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)

The ability of the prostacyclin analogue iloprost to improve survival of ischemic experimental skin flaps was investigated. Unilateral island skin flaps based on the superficial inferior epigastric vessels were raised in 70 rats and subjected to varying lengths of primary ischemia. The flaps were divided into the following four groups: group I, no perfusion washout; group II, postischemic washout with lactated Ringer's solution; group III, postischemic washout with urokinase; and group IV, postischemic washout with iloprost. Flap survival rates for group IV were significantly higher than all other groups (p < 0.05). The primary ischemia time at which 50% of the flaps failed was 8.9 hours for group I, 9.5 hours for group II, 13.3 hours for group III, and 15.3 hours for group IV. This is the first study to investigate the effect of iloprost on skin flap survival. Iloprost was found to be significantly more effective than urokinase in salvaging ischemic experimental skin flaps.
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PMID:Iloprost improves survival of ischemic experimental skin flaps. 752 Feb 20

The effects of intravenous administration of iloprost, a prostacyclin analogue, on myocardial energy metabolism and myocardial blood flow (MBF) were examined in anesthetized open-chest dogs subjected to 60 min of myocardial ischemia by coronary ligation. Iloprost administration at levels of 0.1 or 0.2 micrograms/kg/min was started 30 min before the commencement of ischemia and continued throughout the 90 min observation period. Since systolic aortic pressure in the iloprost 0.2 micrograms/kg/min group showed significantly lower values than that in the control group, whereas no clear effect was observed with the lower concentration (0.1 micrograms/kg/min), this latter group was further investigated. This 0.1 microgram/kg/min dose of iloprost lacked influence on MBF in both ischemic and nonischemic areas but did result in a significantly higher value for high energy phosphate contents in the ischemic myocardium. Moreover, myocardial mitochondrial respiratory function in the ischemic area was significantly improved. These results indicate that iloprost brought about preservation of myocardial energy metabolism without alteration of coronary perfusion, suggesting that it may exert a direct cardioprotective effect.
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PMID:Beneficial effects of iloprost on acute myocardial ischemia in dogs. 753 70

Iloprost, a stable prostacyclin analogue, significantly enhances the survival of an axial-pattern groin flap in rats after ischemia-reperfusion. Treated flaps showed viability over 90 percent of their area 7 days after an 8-hour ischemic episode, whereas the saline-treated controls were viable over only 20 percent of their area (p = 0.002). This effect was seen at a low (10 ng/kg) dosage, and no apparent side effects were noted.
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PMID:Iloprost enhances survival of axial-pattern skin flaps in an ischemia-reperfusion model. 753 36

Endothelial cells modulate the tone of the underlying smooth muscle by generating endothelium-derived relaxing and constricting factors. Captopril (CPT), unlike other angiotensin-converting enzyme (ACE) inhibitors, contains a sulfhydryl (-SH) group and can act as a free radical scavenger. Iloprost (ILO) is a synthetic analogue of prostacyclin and mimics the effects of this compound. This study was designed to investigate the effect of ILO and CPT on the mechanism of endothelin (ET) release after mesenteric ischemia-reperfusion (I/R) injury in the rat. Sprague-Dawley rats were divided into five groups: sham-operated, control, ILO (25 micrograms/kg), CPT (10 micrograms/kg), and ILO + CPT. The superior mesenteric artery was occluded for 30 min and then allowed 90 min of reperfusion, except in the sham-operated group, and the corresponding agents were given to the treated groups prior to I/R injury. After I/R injury, portal venous blood was obtained for ET assay, and ileal tissue samples were also obtained for the determination of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) and for histopathological examination. MDA levels were significantly lower in the CPT, ILO and, ILO + CPT groups than in the control group, indicating the inhibition of lipid peroxidation in all groups. ET levels increased in the control group, and this increase was reversed with ILO. In the CPT group, ET levels were significantly increased, and the addition of ILO did not affect this increase. Significant cytopreservative effect was achieved with ILO and CPT, the latter being more prominent histopathologically. CPT exerts a significant protective effect on the intestinal mucosa after I/R injury. This protection is accomplished by increased ET levels and seems to be unrelated to its inhibitory effect on lipid peroxidation and also unrelated to the arachidonic acid cascade.
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PMID:Captopril increases endothelin serum concentrations and preserves intestinal mucosa after mesenteric ischemia-reperfusion injury. 753 37

