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)

Antithrombin (AT) supplementation in patients with severe sepsis has been shown to improve organ failures in which activated leukocytes are critically involved. However, the precise mechanism(s) for the therapeutic effects of AT is not well understood. We examined in rats whether AT reduces ischemia/reperfusion (I/R)-induced renal injury by inhibiting leukocyte activation. AT markedly reduced the I/R-induced renal dysfunction and histologic changes, whereas neither dansyl glutamylglycylarginyl chloromethyl ketone-treated factor Xa (DEGR-F.Xa), a selective inhibitor of thrombin generation, nor Trp49-modified AT, which lacks affinity for heparin, had any effect. Renal tissue levels of 6-keto-PGF(1 alpha), a stable metabolite of prostacyclin (PGI(2)), increased after renal I/R. AT enhanced the I/R-induced increases in renal tissue levels of 6-keto-PGF(1 alpha), whereas neither DEGR-F.Xa nor Trp49-modified AT had any effect. AT significantly inhibited I/R-induced decrease in renal tissue blood flow and the increase in the vascular permeability. Ischemia/reperfusion-induced increases in renal tissue levels of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and myeloperoxidase were significantly inhibited in animals given AT. Pretreatment of animals with indomethacin reversed the effects induced by AT. Iloprost, an analog of PGI(2), produced effects similar to those induced by AT. These observations strongly suggest that AT reduces the I/R-induced renal injury by inhibiting leukocyte activation. The therapeutic effects of AT might be mainly mediated by PGI(2) released from endothelial cells through interaction of AT with cell surface glycosaminoglycans.
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PMID:Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production. 2354 58

Spinal cord ischemia may develop into paraplegia in some cases during operation of the thoracoabdominal aorta. This is attributable to the vulnerability of spinal motor neurons to ischemia. In this study, iloprost was used as an agent to decrease the severity of ischemia and reperfusion injury to the spinal cord motor neurons. Twenty-one rabbits were randomized into three groups of seven animals each: group A (iloprost not administered), group B (25 ng/kg per minute iloprost), and group S (sham-operated). The spinal cord ischemia model was created by a 15-min occlusion of the aorta just caudal to the renal artery with a balloon catheter. Administration of iloprost began 10 min before occlusion of the aorta, and continued thereafter for 60 min. The pre- and postocclusion arterial pressure and heart rate recordings, results of blood gas analyses, and hematocrit and glucose levels were recorded. The spinal cords were removed after 8-h monitoring of neurologic function. Viable and nonviable motor neurons in the anterior horn of the spinal cord were counted under light microscopy. Any significant alteration in hemodynamics, blood gases, and other physiologic parameters could not be detected within the groups. Iloprost had a moderately hypotensive effect. Neurologic function in terms of Johnson scoring was significantly better in the iloprost group (P<0.05). The number of viable cells was higher, whereas the number of nonviable cells was lower in iloprost group, when compared with the control group (P<0.05). Higher numbers of viable motor neurons were consistent with the neurological findings. As a result of this study we concluded that iloprost infused during clamping of the aorta mitigates the spinal cord injury due to ischemia and reperfusion, and has a significant protective effect.
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PMID:Early protective effects of iloprost, a stable prostacyclin analog, during spinal cord ischemia in a rabbit model. 1577 81

The local ischemia-reperfusion (I/R) process gains a systemic nature and affects distal organs. The remote effects of I/R are most frequently observed in the lungs and pulmonary damage may vary from acute lung injury with mild dysfunction to severe respiratory failure or the acute respiratory distress syndrome. In this hind limb I/R induced experimental lung injury model two groups of rats as IR and ILO were determined. Both groups underwent 60 min of ischemia and 120 min of reperfusion. While ILO group received iloprost in saline, IR group received only saline before reperfusion period intravenously. Serum myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels and total antioxidant capacity (TAC) and lung tissue MPO activity, MDA levels and Na+-K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The MPO activities in serum and lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01). The MDA levels in lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01), but the decreases were not significant in serum MDA levels (P=0.052). Serum TAC and lung tissue Na+-K+ ATPase activity levels were found to be increased in ILO group compared to IR group (P < or = 0.01). Lung histology showed marked improvement by iloprost compared to the IR group in this study. Iloprost has been found to be effective in attenuating ischemia reperfusion-induced remote organ damage, in this case, lung injury, in rats.
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PMID:The influence of iloprost on acute lung injury induced by hind limb ischemia-reperfusion in rats. 1577 6

