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)

In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.
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PMID:The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver. 128 66

Iloprost has been shown to minimize skeletal muscle necrosis when administered before the onset of ischemia in animal experiments, possibly by preventing neutrophil activation. Since patients with acute limb ischemia are seen after the process has begun, we investigated whether iloprost can be protective when given only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a standard isolated gracilis muscle preparation. In six control animals (group I) the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle ischemia and throughout the experiment (6 hours of ischemia and 1 hour of reperfusion). In addition to the continuous infusion, they received 0.45 microgram/kg intravenous boluses of iloprost 10 minutes before the induction of ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a similar ischemic interval, but were given a bolus of iloprost of 0.45 microgram/kg at end ischemia followed by continuous infusion of 0.45 microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at baseline and after 1 hour of reperfusion in all groups. Additional biopsies were obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase activity, a marker of neutrophil activation, was measured in all muscle biopsies. At the end of reperfusion, the gracilis muscle was harvested in all animals and weighed. Muscle necrosis was estimated by serial transection, nitroblue tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The value and limitation of iloprost infusion in decreasing skeletal muscle necrosis. 137 47

Iloprost (a long-acting prostacyclin analog) has been demonstrated to decrease cardiac muscle infarct size after ischemia-reperfusion injury. We investigated the ability of iloprost to decrease skeletal muscle injury and platelet sequestration after ischemia-reperfusion injury in a canine bilateral isolated gracilis muscle model. Anesthesized animals (n = 13) were subjected to 6 hours of gracilis muscle ischemia and 1 hour of reperfusion. Fifteen minutes before muscle reperfusion, the animals were infused with radium 111-labeled autogenous platelets. Experimental animals (n = 7) received a continuous preischemic intravenous infusion of iloprost (0.45 microgram/kg/hr) and two 0.45 microgram/kg intravenous injections of iloprost (10 minutes before the ischemic interval and 10 minutes before reperfusion). Muscle injury was measured with triphenyltetrazolium chloride histochemical staining. Platelet sequestration within ischemic muscle specimens was determined by measuring indium 111 activity in a gamma counter. Iloprost infusion decreased muscle infarct size from 57.0% +/- 12.6% in control animals to 15.8% +/- 4.4% in experimental animals (p less than 0.05). Platelet uptake in experimental and control muscle was 1.2 +/- 0.21 x 10(7) and 2.17 +/- 0.48 x 10(7) platelets/gm ischemic muscle, respectively (p = 0.1). Although platelet sequestration was not altered significantly in this experiment, a reduction in skeletal muscle injury was confirmed. Further investigation on the mechanisms of action of iloprost in chronic and acute skeletal muscle ischemia is warranted.
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PMID:Iloprost infusion decreases skeletal muscle ischemia-reperfusion injury. 168 31

Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified.
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PMID:Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion. 170 Aug 37

Operative trauma, ischemia, release of catecholamines and thermal stimuli in consequence of harvesting, preservation and transplantation deteriorate the renal capillary circulation. By crossing of tolerance limits arises an irreversible transplant damage. The conditions of our examinations were placed in this field. By pre- and postischemic application of Iloprost was demonstrable an improvement of the ischemic tolerance of the kidney. Correction of renal hemodynamics, antiplatelet action and cytoprotection are the reasons of the protective influence of Iloprost in our opinion.
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PMID:[The improvement of the tolerance of the kidney for ischemia with the prostacyclin analog iloprost]. 170 19

This study of the postischemic events in the hamster cheek pouch showed that there is an increase in number of leukocytes adhering to the venular endothelium after reperfusion. It also showed that the stable prostacyclin analogue Iloprost could counteract both the postischemic increase in leukocyte adhesion and the postischemic increase in vascular permeability to macromolecules. The hamsters were anesthetized and the cheek pouch was everted and prepared for intravital microscopy. Temporary ischemia (30 min) was obtained using an expandable cuff placed around the proximal part of the cheek pouch. Fluorescein labelled dextran (FITC-dextran, Mw 150,000) was used as a tracer of macromolecular leakage from the postcapillary venules. Iloprost, given either topically (0.1 nM) or as an intravenous infusion (40 ng/kg/min), reduced the postischemic permeability increase (P less than 0.05) but did not affect the hemodynamics or the permeability response induced by histamine. It is proposed that these effects could be due to inhibition of leukocyte activation by Iloprost, indicating that these cells could play a role in the permeability increase during reperfusion after ischemia.
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PMID:Modification of postischemic increase of leukocyte adhesion and vascular permeability in the hamster by Iloprost. 170 55

