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)

This study examines the cardioprotective effects of Na+/H+ exchange inhibition with BIIB-722 or ischemic preconditioning after occlusive thrombus formation and subsequent thrombolysis for reperfusion. Coronary artery thrombosis was induced by vessel wall electrolytic injury. Thrombotic occlusion was maintained for 60 or 90 min in 4 different groups: (1) control; (2) Na+/H+ exchange inhibitor, BIIB-722 (3 mg/kg) before occlusion; (3) BIIB-722 (0.75 mg/kg) before reperfusion; (4) ischemic preconditioning (4 x 5 min). Thrombolysis with intracoronary recombinant tissue plasminogen activator produced reperfusion in 6.3 +/- 1.4 min (average for 68 dogs). After restoration of blood flow, vessel patency was maintained for 4 h with the glycoprotein IIb/IIIa receptor antagonist, BIBU 52ZW. BIIB-722, administered before (26.9 +/- 3.6%) or after (22.0 +/- 2.3%) 60-min ischemia or preconditioning (18.4 +/- 2.8%), produced comparable and significant reductions in infarct size (percent of area at risk) compared to controls (47.2 +/- 2.0%). After 90 min of ischemia, BIIB-722 administered before occlusion (37.3 +/- 1.1%) and ischemic preconditioning (35.0 +/- 4.8%) provided significant cardioprotection compared to control (45.9 +/- 1.8%). BIIB-722 was not cardioprotective when administered during occlusion (48.0 +/- 2.4%). The results indicate that Na+/H+ exchange inhibition and preconditioning provide a comparable degree of cardioprotection against 60 min of regional ischemia. However, when the regional ischemic period is extended to 90 min, the degree of cardioprotection is markedly reduced. Further studies incorporating clinically relevant events such as thrombosis and thrombolysis are required before one can conclude that Na+/H+ exchange inhibition is effective against more prolonged myocardial ischemia.
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PMID:Effect of sodium/hydrogen exchange inhibition on myocardial infarct size after coronary artery thrombosis and thrombolysis. 1689 91

Thrombolytic therapy with rtPA increases the risk of hemorrhagic transformation (HT) after cerebral ischemia. We employed contrast enhancement MRI with Gd-DTPA to detect HT in a rat model of embolic stroke treated with rtPA and a glycoprotein IIb/IIIa receptor antagonist, 7E3 F(ab')2, at 4 h after embolic stroke. Male Wistar rats were subjected to embolic stroke and treated with the combination of rtPA and 7E3 F(ab')2 (n=12) or with saline (n=10) at 4 h after onset of stroke. MRI studies were performed immediately and at 24 h after embolization using a 7-T system. Histological measurements were obtained at 48 h. With Gd-DTPA, T1WI images and permeability related MRI parameters (the blood-to-brain transfer constant, Ki, and the distribution volume of mobile protons, Vp) of 15 out of 18 animals showed hyperintensity regions in gross or microscopic HT areas at 24 h, confirmed histologically at 48 h post stroke. Contrast enhancement MRI detected six of seven (86%) animals with gross HT and nine of eleven (82%) animals with microscopic HT at 24 h after ischemia. Two of eighteen animals with HT, had MRI indices of hemorrhage at 3 h post stroke. However, compared to HT data measured histologically at 48 h in embolic stroke rats, the enhanced areas by Gd-DTPA at 24 h were larger, and the patterns (time, intensity and region) did not directly correlate to the subtypes of HT, i.e., gross or microscopic hemorrhage. Contrast enhancement MRI using Gd-DTPA provides a method to detect gross and microscopic HT after stroke in rats.
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PMID:Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat. 1695 Feb 36

Antegrade femoral artery access is commonly used for percutaneous transluminal revascularization of ipsilateral lower limbs in patients with critical limb ischemia. While hemostasis at the end of the procedure can be achieved by manual compression, this may lead to an increase in local vascular complications. Femoral artery closure devices, such as the Angioseal collagen plug and anchor device, have been approved and shown of benefit after retrograde femoral artery catheterization. To date, there are however no data on the use of such arteriotomy closure device after antegrade femoral access. We hereby report a case series of five patients in whom Angioseal was successfully used after antegrade femoral puncture and below-the-knee percutaneous transluminal angioplasty. In all cases the device enabled immediate and complete hemostasis without major complications, despite the intense antithrombotic regimen, including heparin, aspirin, and clopidogrel in all patients, as well as glycoprotein IIb/IIIa inhibitors (in two patients) and fibrinolytic therapy (in one).
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PMID:Angioseal use after antegrade femoral arteriotomy in patients undergoing percutaneous revascularization for critical limb ischemia: a case series. 1705 91