Iloprost, a stable prostacyclin analogue, regulates expression of genes that are involved in inflammation and in cell growth and inhibits the in vitro production of cytokines. We evaluated the effect of an in vivo weekly iloprost treatment on TNF-alpha and IL6 monocyte production (evaluated by ELISA), on monocyte apoptosis (Annexin V/uptake of propidium iodide by flow cytometry) and on peripheral blood mononuclear cell (PBMC) TNF-alpha receptors (TNF-RI and TNF-RII) mRNA expression (RT-PCR) in 14 atherosclerotic critical limb ischemia patients. PBMC were stimulated with LPS for 24h. TNF-alpha production was significantly reduced by iloprost whereas IL6 production was not affected. Iloprost did not accelerate monocyte apoptosis. TNF-RI mRNA expression was not modified by iloprost, whereas TNF-RII mRNA expression was significantly reduced. Our data show that iloprost may have anti-inflammatory effects in addition to the well-known vasodilatatory and anti-aggregant ones.
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PMID:Iloprost treatment reduces TNF-alpha production and TNF-RII expression in critical limb ischemia patients without affecting IL6. 1609 91

Revascularization by either bypass surgery or endovascular recanalization is considered the first-choice treatment in patients with critical limb ischemia (CLI). Only conservative options are left in CLI patients in whom successful revascularization strategies are not possible: in these patients, at present, prostanoids (iloprost and prostaglandin [PGE1]) represent the pharmacological treatment of choice. Iloprost resulted more effective than PGE1, in a 6 month follow-up, in both limb savage and in prevention of cardiovascolar death, either in diabetic or non diabetic patients with unreconstructable CLI. In our experience, in patients who have responded to a first cycle of therapy (early responders), performed for at least 2-3 weeks, cyclic annual further treatments with iloprost are usually able to stabilize arterial disease, with a regression to Fontaine II stage and, in absence of further arterial complications, with complete limb preservation for an unlimited period of time. In non-responder patients, who are not urgently supposed to undergo amputation, a second cycle of iloprost carried out within few months from the first one, is able to increase the percentage of responders to prostanoids (late responders). Vice versa, in non-responders to repeat prostanoid cycles, it is useful to verify the outcomes of further attempts at saving, the symptomatic limb by surgical or endovascular re-timing, spinal cord stimulation, gene or stem cell therapy. Our recent better outcomes are related to earlier microvascular diagnosis and to earlier, repeat, pharmacological treatments with iloprost. Transcutaneous oxygen and carbon dioxide monitoring improves the possibility of an earlier diagnosis of microvascular damages and categorizes CLI patients in responders and non-responders after prostanoid treatments.
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PMID:[Medical therapy in critical lower limb ischemia when immediate revascularization is not feasible]. 1675 15