Protective effects of prostacyclin (PGI2) and Iloprost in experimental cardiac ischemia are reported by several authors. However, the effects of continuous administration on the final outcome of myocardial infarction are not yet known. We investigated the effects of Iloprost on cardiac unperfused area (UA) and necrotic zone (NZ) as assessed by Evans blue perfusion and extraction and nitrobluetetrazolium staining, respectively, using osmotic minipumps for continuous intravenous drug administration. Starting 3-4 hours after left descending coronary artery-ligation (LAD-L) Iloprost was infused at doses of 0.1 microgram and 0.5 microgram X kg-1 X min-1. While the lower dose is below pharmacological effect level, the higher dose in rats slightly lowered blood pressure and effectively inhibited platelet aggregation. LAD-L in control rats resulted in UA and NZ extending to 34.2 and 16.9%, respectively, of total ventricular mass (VM) after 24 hours and 28.3 and 21.3% of VM, respectively, after 7 days. At the dose of 0.1 micrograms X kg-1 X min-1 Iloprost was ineffective in reducing UA 24 hours after LAD-L. However, at 0.5 microgram X kg-1 X min-1 Iloprost with UA and NZ of 16.3 and 8.4% of VM, respectively, after 24 hours and 8.5 and 5.2% of VM, respectively, after 7 days reduced the extension of myocardial infarction by approximately 50% after 24 hours and 70% after 7 days, as compared to controls. As assessed in unperfused ventricular tissue after LAD-L and normal myocardium of sham-operated rats following 24 hours of Iloprost infusion, myocardial tissue concentrations of Iloprost amount to approximately half of the plasma levels irrespective of LAD-L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Limitation of myocardial unperfused area and necrotic zone 24 hours and 7 days after coronary artery ligation in rats by the stable prostacyclin analogue iloprost. 242 67

The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Iloprost (0.1-100 microM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Iloprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5a in each of the groups was control 13.3 +/- 1.8 units/g tissue (n = 12) and iloprost 6.5 +/- 0.9 units/g (n = 12), p less than 0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 +/- 3.1% of the area at risk (n = 15) compared with 42.4 +/- 3.3% of control (n = 13), p less than 0.01. Iloprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the interface between infarcted and noninfarcted tissue: control (n = 9) 9.0 +/- 1.8 units/g tissue, iloprost (n = 6) 2.0 +/- 0.4 units/g, p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart. 243 29

Myocardial ischemia leads to the damage of cellular membranes and release of intracellular enzymes. We studied the influence of the prostacyclin analog, iloprost, on alterations in membrane phospholipid content and composition in rat myocardium during ischemia. Infusion of iloprost (100 ng/kg/min) or its vehicle started 20 min after coronary artery ligation, and the hearts were analyzed after 6 h. Myocardial creatine kinase activity was significantly reduced by approximately 25% in the ischemic areas of hearts from rats receiving vehicle. This reduction in myocardial creatine kinase activity was totally abolished by infusion of iloprost. Total phospholipid content was significantly reduced by 10% in ischemic areas of hearts obtained from vehicle infused animals. Iloprost infusion also prevented the loss of total phospholipids in the ischemic areas. The data show that coronary artery ligation is associated with a significant loss of total membrane phospholipids in ischemic regions of rat myocardium, characterized by significant decreases in phosphatidylcholine, phosphatidylethanolamine and cardiolipin. The decrease in cardiac phosphatidylcholine and phosphatidylethanolamine content was prevented by iloprost, whereas the decrease in cardiolipin content was unaltered. Infusion of the prostacyclin analog iloprost almost totally inhibited the ischemia induced loss of phospholipids, suggesting that this may be an important component of its cytoprotective mechanism of action.
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PMID:Protective actions of a stable prostacyclin analog in ischemia induced membrane damage in rat myocardium. 243 96

The effect of the prostacyclin-mimetic, iloprost, on the reversibly damaged ("stunned") myocardium was studied in barbital-anesthetized, open-chest dogs subjected to 15 minutes of coronary artery occlusion and 3 hours of reperfusion. Regional myocardial segment shortening (%SS) was measured in the subendocardium of nonischemic and ischemic-reperfused areas by sonomicrometry. Iloprost was infused for 30 minutes beginning 15 minutes prior to occlusion (0.05 microgram/kg/min, ILO-LOW, or 0.1 microgram/kg/min, ILO-HIGH) or immediately prior to reperfusion (0.1 microgram/kg/min, ILO-REP). %SS in the ischemic-reperfused region recovered to 3% of pretreatment values in the control (saline-treated) group by 3 hours of reperfusion. In contrast, %SS in the iloprost-treated groups was significantly enhanced versus the control group at all times of reperfusion. At 3 hours of reperfusion, %SS recovered to 43% (ILO-LOW), 58% (ILO-HIGH), and 35% (ILO-REP) of pretreatment values. The beneficial effect on functional recovery was significantly greater when iloprost was administered before occlusion versus immediately prior to reperfusion. Thus, part of the salutory effects of iloprost appear to occur prior to and/or during ischemia. Iloprost did not improve collateral blood flow to the ischemic region or myocardial high energy phosphate content at 3 hours of reperfusion. While iloprost significantly decreased mean arterial pressure during ischemia and early reperfusion, the hypotensive action did not appear to play a role in the amelioration of postischemic dysfunction, as preocclusion treatment with an equihypotensive dose of sodium nitroprusside produced no significant effect on postischemic recovery beyond 5 minutes of reperfusion. Results of in vitro experiments indicated that iloprost had no effect on the xanthine oxidase free-radical generating system including lipid peroxidation. However, iloprost decreased the neutrophil-derived superoxide burst after chemotactic stimulation. This beneficial action may, in part, explain the efficacy of iloprost in enhancing postischemic function of the stunned myocardium.
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PMID:Beneficial effects of iloprost in the stunned canine myocardium. 244 57


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