In order to clarify interactions between the various endothelial vasoactive substances, the authors studied the behaviour of endothelin plasma levels during acute iloprost infusion in 7 elderly patients with critical leg ischemia. Iloprost was administered i.v., diluted in saline solution (200 ng/ml, from 30 to 40 ml/h, for 6 hours/day over 4 weeks). Endothelin was assayed in plasma on day 4 of treatment at times 0, 2, 4, 6, 8, hours, or in other words before treatment and ten every 2 hours up until the 6th hour, and then 2 hours after the end of iloprost infusion. The control group consisted of 7 age-matched subjects suffering from peripheral obliterating arterial disease at Fontaine's stage 1 and 2 who where infused with saline solution alone. Patients receiving iloprost presented a mean endothelin plasma level +/- SD at time 0 of 5.40 +/- 1.23 pg/ml, 4.24 +/- 0.72 pg/ml at time 2, 4.22 +/- 0.74 pg/ml at time 4, 4.24 +/- 0.22 pg/ml at time 6, and 4.49 +/- 0.58 pg/ml at time 8. The difference between endothelin levels in basal conditions and those at time 2, 4 and 6 was statistically significant. The difference between the peptide at times 0 and 8 was not statistically significant. In the control group the mean +/- SD of endothelin plasma level was, at the same times, respectively 5.23 +/- 0.55 pg/ml, 4.88 +/- 1.39 pg/ml, 5.44 +/- 1.51 pg/ml, 5.10 +/- 0.86 pg/ml and 5.60 +/- 1.64 pg/ml. The difference between endothelin levels in basal conditions and those at later times was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Behavior of endothelin plasma levels during iloprost infusion in patients with severe ischemia in the lower extremities]. 756 38

Effects of iloprost, which is a stable prostacyclin analogue, on the ischemic myocardium were examined in the open-chest dog heart in terms of biochemical parameters. Ischemia was initiated by ligating the left anterior descending coronary artery. When the coronary artery was ligated for 3 min, the levels or glycogen, fructose-1,6-diphosphate (FDP), adenosine triphosphate and creatine phosphate decreased, and the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), lactate, adenosine diphosphate and adenosine monophosphate increased. During ischemia, therefore, energy charge potential was significantly decreased from 0.89 +/- 0.01 to 0.82 +/- 0.01, and ([G6P] + [F6P])/[FDP] and [lactate]/[pyruvate] ratios were significantly increased from 1.75 +/- 0.30 to 29.05 +/- 5.70 and 13 +/- 3 to 393 +/- 112, respectively. Iloprost (0.1, 0.3, or 1 microgram.kg-1) was injected intravenously 5 min before the onset of ischemia. Iloprost (0.1, 0.3, and 1 micrograms.kg-1) reduced the ischemia-induced decrease in energy charge potential to 94, 74, and 86%, respectively, the increase in ([G6P] + [F6P])/[FDP] to 38, 29, 32%, respectively, and the increase in [lactate]/[pyruvate] to 67, 45, 65%, respectively. These results suggest that iloprost lessens the myocardial metabolic derangements produced by ischemia, and the most potent effect was obtained at the dose of 0.3 microgram.kg-1.
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PMID:Effects of iloprost, a PGI2 derivative, on ischemic myocardial energy and carbohydrate metabolism in dogs. 768 Nov 40

In the natural history of patients with peripheral obliterative arterial disease (POAD) the prognosis of the complaint "intermittent claudication" is relatively good and the amputation rate is presently only about 3%. However, POAD patients carry a high risk of cardiovascular events and their cumultative mortality rate within 10 years is as high as 40-50%. Atherothrombotic events in the coronary and, less frequently, cerebral arteries are by far the first cause of death and disability in these patients. The rationale for antithrombotic drugs in the treatment of POAD lies in the pivotal role of platelet activation and thrombin formation in the evolution of the atherothrombotic lesions, but also in the effect of some of these drugs on the regulation of microcirculatory responses. In acute thrombotic arterial occlusion, Heparin is the "first application" drug, especially in support of interventional revascularisation procedures. Regional thrombolysis often coupled with angioplasty (PTA), or systemic thrombolysis, are effective in revascularisation of especially infrainguinal-supra popliteal occlusions. However, controlled clinical trials are needed. In chronic POAD, intermittent claudication can be improved with a rational walking exercise programme, but, besides pentoxyphilline, especially ticlopidine significantly adds to the benefits of exercise. Regarding districtual progression of atherothrombosis and especially cardiovascular events, both aspirin and ticlopidine have been shown effective in single studies or meta-analyses. In a recent observational study of pooled data the cumulative endpoint including myocardial infarction, stroke and vascular death was reduced by 25 +/- 10% in the generality of patients treated with antiplatelet drugs. Finally, in critical limbs ischemia (CLI), some prostanoid compounds as Iloprost and Prostaglandin E1 favourably influence rest pain and ulcer healing, but less evidence is available on their effects on hard events as amputation and death. In conclusion, following the general indication to "be conservative" in the treatment of these patients, it seems clear that antithrombotic drugs have become by far a key medication in all different phases of POAD.
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PMID:Antithrombotic drugs in peripheral obliterative arterial diseases. 795 59