Adverse cardiovascular events are the consequence of a molecular chain reaction at the site of vulnerable plaques. Key players are platelets and coagulation factors that are activated following plaque rupture and often cause arterial obstruction. Thrombin, a plasma serine protease, plays a role in hemostasis of coagulation as well as in thrombosis and cell growth, leading to restenosis and atherosclerosis. Interesting and promising new molecules, the direct thrombin inhibitors, have been shown to be as effective as the combination of glycoprotein IIb-IIIa inhibitors and heparin for the prevention of arterial thrombosis. Until recently, direct thrombin inhibitors could be applied only parenterally; therefore, therapy was limited to hospitalized patients. As a result of recent drug development, orally active direct thrombin inhibitors are now available and have been evaluated for the long-term treatment of venous thrombosis and arterial fibrillation. Due to their specific pharmacodynamic characteristics by binding directly to thrombin--and thus inhibiting platelet aggregation and fibrin generation--these novel drugs may also have therapeutic potential for the treatment of atherothrombotic disease and its complications such as myocardial infarction, stroke or limb ischemia.
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PMID:Therapeutical potential of direct thrombin inhibitors for atherosclerotic vascular disease. 1746 31

Periprocedural myonecrosis, as evidenced by elevated creatine kinase-myocardial bound (CK-MB) levels, occurs in up to 25% of patients undergoing percutaneous coronary intervention (PCI) and has been linked with an increased risk of adverse short- and long-term clinical outcomes. Such myonecrosis arises from three main pathophysiological mechanisms: procedure-related complications, lesion-specific characteristics (e.g., large thrombus burden, plaque volume), and patient-specific characteristics (e.g., genetic predisposition, arterial inflammation). Periprocedural myonecrosis has not been definitively identified as the cause of postprocedural ischemic events, although agents that reduce or prevent thrombosis--including aspirin, thienopyridines, heparin, low-molecular-weight heparins, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors--have been shown to reduce the incidence of ischemic outcomes in this population, as have agents that reduce inflammation (aspirin, statins). At the same time, antithrombotic agents are known to increase the risk of bleeding and the use of transfusions, which have likewise been associated with worse outcomes in these patients. Thus, optimal management of patients undergoing PCI represents a balance between minimizing the risk of ischemic outcomes and simultaneously minimizing the risk of major bleeding. It may be that patients who have only minor, untreated postprocedural elevations in CK-MB level (with no clinical or angiographic signs of ischemia) might have a better prognosis than patients who have normal CK-MB levels but who suffer major bleeding complications.
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PMID:Evolution of anticoagulant and antiplatelet therapy: benefits and risks of contemporary pharmacologic agents and their implications for myonecrosis and bleeding in percutaneous coronary intervention. 1822 47

Platelet hyperaggregability and associated thrombosis have been documented in a number of cardiovascular disease states. While one of the current mainstays of anti-thrombotic treatment (i.e. aspirin, clopidogrel, glycoprotein IIb/IIIa antagonists) has been directed at reducing platelet activation and aggregation, it is apparent that there are limitations to the effectiveness of these therapies. Nitric oxide (NO) plays an important role in platelet physiology. The ability of NO to regulate cyclic guanosine-3,'5'-monophosphate (cGMP), via activation of soluble guanylate cyclase, is the principal mechanism of negative control over platelet activity. NO is not only of the endothelial source, it is also released from activated platelets, providing a negative feedback. Studies in patients with symptomatic ischemia, chronic heart failure, diabetes and various risk factors for cardiovascular disease have demonstrated that platelets from these subjects exhibit reduced responsiveness to the anti-aggregating efficacy of NO: a phenomenon termed "platelet NO resistance". It constitutes an impaired physiological response to endogenous NO (endothelium-derived relaxing factor or EDRF), and as such may contribute to the increased risk of ischemic events. NO resistance also accounts for reduced pharmaco-activity of exogenous NO donors, e.g. organic nitrates. Platelet NO resistance results largely from a combination of "scavenging" of NO by superoxide anion radical and inactivation of soluble guanylate cyclase. NO resistance has both diagnostic and prognostic implications. The current review examines the association of platelet NO resistance with pathological hyperaggregability and discusses potential therapeutic strategies targeting this abnormality.
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PMID:Platelet hyperaggregability: impaired responsiveness to nitric oxide ("platelet NO resistance") as a therapeutic target. 1832 4

