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

Surgical revascularization as the initial therapy in acute lower limb ischemia (ALLI) is associated with a high cumulative mortality and amputation rate. Catheter-directed delivery of low-dose thrombolytic agents (intra-arterial thrombolysis, IAT) offers the possibility for a gentle revascularization with a minimum of stress for the patients. In two randomized studies, the primary rates of revascularization, amputation, and mortality did not differ significantly between IAT and surgical revascularization. However, in one study the 6-month event-free survival rate was 85% in the IAT group, and 63% in the surgical group. Also in the second study the 12-month results were significantly better in the IAT group (event-free survival 75%) than in the surgical group (event free survival 52%). The high-dose urokinase regimen recommended by some authors in IAT is associated with an unacceptable cerebral bleeding rate of up to 2%. Low-dose recombinant tissue-type plasminogen activator (rt-PA) (0.02 to 0.05 mg/h) is the most suitable agent in IAT because of rapid lysis and low bleeding complications. Patients with ALLI, classified as viable or threatened without neurologic deficit, benefit most from the IAT as the initial therapy in ALLI. When IAT is performed as the initial therapy in ALLI, surgical intervention becomes unnecessary in approximately one-third of the patients. In another third the subsequent correction of the cause of the ALLI can be performed electively, which reduces mortality and morbidity rates.
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PMID:Thrombolytic therapy in acute lower limb ischemia. 871 91

Data on the feasibility, safety, and clinical outcome of intracoronary stenting in acute myocardial infarction (AMI) are limited. This study examined the immediate angiographic results and the early and late outcomes in 32 patients who had stenting during AMI. Coronary angiograms recorded at the time of stenting were reviewed with quantitative measurements obtained on the "target" coronary lesion before and after stenting. Immediate angiographic success was achieved in 30 patients (94%). The minimal luminal diameter increased from 0.36 +/- 0.37 to 2.58 +/- 0.41 mm (p<0.0001). Two patients died in the hospital. Of the remainder, none had reinfarction or required bypass surgery, whereas 2 required repeat coronary angioplasty for recurrent ischemia. Although thrombus at the infarct-related coronary lesion was initially detected in 41% of the patients, its presence was not associated with adverse procedural outcome. Only 1 patient had persistent thrombus after stenting, which resolved with intracoronary urokinase. At a mean follow-up of 6.1 +/- 4.1 months, there was 1 additional cardiac death, and no patient had AMI or required repeat coronary angioplasty or bypass; among the 29 survivors, 86% were free of angina. Thus, intracoronary stenting of the infarct-related artery in the setting of AMI is associated with excellent immediate angiographic success and a favorable clinical outcome, and remains an option even in the presence of thrombus.
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PMID:Usefulness of intracoronary stenting in acute myocardial infarction. 871 34

The role of thrombolysis in reestablishing patency in the microcirculation following ischemia, and thereby improving the efficacy of agents attenuating reperfusion injury, such as the oxygen free radical scavenger, superoxide dismutase (SOD), was investigated in a rat model. Abdominal skin flaps were subjected to normothermic ischemia induced by complete occlusion of the pedicle for periods of 12, 13, 14, 16, 18, 20, 22, and 24 hr. In Group 1 (n = 64), all animals received flap washout using 100,000U urokinase (manual injection) followed by 7,500 IU SOD given intra-arterially immediately prior to reperfusion. Animals in Group 2 received flap washout consisting of 100,000U urokinase given via a pressurized delivery system, followed by 7,500 IU SOD. Results demonstrated a statistically significant improvement in flap survival in Group 2. The authors concluded that thrombolytic therapy may be useful in improving the delivery of agents, such as SOD, which attenuate reperfusion injury in skin flaps.
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PMID:Thrombolysis at a controlled pressure prolongs the survival of skin flaps treated with superoxide dismutase. 872 41

Microvascular thrombosis is known to play an important part in the cessation of flow seen in a flap following ischemia and revascularization. Its reversal, using thrombolytic therapy, is associated with higher rates of successful flap salvage. Although this procedure restores patency to the microcirculation, the damaged endothelial cell layer remains highly thrombogenic and a definite risk of rethrombosis exists in the early period of reperfusion. In an inferior epigastric flap model in a rat, we investigated the effect of additional heparin (subcutaneous and intravenous administration) following a standardized urokinase washout (100,000 iu) of the ischemic flaps. Flap survival was assessed at 1 week and morphological changes in the microcirculation were observed using electron microscopy. Results showed a significant increase in flap survival in the group receiving intravenous heparin following urokinase washout and suggest that systemic heparin may play a beneficial role in the early reperfusion period following thrombolytic flap salvage.
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PMID:Additional benefit of heparin in the thrombolytic salvage of ischemic skin flaps. 874 44

