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)

Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.
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PMID:Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery. 9 90

We have tested the feasibility of local intraarterial thrombolytic therapy in ischemic stroke in the carotid artery territories observed within 5 h of the onset of symptoms. Only 5 of 615 consecutive patients were enrolled. They were 1 man and 4 women aged 50 to 75 years. Angiography disclosed occlusion of the M2 tract in one, of the M3 tract in one, of the carotid siphon in one of M4 tract in two. Intraarterial urokinase was infused at a mean dosage of 560,000 units close to the site of occlusion. Four of them had partial or complete recanalisation at early angiographic control and were independent at 6th month control. The one who did not demonstrate recanalisation was confined to a wheelchair. One patient, who had recanalisation, sustained a hemorrhagic transformation of the brain ischemia not interfering with outcome. Our experience, at the light of the low rate of enrollment, despite the results, suggest that intraarterial thrombolysis may be a therapeutic tool for selected patients with stroke in the carotid artery territories and not a routinary treatment for them.
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PMID:Local intraarterial thrombolysis for acute stroke in the carotid artery territories. 141 52

We tested the safety and the usefulness of intravenous urokinase (2 million units administered over 30 min) in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-h Holter monitoring (Phase 1) despite maximal medical therapy. After thrombolysis, recurrence of ischemia was observed during a week of observation in the CCU, including two 24-h Holter monitorings at the beginning and the end of the week (Phase 2). Seventeen patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 19 patients had refractory angina or a major cardiac event [10 patients underwent coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) for refractory angina (p less than 0.001), 6 other patients with refractory angina continued medical therapy, one patient had a myocardial infarction, and two patients died]. In Phase 1 the duration of total ischemia (min/24 h) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). In comparison to Phase 1, duration of total ischemia in Phase 2 was significantly reduced in both groups (16.9 +/- 19.6 vs. 25.4 +/- 17.7; p less than .001). A percent value expressing this variation was calculated for each patient: the variation thus obtained again gave information on the clinical outcome--the greater the reduction, the lower the risk of cardiac events (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic therapy in refractory unstable angina: the role of Holter monitoring. 167 54

We have studied the development of the collateral circulation in the heart in response to gradual and progressive coronary artery occlusion. When the coronary stenosis becomes critical, tissue ischemia occurs, which we believe leads to the production (and probably to release from storage sites) of tissue hormones (mitogens) that lead to mitosis of endothelial and smooth muscle cells. We have identified from hearts several known mitogens (aFGF, bFGF), non-mitogenic angiogenic factors (TGF-beta), a new anti-mitogen, and a new myocyte-derived growth factor (structures of the last two not yet elucidated). An important principle in the development of collaterals is the remodeling of pre-existing small vessels into the much larger vascular structure. To accommodate new cells old structures have to be removed by controlled proteolysis (tPA, uPA, elastase).
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PMID:Angiogenesis in the adult heart. 171 53

Intracoronary (i.c.) thrombus is a frequent finding in patients with unstable angina (UA). Accordingly, thrombolytic treatment could be beneficial, as resolution of thrombus might result in increased delivery of blood flow to the ischemic regions. To test this hypothesis, we studied 13 patients with active UA and ST-segment shift in the anterior leads. Coronary angiography was performed and great cardiac vein blood flow (GCVF; thermodilution) was measured in all patients 25 +/- 14 h after the last chest pain episode. Following angiography, patients received i.v. urokinase (UK: 1,000,000 IU/30 min); aortic pressure and GCVF were measured before and every 10 min following drug infusion, for a total time of 90 min. At baseline angiography, 5 of 13 patients (Group 1) had evidence of i.c. thrombus (intraluminal filling defect or thrombotic subocclusion) in the ischemia-related left coronary artery, whereas 8 patients (Group 2) did not. Group analysis showed that UK increased GCVF and decreased anterior coronary resistance in Group 1 (respectively, from 86 +/- 33 to 114 +/- 41 ml/min: p less than 0.005; and from 1.37 +/- 0.68 to 1.01 +/- 0.44 mmHg/ml/min: p less than 0.05) but not in Group 2 (both: p = NS). In conclusion, UK has been shown to increase regional coronary blood flow in selected patients presenting with active UA, as well as evidence of i.c. thrombus at early angiography. Heterogeneity of angiographic findings could explain controversies in trials dealing with thrombolysis in UA.
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PMID:Coronary hemodynamic effects of systemic thrombolysis in patients with unstable angina. 173 10

