peak). We found graded increases in serum TNF and IL-6 activities which were proportional to the surgical trauma and were highest in SAO rats (IL-6 up to 30 U/ml, P less than 0.01 from both sham groups; TNF, 2500 pg/ml 30 min after reperfusion, P less than 0.01 from both sham groups). These data further support the role played by cytokines in the early mediation of surgical trauma and shock.
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PMID:Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats. 191 66

While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion. These results provide evidence for local expression of cytokine mRNA in postischemic myocardium and suggest that regulation of local cytokine release is altered during the postischemic period.
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PMID:Cytokine mRNA expression in postischemic/reperfused myocardium. 785 52

A period of cold and warm ischemia is obligatory when performing lung transplantation. Subtle ischemia-reperfusion injury induced in the course of transplantation can pass undetected or cause a short phase of reversible lung dysfunction. We hypothesized that ischemia-reperfusion injury may result in the local release of cytokines that have the capability to mediate acute lung injury early following transplantation. To test this hypothesis, 10 mongrel dogs were subjected to left lung allotransplantation. As performed in the clinical setting, donor lungs were preserved with Eurocollins solution and stored at 4 degrees C for 4 hr, which was followed by 1 hr of warm ischemia. Recipients received standard immunosuppression of cyclosporine, azathioprine, and low dose steroids. Bronchoalveolar lavage (BAL) and open lung biopsies were performed before operation and at approximately 1 hr, 4 hr, 24 hr, and 1 week after transplantation. A significant increase in BAL IL-2 levels was observed 4 hr after surgery (0 hr: 349 +/- 138 pg/ml; 4 hr: 757 +/- 284 pg/ml) (mean +/- SEM) (P < 0.05) which subsequently decreased 24 hr (320 +/- 168 pg/ml) after transplantation. BAL TNF-alpha levels were significantly increased 1 hr after transplantation (P < 0.05) (0 hr: 3.4 +/- 0.65 pg/ml; 1 hr: 13.3 +/- 8.0 pg/ml) returning to baseline after 24 hr (5.8 +/- 2.8 pg/ml). BAL IFN-gamma levels also significantly increased 1 and 4 hr after transplantation (0 hr: 7.2 +/- 2.1 pg/ml; 1 hr: 68.2 +/- 49.2 pg/ml; 4 hr: 301 +/- 131 pg/ml) (P < 0.05). This decreased back to baseline after 24 hr and 1 week (5.2 +/- 1.2 pg/ml and 9.7 +/- 7.9 pg/ml, respectively). There were no changes detected in plasma levels of cytokines. Histology showed evidence of grade 1-2 rejection after 1 week. We conclude that subjection of a lung allograft to standard periods of cold-warm ischemia will result in a temporary early elevation of IL-2, TNF-alpha, and IFN-gamma detectable only in the bronchoalveolar compartment. Such local increase in cytokines in the lung allograft may play an important role in the development of early allograft dysfunction.
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PMID:The early release of interleukin-2, tumor necrosis factor-alpha and interferon-gamma after ischemia reperfusion injury in the lung allograft. 799 55

Ischemia is an interruption of oxygen and nutrient supply to a determined area of tissue for a period of time. Because of the heterogeneity of various tissues with regard to their microvascular flow reserve and oxidative capacity, as well as their markedly different metabolic needs, a single critical Po2 level below which ischemia occurs is unlikely. This is why there are variations of tolerance to hypoxia within and among organs. In general, when Pao2 reaches approximately 5 torr there is already evidence, in some organs, of altered cellular energetics. In addition, cessation of flow impairs the incoming transfer of nutrients such as glucose, and cells must depend on their own intracellular stores of carbon radicals, if available. Epidemiologic data suggest that there are deleterious effects of hypoxia on the immune system and that these effects result in increased susceptibility to infection. The histology of ischemic tissues demonstrates intravascular neutrophil (PMN) accumulation, vascular damage, and increased vascular permeability. Expression of PMN adhesion receptors is increased when oxygen is nearly completely removed from the medium. Expression of integrins on the cell surface is regulated by intracellular calcium; hypoxia causes a sustained and prolonged increase of intracellular calcium levels. Because both granule movement and functional expression of adhesion receptors on the cell surface are important in leukocyte motility, chemotaxis, and phagocytosis, these functions may be impaired by hypoxia. Exposure of a human macrophage cell line to nonlethal levels of hypoxia causes in vitro release of significant amounts of biologically active cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1 and IL-8, as well as expression of intercellular adhesion molecule-1 and bound and soluble receptors for TNF alpha. Hypoxia markedly decreases T-lymphocyte IL-2 messenger RNA, a key cytokine responsible for B-cell proliferation and immunoglobulin secretion.
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PMID:Leukocyte responses to hypoxic/ischemic conditions. 877 94