Therapy for stroke is undergoing major changes. Many of the changes parallel the advances made in the therapy for myocardial infarction. Acute intervention with cytoprotective and thrombolytic agents is undergoing active investigation. Cytoprotective therapy includes drugs that act to prevent cell death during ischemia and reperfusion. These agents include calpain inhibitors, voltage-sensitive calcium- and sodium-channel antagonists, receptor-mediated calcium-channel antagonists [including N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) antagonists], glutamate-synthesis inhibitors, glutamate-release antagonists, gamma-aminobenzoic acid (GABA) antagonists, 5-HT (serotonin) receptor agonists, gangliosides, antioxidants, growth factors, antiapoptotic agents, and antiadhesion molecules. Thrombolysis is effective in myocardial infarction. Thrombolysis is undergoing evaluation in stroke with streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC), tissue plasminogen activator (t-PA; including recombinant t-PA), urokinase, and single-chain urokinase (scu-PA). Both systemic and selective administration are being evaluated. Preventive therapy with both antiplatelet and anticoagulant drugs sheds new light on how best to stratify patients in terms of a risk-benefit ratio. Continuing public education will be essential as stroke therapy advances.
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PMID:Medical therapy for ischemic stroke. 877 66

The failing free flap remains a major problem for the reconstructive surgeon. Many and varied pharmacologic agents have been utilized to reverse the effects of ischemia in these flaps. Treatments have been aimed at inhibiting presumed causative factors in the no-reflow phenomenon. Therapy has generally been single in nature and designed to affect only one of these presumed factors. In this study, several pharmacologic agents were utilized individually or in combination therapy as postischemic washouts, in an effort to attack the multiple causative factors in the no-reflow phenomenon and to improve flap survival in a rat abdominal skin flap model. The treatment agents included lactated Ringer's, superoxide dismutase, and urokinase, with each used independently as a postischemic perfusion washout. Combination therapy utilized an initial postischemic perfusion with urokinase, followed by a second perfusion washout with superoxide dismutase. After 18 hr of primary ischemia, there was increased flap survival in the animals undergoing perfusion washout with either superoxide dismutase alone or with combined urokinase and superoxide dismutase washouts, compared to all other treatments (p < 0.001). It was found that flaps undergoing combined urokinase and superoxide dismutase postischemic perfusion washouts demonstrated significantly improved survival after 20 hr of primary ischemia, compared to all other therapies (p < 0.05). By demonstrating improved survival when a thrombolytic agent is used in conjunction with an oxygen free radical scavenger, these findings may have implications in the treatment of clinically failing free flaps.
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PMID:Combination therapy for salvaging a failing, experimental skin flap. 886 75

Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-alpha, IL-1-alpha and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-alpha, IL-1-alpha) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.
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PMID:Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain. 889 62

Impending gangrene of the hand or digits secondary to palmar or digital artery occlusion can be a devastating complication of upper extremity thromboembolic or atheroembolic disease. Over the past 7 years, 9 patients with severe unilateral hand ischemia and impending tissue loss secondary to distal forearm, palmar arch, and digital artery occlusion were managed with intra-arterial urokinase (UK) infusion. The etiology of the ischemia was thromboembolism in 3 patients, atheroembolism in 2, and traumatic ulnar artery occlusion ("hypothenar hammer syndrome") in the remaining 4 patients. Initial high-dose UK was administered in 3 patients (240,000 U per hour for 2 hours) and all 9 patients were maintained on 80,000 to 120,000 U per hour until clot lysis occurred or until a minimum dose of 600,000 U had been given without clinical improvement. Following UK therapy, the 3 patients with thromboemboli had angiographic demonstration of clot lysis as well as complete resolution of ischemia. The 2 patients with atheroemboli showed no angiographic or clinical improvement, and both required surgical intervention. Angiographic improvement was demonstrated in only 1 patient with traumatic ulnar artery occlusion, although 3 of the 4 patients were clinically improved. A pericatheter thrombosis due to insufficient heparinization and a subcutaneous abscess at the femoral artery puncture site were the only complications of UK infusion. No hemorrhagic complications occurred and no adverse effects of lytic therapy were documented in patients who subsequently required surgery. UK is an effective treatment for recent thromboembolism, because it lyses unorganized thrombi. It is ineffective for treatment of organized thrombi or atheroemboli. Because the etiology of acute hand ischemia is not always obvious at the time of presentation, a trial of UK infusion is warranted, because it is relatively safe and its use may obviate the need for complex microsurgical reconstruction.
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PMID:The use of intra-arterial urokinase in the management of hand ischemia secondary to palmar and digital arterial occlusion. 890 42

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

A 4-month randomized placebo controlled trial on urokinase therapy in 36 consecutive systemic sclerosis patients randomly treated with urokinase or placebo was conducted. While patients on placebo did not show any significant improvement, in those following urokinase therapy there was a noticeable improvement in skin sclerosis observed via hand-print and ultrasonography of the skin. Vascular involvement improved: this was demonstrated by capillaroscopy results, showing an improvement in pattern and signs of revascularization and the resolution of skin ulcers. Vascular damage is a typical occurrence in systemic sclerosis cases and various vasoactive drugs are used symptoms for some such as Raynaud's syndrome or skin ulcers. At the moment these drugs seem to constitute the most effective therapy, and have few side effects. We have found only one previous study utilizing urokinase therapy for acute digital ischemia in systemic sclerosis. Our study is the first in which urokinase therapy has been used for the treatment of systemic sclerosis in a large number of patients.
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PMID:A placebo-controlled study on urokinase therapy in systemic sclerosis. 895 56


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