The main cause of death in Kawasaki disease is myocardial infarction due to thrombotic occlusion of a coronary aneurysm. Intracoronary thrombolytic treatment was performed in 15 patients with Kawasaki disease with giant coronary aneurysms. Three patients had acute myocardial infarction, four demonstrated silent myocardial infarction, three suffered chest pain and five did not show ischemia features but had massive thrombus in the coronary aneurysms. Urokinase was infused into the coronary aneurysms as a bolus of 8,000 to 10,000 units/kg via a catheter over 10 minutes. Partial but significant coronary recanalization was achieved after injection of urokinase in a patient with acute myocardial infarction. Complete resolution of massive intracoronary thrombi was observed in 3 of 15 patents, and partial resolution was recognized in 4 cases. In 7 patients, the size of thrombus did not change. Recurrence of the thrombus was observed in 4 patients by serial two-dimensional echocardiography. Urokinase was readministered and two showed significant reduction in the thrombus. All patients have been followed for more than 2 years with longest 8 years (mean: 3.3 yrs), and none have had a recurrence of myocardial infarction or died. These findings suggest that intracoronary urokinase is useful for the treatment and prevention of myocardial infarction in Kawasaki disease.
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PMID:Intracoronary urokinase in Kawasaki disease: treatment and prevention of myocardial infarction. 185 11

All complications occurring in 55 local thrombolytic infusions performed for (sub)acute limb ischemia using streptokinase (SK) in 22 procedures and urokinase (UK) in 33 procedures were recorded. Success was achieved in 74.5% of the procedures. Major complications occurred in 31.8% of the procedures using SK, and in 12.1% of the procedures using UK (p = 0.07). Hemorrhage was the most common major complication and occurred in 27.2% of SK procedures and in 9.0% of UK procedures, a difference which was not significant. Overall, 30 day mortality was 16.3% and procedure-related death was 1.8%. Moderate complications necessitating only the adjustment of drug regimen and minor complications without consequence were observed in 45.5% and 45.5%, respectively, of the SK procedures, and in 57.6% and 66.7% of the UK procedures.
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PMID:Percutaneous local arterial thrombolytic infusion. Therapeutic effects and complications. 186 1

The immediate and delayed effects of urokinase and heparin on minimal cross-sectional area of a patent ischemia-producing coronary artery were prospectively investigated in 43 patients with unstable angina. After baseline angiography, patients were randomized to 3 different treatment groups: group I--urokinase (1,000,000 U intravenous bolus dose), followed by heparin infusion 3 hours later; group II--heparin (10,000 U intravenous bolus, followed by continuous infusion); and group III--conventional therapy only (intravenous nitroglycerin, beta blockers and calcium antagonists). Angiography was repeated at 1 hour and at 8 days of treatment and minimal cross-sectional area was determined in the 35 patients who completed the study. In group I, minimal cross-sectional area increased from 0.84 +/- 0.48 mm2 at baseline to 0.94 +/- 0.49 mm2 at 1 hour (p less than 0.05), and to 1.00 +/- 0.51 mm2 at 8 days (p less than 0.01 vs baseline). In group II, a significant increase in minimal cross-sectional area was observed only at the 8-day angiography (0.64 +/- 0.39 mm2 at baseline; 0.67 +/- 0.37 mm2 at 1 hour [p = not significant]; and 0.79 +/- 0.48 mm2 at 8 days [p less than 0.01] vs baseline). In group III, no significant changes in minimal cross-sectional area occurred either at 1 hour or at 8 days. Thus, both urokinase and heparin improved lesion geometry in patients with unstable angina, although a large individual variation was noticed. The effect occurred earlier with urokinase than with heparin.
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PMID:Effects of urokinase and heparin on minimal cross-sectional area of the culprit narrowing in unstable angina pectoris. 187 70

