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

Intestinal ischemia-reperfusion injury is a common and important clinical event associated with the activation of an endogenous inflammatory response. Some of the mediators of this response may be involved in the pathogenesis of multiple organ system failure. The purpose of this study was to determine whether remote organ dysfunction--specifically, acute lung injury--occurs after intestinal ischemia-reperfusion injury. After an ischemia-reperfusion event in rat intestine, whole lungs were obtained for measurement of tissue adenosine triphosphate (ATP) and myeloperoxidase values, and evaluation of histologic condition. In addition, lung microvascular permeability was assessed by determination of the rate at which iodine 125-labeled bovine serum albumin sequestration in the extravascular compartment occurred. Lung tissue ATP levels were no different in sham-operated animals than in those that had undergone 120 minutes of intestinal ischemia. Within 15 minutes of gut reperfusion, however, lung ATP decreased from 3.82 +/- 0.27 to 1.53 +/- 0.90 x 10(-7) moles/50 mg tissue, p less than 0.05. Neutrophil accumulation in the lungs, estimated by tissue myeloperoxidase determination, increased sevenfold (0.13 +/- 0.02 to 0.97 +/- 0.25 units/gm, p less than 0.05) after 120 minutes of ischemia and 15 minutes of reperfusion. Lung microvascular permeability increased threefold after 120 minutes of intestinal ischemia and 120 minutes of reperfusion (0.10 +/- 0.01 vs. 0.35 +/- 0.05 [lung/blood counts per minute], p less than 0.05). Intestinal ischemia followed by reperfusion is associated with acute lung injury characterized by increased microvascular permeability, histologic evidence of alveolar capillary endothelial cell injury, reduced lung tissue ATP levels, and the pulmonary sequestration of neutrophils. These data confirm an acute lung injury associated with intestinal ischemia-reperfusion and suggest a possible pathogenic role for the neutrophil.
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PMID:Evidence for neutrophil-related acute lung injury after intestinal ischemia-reperfusion. 276 27

The influence of quinacrine on malondialdehyde (MDA) as an index of lipid peroxidation, activities of phospholipase A2 (PLA2), and myeloperoxidase (MPO)--a neutrophil granulocyte maker in plasma--was examined in rats following ischemia and reperfusion. In the absence of quinacrine, ischemia and reperfusion caused increased MDA content and increased activities of PLA2 and myeloperoxidase in the plasma. All these effects were efficiently inhibited by the PLA2 inhibitor quinacrine. The finding indicates that the occurrence of an increased level of MDA following intestinal ischemia may be used for diagnostic purposes and points to the possibility that high plasma MDA might indicate a need for PLA2 inhibitor treatment.
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PMID:Influence of quinacrine on plasma malondialdehyde after small intestinal ischemia and reperfusion. 283 Sep 96

This study investigates the action of intravenous PGE1 on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE1 (5 micrograms/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE1 treatment. PGE1 exerted some blood-pressure-lowering activity at 5 h (P greater than 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE1 modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE1 prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE1 protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.
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PMID:Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation. 284 5

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals may mediate the microvascular and parenchymal injury produced by reperfusion of ischemic skeletal muscle. One potential source of these reactive oxygen metabolites is the inflammatory neutrophil. To assess neutrophil accumulation in postischemic skeletal muscle, we measured tissue myeloperoxidase (MPO) activity in skeletal muscle biopsies taken during control, after 4 h of ischemia, and after 1 h of reperfusion. Tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured in the same samples to identify alterations in tissue free radical defense mechanisms due to ischemia-reperfusion. Reperfusion of ischemic skeletal muscle was associated with a dramatic increase in tissue neutrophil content (as reflected by a 26-fold increase over control in tissue MPO activity after 1 h of reperfusion) and a concurrent 50% decrease in GSH content. Tissue CAT and SOD activities were unaffected by ischemia-reperfusion. These results suggest a possible relationship between ischemia-reperfusion-induced injury, neutrophil infiltration, and the reduction in tissue GSH.
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PMID:Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle. 292 39

Platelets are suggested to exacerbate ischemia-induced myocardial injury, which has led to the study of various antiplatelet therapies including thromboxane synthetase inhibitors (TXSI). Two such agents, benzylimidazole and OKY-046, reduce infarct size commensurate with a diminution in serum thromboxane B2 formation in anesthetized dogs subjected to 90 minutes of coronary artery occlusion followed by 5 hours of reperfusion. In contrast, platelet depletion with specific antiserum does not reduce infarct size but prevents the cardioprotection afforded by the TXSI. Platelet-derived prostaglandin endoperoxides (PGG2 and PGH2), which cannot be converted to thromboxane A2 in the inhibited platelet, can be transformed to PGE2 and PGD2 in plasma and to PGI2 by the blood vessel wall. These prostaglandins are considered "cardioprotective." Consequently, a low dose of aspirin (3-5 mg/kg) given 24 hours before coronary occlusion was used to selectively block the platelet cyclooxygenase enzyme. Aspirin, by itself, does not reduce infarct size, but it suppresses the myocardial salvage induced by OKY-046. Thus, TXSI reduce infarct size by platelet-dependent, aspirin-sensitive mechanism that depends on the redirection of platelet-derived PGG2 and PGH2 to protective metabolites, rather than inhibition of thromboxane A2 per se. Moreover, myocardial salvage induced by the TXSI is accompanied by a reduction in neutrophil accumulation in the myocardium, as indicated by the levels of the neutrophil-specific myeloperoxidase enzyme. Platelet depletion or pretreatment with aspirin prevents the TXSI-induced suppression of neutrophil accumulation. Consequently, it is proposed that the prostaglandin-mediated protective effects of TXSI can be resolved, at least in part, in terms of a braking action on neutrophil activation to prevent leukocyte-dependent tissue injury.
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PMID:Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. 312 73