Iloprost, a prostacyclin analogue, is a treatment option for surgically unsuitable diabetic chronic critical limb ischemia (CLI), although its outcome is difficult to be anticipated clinically. Whether transcutaneous (tc) oxygen tension (PO2) predicts the response to iloprost in diabetic CLI is unclear at this point and, in that same context, the prognostic role of tc carbon dioxide tension (PCO2), another ischemia-sensitive parameter, is unknown. Supine and dependent tcPO2 and tcPCO2 were measured at baseline and after 4 weeks of iloprost treatment in 31 limbs of 26 type-2 diabetic angiopathies with CLI not amenable to surgery. Success was defined as pain relief and significant reduction of analgesics. Clinical outcome was stratified by baseline tcPO2 and tcPCO2 tertiles, and likelihood ratios (LR) quantified the increase from pretest chances given a certain result. Iloprost succeeded in 16 (52%) and failed in 15 limbs (48%) and post-treatment tcPO2 followed a parallel course. Failures increased by ascending baseline tcPCO2 and descending tcPO2 tertiles; successes behaved specularly. Predictions of failure based on elevated tcPCO2 (>53 mm Hg) were more efficient than relying on depressed tcPO2 (LR 10.7 vs 3.6); success was almost certain when tcPO2 was >23 mm Hg (LR = 17.8). Dependent determinations were less useful than supine measurements for prognostic use. Elevated tcPCO2 predicted failure efficiently and high tcPO2 was a useful prognostic tool for success of iloprost, suggesting that their combined use may allow better prognostic stratification and improve the therapeutic approach to diabetic CLI.
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PMID:Transcutaneous oxygen and carbon dioxide levels with iloprost administration in diabetic critical limb ischemia. 1695 24

Oxidative stress is involved in pathogenesis of Raynaud's phenomenon (RP), a hallmark of systemic sclerosis (SSc). Frequent episodes of ischemia-reperfusion may lead to release of free radicals and enhanced lipid peroxidation reflected by elevated levels of malondialdehyde (MDA). The failure of native antioxidants (Catalase [CAT], Superoxide dismutase [SOD], and Ceruloplasmin [CP]) might be crucial in endothelial cells damage in RP. Iloprost (IL) synthetic prostacyclin analogue is currently used in the treatment of SSc patients with RP. The objectives of this study were to compare the serum levels of MDA and CP, CAT and SOD activity in red blood cells hemolysate in SSc patients compared to healthy controls; and to study the effect of 5-days IL infusions on MDA and CP levels, and CAT and SOD activity in SSc patients with RP. Twelve SSc patients were treated with 50 mug IL for 5 days. Blood samples were taken before and after day 1st and after day 5th of IL infusions. Levels of CAT were measured according to the Aebi's method; SOD, according to the Misra and Fridovich method; MDA, according to Slater's method; and CP, according to Ravin's method. Activities of CAT (p < 0.001) and SOD (p < 0.04) were significantly reduced; levels of CP (p < 0.006) and MDA (p < 0.06) were raised in SSc compared to controls. IL infusions caused reduction in MDA (p < 0.0001) levels and enhanced production of SOD (p < 0.006) and CAT (p < 0.003). The levels of CP did not change (p = 0.48). Oxidant status in SSc patients with RP is impaired. Therapy with IL led to normalization of antioxidant activity. We suggest that CAT may be a sensitive and reliable laboratory marker of oxidative stress severity in RP. We found that IL, in addition to its vasoactive properties, has a potential to activate inner antioxidant system. Activation of inner antioxidant activity may explain long-term effect of IL instead of its very short half-life time.
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PMID:Antioxidant status after iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis. 1740 13

Systemic sclerosis is a connective tissue disease in which oxidative stress represents an important player among the complex pathogenetic mechanisms of the disease. Iloprost, an analogue of natural prostacyclin, is used in systemic sclerosis for the treatment of severe Raynaud's phenomenon and ischemic ulcers. There is a clear evidence that iloprost attenuates oxidative damage induced by ischemia-reperfusion phenomena. The aim of this study is to evaluate the effect of iloprost on oxidative status in ten patients with systemic sclerosis by measuring urinary levels of 8-isoprostaglandin-F(2alpha), a member of F(2)-isoprostanes. We found that systemic sclerosis patients cyclically treated with iloprost showed increased urinary level of 8-isoprostaglandin-F(2alpha )in comparison with healthy subjects; urinary 8-isoprostaglandin-F(2alpha) did not diminish soon after the iloprost infusion as well as 3, 15 and 30 days after the drug administration. Unlike experimental studies, in vivo the strong vasodilator effect of iloprost infusion did not reduce oxidative status.
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PMID:Iloprost infusion does not reduce oxidative stress in systemic sclerosis. 1770 20