Several forms of cardiac adaptation to stress are known, differing in the evoking stress, in the time needed for adaptation and in the duration of the protective effect. A delayed adaptation produced a late appearing, prolonged protection against consequences of ischemia, such as early morphological changes, early and late postocclusion and reperfusion arrhythmias due to coronary artery occlusion or ouabain intoxication. Delayed adaptation was evoked by ischemic stress (repeated brief periods of rapid cardiac pacing or brief coronary occlusions) or by drugs (prostaglandin I2 and its stable derivatives). The protection produced by delayed adaptation proved to be time- and dose-dependent. Optimal effects appeared 24 to 48 h after treatment with an optimal dose of 50 microg/kg 7-oxo-prostacyclin or 10 microg/kg Iloprost. It is suggested that the mechanism of delayed cardioprotection is based on the fact that the stress-evoking adaptation stimulates the adenylate-cyclase/cyclic adenosine monophosphate (cAMP) system; the resulting elevation of cardiac cAMP level triggers the induction of some key enzymes such as Na/K-ATPase and phosphodiesterase (PDE) isoforms I and IV. Increased amount and activity of Na/K-ATPase accounts for preservation of normal membrane function and moderation of ischemic loss of potassium, and accumulation of sodium and calcium in the myocardium, as well as for reduced ouabain toxicity. The detrimental consequences of heavy stress-induced accumulation of cAMP in the heart are mitigated by hydrolysis of the latter, carried out by an enhanced amount and activity of PDE isoforms. Response to beta-adrenergic stimuli is also attenuated. In addition, electrophysiological changes such as prolongation of the effective refractory period and of the action potential duration may attenuate arrhythmias due to ischemia and reperfusion.
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PMID:On the mechanism and possible therapeutic application of delayed cardiac adaptation to stress. 860 40

To determine whether the prostacyclin analog iloprost plays a beneficial role in crystalloid cardioplegia in isolated working rat hearts, 20 isolated rat hearts were studied after sustaining 90 min of cardioplegic arrest under hypothermia (20 degrees C). The findings indicated that thromboxane A2 (TXA2) levels in coronary effluent were increased during reperfusion. Iloprost (12 nm/l) inhibited the release of TXA2 and improved the recovery of cardiac hemodynamics after ischemia. These data demonstrated that cardiac-derived TXA2 appeared to mediate reperfusion injury after prolonged aortic clamp or cardiac transplantation and iloprost cardioplegic infusion resulted in the inhibition of release of cardiac-derived TXA2 and in a better preservation of cardiac function after ischemic arrest.
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PMID:Beneficial effects of iloprost cardioplegia in ischemic arrest in isolated working rat heart. 880 25

Patients with heparin-induced thrombocytopenia (HIT) require an alternative antithrombotic treatment to heparin during arterial reconstruction. Ancrod and Iloprost have been employed but are not readily available and carry the risks of systemic side effects (depletion of fibrinogen, hypotension). A patient with HIT in whom intraoperative intraarterial urokinase (UK) was successfully utilized to enable safe arterial reconstruction is described. An 80 year old white female with diffuse arteriosclerotic cardiovascular disease and multiple vascular reconstructions had thrombotic complications following use for heparin during two of her prior operations associated with documented thrombocytopenia and anti-platelet antibodies. She presented with limb-threatening ischemia which was evaluated with angiography revealing severe stenosis of the proximal left superficial femoral artery, occlusion of both anterior tibial and peroneal arteries and several digital vessels, with intact posterior tibial runoff. A common femoral to mid-superficial femoral artery bypass was performed, utilizing contralateral reversed greater saphenous vein, while being treated with aspirin and a continuous intravenous infusion of low molecular weight dextran. During the procedure the clamped arteries were locally perfused with a high volume of dilute UK solution to prevent blood stasis, and enable local delivery of a thrombolytic agent. Although clot formation was observed in the operative field, none occurred within the clamped arteries. A total of 191,200 units of UK were employed with no bleeding complications. Following surgery the patient had a palpable pedal pulse and markedly improved perfusion of her toes. She was discharged on aspirin and coumadin on postoperative day five. It is concluded that for patients with HIT, systemic aspirin and dextran combined with local intraarterial UK are a simple and effective substitute for systemic anticoagulation with heparin during arterial reconstruction.
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PMID:Intraoperative urokinase as an alternative to heparin for patients with suspected heparin-induced thrombocytopenia requiring arterial reconstruction: report of a case and review of the literature. 894 86


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