The purpose of this study was to determine whether fructose-1,6-diphosphate (FDP) or adenosine (Ado), administered at the onset of reperfusion, would prevent ischemia/reperfusion (I-R)-induced leukocyte adherence and microvascular dysfunction in skeletal muscle. Changes in vascular permeability and tissue neutrophil content were assessed by measurement of the solvent drag reflection coefficient (delta) for total plasma proteins and muscle myeloperoxidase (MPO) activity, respectively, in continuously perfused, isolated canine gracilis muscles and in muscles subjected to I-R alone, I-R + FDP, and I-R + Ado. To determine whether FDP or Ado would attenuate leukocyte-endothelial cell adhesive interactions induced by I-R, leukocyte adherence and emigration were assessed in postischemic mouse cremaster muscles, using intravital microscopy in the presence and absence of FDP or Ado during reperfusion. I-R was associated with a marked increase in microvascular permeability and muscle MPO activity relative to nonischemic controls. These increases were attenuated by FDP and Ado. I-R also increased the number of adherent and emigrated leukocytes relative to control. I-R-induced leukocyte adherence and emigration were significantly attenuated by either FDP or Ado. These results indicate that FDP and Ado attenuate postischemic microvascular barrier dysfunction in skeletal muscle by a mechanism that may be related to their ability to inhibit leukocyte adhesion and emigration.
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PMID:Fructose-1,6-diphosphate or adenosine attenuate leukocyte adherence in postischemic skeletal muscle. 750 73

Hemorrhagic mucosal lesions are produced during intestinal ischemia and after reperfusion due at least in part to the accumulation and activation of polymorphonuclear leukocytes in the tissue. It has been shown in vitro that adenosine is instrumental in attenuating this pathophysiological process. Acadesine [5-amino-4-imidazolecarboxamide (AICA) riboside], a purine nucleoside analogue, increases the availability of adenosine in the tissue. The aim of the study was therefore to assess the influence of acadesine treatment on neutrophil accumulation, purine metabolism, and mucosal damage after intestinal ischemia and reperfusion. Intestinal ischemia was induced in cats by partial occlusion of the superior mesenteric artery for 2 h. Samples of the small intestine were exercised before and at the end of the hypotensive period as well as 10 and 60 min after reperfusion. Conjugated dienes, myeloperoxidase, and reduced and oxidized glutathione, as well as the purine metabolites, were determined in the tissue samples. The tissue was also examined histologically. Six cats received saline, and six cats were treated initially before ischemia with acadesine (2.5 mg/kg body wt i.v.) over 5 min as a bolus. Thereafter, acadesine (0.5 mg.kg-1.min- i.v.) was given continuously during ischemia and 30 min after reperfusion. Acadesine treatment significantly attenuated the mucosal lesions seen during reperfusion. This improvement was due at least in part to the inhibition of neutrophil accumulation, as judged by low myeloperoxidase levels. The prevention of neutrophil activation resulted most likely from increased adenosine concentrations in the intestinal tissue in the early reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of acadesine treatment on postischemic damage to small intestine. 750 74

The cardioprotective actions of SPM-5185, a novel cysteine-containing nitric oxide (NO) donor, were investigated in two models of myocardial ischemia-reperfusion (MI-R) injury. In the first study, dogs were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion followed by 270 min of reperfusion. During reperfusion, animals were randomly assigned to receive intracoronary SPM-5185 (500 nM) or the NO-deficient analogue of SPM-5185, SPM-5267 (500 nM). Transmural myocardial blood flow to the ischemic zone was not different between the SPM-5185 group of dogs and the SPM-5267 group (0.04 +/- 0.01 and 0.03 +/- 0.01 ml/min/g, respectively). Similarly, the area of left ventricular myocardium placed at risk by LAD coronary artery occlusion was equivalent in dogs receiving SPM-5185 (33.6 +/- 3%) and SPM-5267 (30.4 +/- 2%). However, the necrotic area, expressed as a percentage of the area at risk, was reduced by 70% in the SPM-5185-treated dogs (14.5 +/- 4 vs. 47.5 +/- 9%; p < 0.001). Furthermore, cardiac myeloperoxidase activity indicated that fewer neutrophils accumulated in the necrotic zone of the SPM-5185-treated dogs. In the second study, dogs were subjected to 30 min of global myocardial ischemia followed by 1 h of cardioplegic arrest and 1 h of reperfusion. SPM-5185 (10 microM) added to the blood cardioplegia solution resulted in a 95 +/- 14% post-ischemic recovery of contractile function compared with 36 +/- 8% (p < 0.05) in vehicle-treated dogs. Additionally, SPM-5185 treatment completely preserved coronary arterial vasorelaxation to acetylcholine after ischemia and reperfusion and resulted in a 62% reduction in cardiac tissue myeloperoxidase activity (p < 0.05). We conclude that (a) SPM-5185 exerts significant cardioprotection from MI-R injury after regional or global ischemia, and (b) this cardioprotection appears to be related to the inhibition of neutrophil-mediated injury.
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PMID:Endothelial and myocardial cell protection by a cysteine-containing nitric oxide donor after myocardial ischemia and reperfusion. 750 67