Recent trials of myocardial reperfusion using single-agent thrombolytic therapy and sequential cardiac catheterization have supported a conservative approach to the patient with acute myocardial infarction. To evaluate combination thrombolytic therapy and the role of a previously untested strategy for the aggressive use of cardiac catheterization, we performed a multicenter clinical trial with a 3 x 2 factorial design in which 575 patients were randomly allocated to one of three drug regimens--tissue-type plasminogen activator (t-PA) (n = 191), urokinase (n = 190), or both (n = 194) - and one of two catheterization strategies--immediate catheterization with angioplasty for failed thrombolysis (n = 287) or deferred predischarge catheterization on days 5-10 (n = 288). Patients with contraindications to thrombolytic therapy, cardiogenic shock, or age of more than 75 years were excluded. Global left ventricular ejection fraction was well preserved and almost identical at predischarge catheterization (54%), regardless of the catheterization or thrombolytic strategy used (p = 0.98). Combination thrombolytic therapy was associated with a less complicated clinical course, most clearly documented by a lower rate of reocclusion (2%) compared with urokinase (7%) and t-PA (12%) (p = 0.04) and a lower rate of recurrent ischemia (25%) compared with urokinase (35%) and t-PA (31%). When a composite clinical end point (e.g., death, stroke, reinfarction, reocclusion, heart failure, or recurrent ischemia) was examined, combination thrombolytic therapy was associated with greater freedom from any adverse event (68%) compared with either single agent (urokinase, 55%; t-PA, 60%) (p = 0.04) and with a less complicated clinical course when the composite clinical end points were ranked according to clinical severity (p = 0.024). Early patency rates were greater with combination therapy, although predischarge patency rates after considering interventions to maintain patency were similar among drug regimens. No difference in bleeding complication rates was observed with any thrombolytic regimen. The aggressive catheterization strategy led to an overall early patency rate of 96% and a predischarge patency rate of 94% compared with a 90% predischarge patency in the conservative strategy (p = 0.065). The aggressive strategy improved regional wall motion in the infarct region (-2.16 SDs/chord) compared with deferred catheterization (-2.49 SDs/chord) (p = 0.004). More patients treated with the aggressive strategy were free from adverse outcomes (67% versus 55% in the conservative strategy, p = 0.004), and the clinical course was less complicated when the adverse outcomes were ranked according to severity (p = 0.016). No significant increase in use of blood products resulted from the aggressive strategy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction--phase 5 randomized trial. TAMI Study Group. 202 33

Intraarterial urokinase (IAUK) was administered to 33 patients on 40 occasions for the treatment of acute extremity ischemia and long-term patency was assessed. Lysis was successful in 39 of the 40 cases (95%). Occlusive thrombus was cleared in 12 of 13 patients with native artery occlusion (7 complete, 5 partial), 8 of 9 with autologous vein grafts (5 complete, 3 partial), and in all 18 patients with synthetic grafts (17 complete, 1 partial). The primary cumulative patency following successful IAUK was 100% for native arteries and 47% for synthetic grafts at 12 months, and 23% for autologous grafts at 9 months. The difference in rethrombosis rate between autologous vein (67%) and native artery (0%) was significant (p = 0.02) as was the difference between infrainguinal prosthetic grafts (63%) and native artery (p = 0.025). IAUK is most effective for the treatment of native artery occlusion, but is significantly less effective for thrombosed infrainguinal autologous vein or synthetic grafts due to the likelihood of reocclusion, despite the high immediate success rate. For autologous vein grafts, lysis is frequently incomplete and patency rapidly deteriorates regardless of adjunctive therapy to relieve the underlying obstruction.
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PMID:Outcome of intraarterial urokinase for acute vascular occlusion. 193 33


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