Cytokines have been implicated as pivotal mediators of the wound-healing process. An understanding of the production and interaction of cytokines may lead to a better appreciation of the complex mechanisms of flap ischemia. The potential would then exist for novel diagnostic and therapeutic approaches to prevent and reverse damage to the endangered flap. The goal of this study was to determine the expression of parenchymal cytokines at various time points during flap ischemia. Punch biopsies were obtained from McFarlane dorsal flaps in the Sprague-Dawley murine model. We examined cytokine mRNA profiles for interleukin 1 alpha (IL-1 alpha), IL-2, IL-6, basic fibroblast growth factor (b-FGF), gamma-interferon (gamma IFN), transforming growth factor beta (TGF-beta), and platelet-derived growth factor A chain (PDGF-alpha) using in situ hybridization. Samples were taken from 0 to 48 hours postoperatively, with n = 3 for each time point. Eight hours postoperatively there was an abrupt peak of parenchymal cytokine expression at the bases of the flaps. Clinically at this time the flaps appeared completely viable without evidence of ischemic change. Leukocyte cytokine production peaked at 16 hours, when distal flap ischemia was evident clinically. These findings demonstrate an early peak of cytokine expression prior to clinical evidence of ischemia.
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PMID:Parenchymal cytokine expression precedes clinically observed ischemia in dorsal flaps in the rat. 882 26

Events in the early post-transplant period have been correlated with increased renal allograft loss. Immunologic reactions and ischemic injury have been implicated in this process. While the immunologic aspects of allograft injury have been studied extensively, ischemic effects remain less well understood. To study the effects of ischemia in rats with different genetic backgrounds without the introduction of an alloimmune response, a clamp was placed on the vascular pedicle of the left kidney for 60 min. The short-term effects (1 wk) of ischemia were studied in groups of PVG (RT1c), LEW (RT1), DA (RT1a) and WR (RT1u) rats, Immunoperoxidase staining demonstrated limited infiltration of monocytes, macrophages, and T-cells accompanied by upregulation of low levels of MHC class II antigens on tubular epithelial cells, peritubular capillaries, and interstitial cells in kidneys of PVG and WF rats. Kidneys of LEW and DA rats had greater influxes of monocytes, macrophages, and T cells in addition to higher amounts of MHC class II antigens upregulation on tubular epithelium and interstitial cells. The long-term effects of ischemia were studied in kidneys of WF rats. These kidneys had a progressive increase in infiltrating T cells, monocytes, macrophages and MHC class II expression on the tubular epithelium and the interstitial cells at 14, 30, and 90 d after the ischemic insult. The differences in MHC class II expression between ischemic kidneys of PVG and LEW rats were not associated with differences in production of mRNA for IL-2, IFN-gamma, and TNF-alpha. In summary, transient renal ischemia in the absence of an allogeneic immune response triggers a progression of inflammatory responses, including leukocyte infiltration, cytokine production and MHC class II antigen upregulation which appears to be strain-dependent.
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PMID:Immunohistochemical manifestations of unilateral kidney ischemia. 899 59

Ischemia/reperfusion (I/R) injury associated with renal transplantation may influence both early graft function and late changes. The initial (</= 7 d) events of warm and in situ perfused cold ischemia of native kidneys in uninephrectomized rats were examined. mRNA expression of the early adhesion molecule, E-selectin, peaked within 6 h; PMNs infiltrated in parallel. T cells and macrophages entered the injured kidney by 2-5 d; the associated upregulation of MHC class II antigen expression suggested increased immunogenicity of the organ. Th1 products (IL-2, TNFalpha, IFNgamma) and macrophage-associated products (IL-1, IL-6, TGFbeta) remained highly expressed after 2 d. To examine directly the effects of selectins in I/R injury, a soluble P-selectin glycoprotein ligand (sPSGL) was used. Ischemic kidneys were perfused in situ with 5 microg of sPSGL in UW solution; 50 microg was administered intravenously 3 h after reperfusion. E-selectin mRNA remained at baseline, leukocytes did not infiltrate the injured organs throughout the 7-d period, and their associated products were markedly inhibited. Class II expression did not increase. No renal dysfunction secondary to I/R occurred. The early changes of I/R injury may be prevented by treatment with soluble P- and E-selectin ligand. This may reduce subsequent host inflammatory responses after transplantation.
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PMID:The cytokine-adhesion molecule cascade in ischemia/reperfusion injury of the rat kidney. Inhibition by a soluble P-selectin ligand. 916 98

The role of nitric oxide in the airway hyperresponsiveness and inflammation of bronchial asthma has not yet been established. However, L-arginine, the substrate for nitric oxide synthases, reportedly alleviates airway hyperresponsiveness caused by parainfluenza virus and reduces granulocytic inflammation induced by ischemia-reperfusion. We investigated the effects of L-arginine on a murine model of allergic asthma that included airway hyperresponsiveness, eosinophilic inflammation and expression of interleukin (IL)-5 in the lung. The mice received drinking water with or without L-arginine for 9 weeks. Histologic evaluation and cellular profiles in bronchoalveolar lavage fluid showed that p.o. administration of L-arginine (72 micromol/kg/day) significantly enhanced eosinophilic airway inflammation and goblet cell proliferation that were associated with intratracheal instillation of ovalbumin. L-Arginine also increased protein levels of IL-5 and IL-2 in supernatants from the lung exposed to ovalbumin. The number of eosinophils in bronchoalveolar lavage fluid correlated significantly with the expression of IL-5. L-Arginine did not reverse ovalbumin-associated airway hyperresponsiveness to inhaled ACh. These results suggest that p.o. administration of L-arginine aggravates allergen-induced eosinophilic airway inflammation via expression of IL-5, and in this model it does not show therapeutic efficacy against airway hyperresponsiveness associated with allergen exposure. Oral administration of L-arginine, the precursor of nitric oxide, may not be an effective intervention in allergic asthma.
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PMID:Oral administration of L-arginine potentiates allergen-induced airway inflammation and expression of interleukin-5 in mice. 969 32


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