We wished to determine if the previously observed cardioprotective effects of monophosphoryl lipid A (MLA, 65 micrograms/kg intravenously, i.v.), an endotoxin derivative, were time related and mediated by an enhancement of antioxidant defense mechanisms, i.e., myocardial catalase and superoxide dismutase (SOD) activities and neutrophil infiltration as assessed by myeloperoxidase (MPO) activity. We also wished to study the effect of pretreatment with MLA on vascular endothelial and smooth muscle function in vivo and in vitro. Barbital-anesthetized dogs were subjected to 60-min left circumflex coronary artery (LCX) occlusion followed by 5-h reperfusion. Myocardial catalase, SOD, and MPO activities were measured at the end of 5-h reperfusion. Pretreatment with MLA 24 h before ischemia produced a significant reduction in myocardial infarct size as measured by triphenyltetrazolium staining (15.3 +/- 4.4 vs. 30.9 +/- 5.2% in controls, p < 0.05), but 1-h pretreatment with MLA had no protective effect. MLA pretreatment for 24 h resulted in marked reduction (p < 0.05) in MPO activity in the border zone surrounding the infarct. Although a trend indicated an increase in catalase activity in the 24-h pretreatment group, no significant changes were observed in either catalase or SOD activities among the three groups. The cardioprotection produced by MLA was independent of differences in collateral blood flow to the ischemic region assessed by radioactive microsphere technique, systemic hemodynamics, myocardial oxygen demand, and ischemic bed size. Responses of the LCX bed to intracoronary acetylcholine (ACh) or nitroglycerin (NTG) in vivo and responses of isolated femoral artery rings to the endothelium-dependent vasodilators, ACh, A23187, bradykinin, or the nonendothelium-dependent vasodilator, sodium nitroprusside (SNP) in vitro were significantly decreased in the MLA 1-h pretreatment group but not in the 24-h pretreatment group. Incubation of the femoral artery rings from the MLA 1-h pretreatment group with 3 mM L-arginine for 1 h reversed the decreased endothelium-dependent responses to ACh and A23187, but not those to bradykinin. These results indicate that (a) the MLA-induced myocardial infarct size reduction was pronounced when MLA was administered for 24 h but was not evident at 1-h pretreatment; (b) a decrease in neutrophil infiltration into the site of ongoing tissue damage might be partially responsible for the protection; (c) vascular endothelial and/or smooth muscle function were transiently decreased by MLA administration and returned to nearly normal levels 24 h after treatment; and (d) the effect of MLA on endothelium-dependent responses might be mediated by the L-arginine/nitric oxide (NO) pathway.
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PMID:Effects of monophosphoryl lipid A on myocardial ischemia/reperfusion injury in dogs. 750 70

The objective of this study was to determine whether pulmonary endothelial expression of the adhesive glycoprotein P-selectin contributes to the lung injury and leukostasis observed after intestinal ischemia-reperfusion (I/R). The pulmonary capillary filtration coefficient and lung myeloperoxidase activity were determined in rat lungs isolated after 120 min of superior mesenteric artery occlusion and 90 min of reperfusion. Intestinal I/R resulted in a marked increase in the pulmonary capillary filtration coefficient compared with control and sham-operated rats. The increase in pulmonary microvascular permeability elicited by intestinal I/R was effectively prevented by pretreatment with a P-selectin monoclonal antibody (MAb; MAb PB1.3) but was unaffected by a control MAb. The intestinal I/R-induced increase in pulmonary microvascular permeability was accompanied by a dramatic sequestration of granulocytes in the lung compared with control and sham-operated rats; however, neither the P-selectin nor the control MAbs affected this event. These results indicate that P-selectin contributes to the pulmonary microvascular dysfunction observed after intestinal I/R. The inhibition of intestinal I/R-induced lung injury by immunoneutralization of P-selectin appears to be unrelated to the accompanying lung leukosequestration.
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PMID:Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P-selectin. 751 Feb 79


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