The effects of iloprost on ischemia-reperfusion injury have been studied on the skeletal, muscle, liver, myocardium, kidney, and spinal cord. However, no sufficient data exist about effects of levosimendan on renal ischemia-reperfusion injury. The purpose of this experimental study was to investigate and compare effectiveness of levosimendan and iloprost on renal injury induced by ischemia and reperfusion. Fifty rabbits were divided into five groups. Levosimendan was continuously infused starting half an hour before the cross-clamp. Cross-clamp time was one hour. After one hour ischemia, levosimendan was continued for 4 h in Group A whereas Group B took iloprost in the same protocol. Group C was the control group which did not receive any medication. Group D was sham group and Group E was medicated both iloprost and levosimendan. Renal tissues were histologically and biochemically evaluated. The histological scores were obtained according to presence of tubular necrosis and atrophy, regenerative atypia, hydropic degeneration (Group A vs. Group C<0.001, Group B vs. Group C<0.001, Group D vs. Group C<0.01, Group E vs. Group C<0.001). Mean malondialdehyde levels were 114+/-12 nmol/g tissue; in Group A 121+/-13 nmol/g tissue, in Group B 134+/-13 nmol/g tissue, in Group E 130+/-11 nmol/g tissue, in Group D 134+/-11 nmol/g tissue (Group A vs. Group B; P=0.003, Group B vs. Group D; P=0.132, Group A vs. Group E; P=0.132). Malondialdehyde levels and histologic scores of all of the groups were significantly different from the control group. Iloprost and pentoxyfillin reduced renal ischemia-reperfusion injury in rabbit model. There was no significant difference between these two medications.
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PMID:The influence of levosimendan and iloprost on renal ischemia-reperfusion: an experimental study. 1805 54

Postconditioning (PostC), obtained with brief intermittent cycles of ischemia alternating with reperfusion applied after the ischemic event, has been shown to reduce infarct size. Recently, we have shown that PostC triggering includes B2 receptor activation and its downstream pathway. Moreover, we showed that BK intermittent infusion induces a cardioprotection similar to PostC. The aim of this study was to investigate the involvement of cyclooxygenase-(COX)-derivated prostaglandins, such as prostacyclin (PGI2) pathway in the cardioprotective action mediated by intermittent BK infusion. Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. Myocardial damage was evaluated using nitro-blue-tetrazolium staining. The production of metabolite of PGI2, 6-keto-PGF1alpha, was evaluated with EIA assay on the samples collected during reperfusion. The perfusion pressure and the left ventricular pressure were monitored. In Control hearts, the infarct size was 64% +/- 4% of risk area. PostC reduced significantly the infarct size (28% +/- 4% P < 0.001 Vs. Control). BK intermittent protocol to mimic PostC, attenuated infarct size (40% +/- 2% P < 0.01 Vs. Control). The BK-intermittent and PostC protections were abolished with COX-inhibition. Intermittent BK and PostC enhanced the release of prostacyclin metabolite, 6-keto-PGF1alpha, in the late phase of reperfusion (i.e., 6-keto-PGF1alpha peaked 30 min after protective maneuvers). Also the stable PGI2 analogue, Iloprost, given in the early reperfusion reduced infarct size and improved post-ischemic heart function. In conclusion, protection by PostC and intermittent BK requires COX activation and PGI2 release during late reperfusion. These data suggest that COX must not be inhibited to have PostC protection. This finding should be kept present by future clinical studies on PostC.
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PMID:Postconditioning and intermittent bradykinin induced cardioprotection require cyclooxygenase activation and prostacyclin release during reperfusion. 1818 93


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