Bivalirudin has been associated with decreased bleeding, with similar rates of ischemia in patients with stable angina, unstable angina, non-ST elevation myocardial infarction and elective percutaneous coronary intervention (PCI). The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial tested whether with primary PCI, bivalirudin--compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor--reduced bleeding and net clinical benefit (bleeding, death, reinfarction, target-vessel revascularization for ischemia or stroke). Bivalirudin reduced major bleeding by 40% (4.9 vs 8.3%; risk ratio [RR]: 0.60; 95% confidence interval [CI]: 0.46-0.77; p < 0.0001) as compared with unfractionated heparin and a IIb/IIIa antagonist. Net adverse clinical events were reduced (9.2 vs 12.1%; RR: 0.76: 95% CI: 0.63-0.92; p = 0.005). Cardiac death and total death at 30 days were reduced with bivalirudin (1.8 vs 2.9%; p = 0.03) and (2.1 vs 3.1%; p = 0.047), and at 12 months (2.1 vs 3.8%; p < 0.005) and (3.4 vs 4.8%; p = 0.029), respectively. Bivalirudin reduced bleeding and net adverse clinical events as well as mortality compared with unfractionated heparin and a glycoprotein IIb/IIIa inhibitor. Bivalirudin is an attractive antithrombotic choice in patients undergoing primary PCI.
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PMID:HORIZONS trial: a step forward for primary percutaneous coronary intervention. 1921 Feb 8

Women with non-ST-elevation acute coronary syndrome are at increased risk for ischemic and bleeding complications compared with men. We examined the impact of gender and antithrombotic therapy for non-ST-elevation acute coronary syndrome on outcomes in patients in the ACUITY trial. Patients were randomized to heparin (unfractionated or enoxaparin) plus a glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin plus a GPI, or bivalirudin alone. We compared major bleeding unconnected to coronary artery bypass grafting, composite ischemia (death, myocardial infarction, or revascularization), and net clinical outcome (composite ischemia or bleeding) in (1) men versus women overall and undergoing percutaneous coronary intervention (PCI) and (2) women overall and undergoing PCI by antithrombotic strategy. Of 13,819 patients enrolled, 4,157 were women (30.1%). Women had similar 30-day composite ischemia (7% vs 8%, p = 0.07) but greater 30-day rates of major bleeding (8% vs 3% p <0.0001) and net clinical outcomes (13% vs 10% p <0.0001) than men. One-year composite ischemia and mortality was similar. In women, bivalirudin compared with heparin + GPI resulted in less 30-day major bleeding (5% vs 10%, p <0.0001) but similar composite ischemia (7% vs 6%, p = 0.15). No differences were observed in rates of 1-year composite ischemia or mortality in women who received bivalirudin versus heparin + GPI. Results were similar in women undergoing PCI. In conclusion, women had similar 30-day mortality and composite ischemia but higher net clinical adverse events due to more bleeding complications than men; 1-year mortality was similar for men and women. In women, bivalirudin monotherapy compared with a GPI-based strategy resulted in significantly decreased bleeding but similar rates of 1-year composite ischemia and mortality.
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PMID:Impact of gender and antithrombin strategy on early and late clinical outcomes in patients with non-ST-elevation acute coronary syndromes (from the ACUITY trial). 1940 58

Acute limb ischemia is still the most frequent cause of major limb loss. Timely and fast revascularization is the key for limb salvage and patient survival. Large randomized trials showed equivalency of surgical and endovascular revascularization by means of local lysis with urokinase (TOPAS, STILE). New lytic agents and their modified application such as via a pulse spray catheter or combined with an ultrasound catheter and the combination with glycoprotein IIb/IIIa receptor antagonists have increased the efficacy and speed of thrombolysis. Recently, mechanical thrombectomy devices have become more widespread because intervention time and bleeding complications can be reduced. This review article summarizes the clinical presentation of and the treatment options for acute arterial occlusive disease caused either by embolism or local thrombosis.
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PMID:Treatment of acute limb ischemia with focus on endovascular techniques. 1958

Abciximab and eptifibatide have been shown to reduce ischemic complications compared with heparin alone in patients with acute coronary syndromes who undergo percutaneous coronary intervention. Whether 1 agent is safer and/or more effective has not been prospectively examined. The aim of this study was to assess the outcomes related to downstream glycoprotein IIb/IIIa inhibitor treatment selection during percutaneous coronary intervention in 2,211 patients with moderate and high-risk acute coronary syndromes in the prospective multicenter Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. The protocol permitted operator selection of abciximab (n = 835) or eptifibatide (n = 1,376) for routine use in the trial. Multivariate and propensity-based adjustments were used to assess the independent association of glycoprotein IIb/IIIa inhibitor treatment selection with prespecified study end points. Compared to patients receiving eptifibatide, those administered abciximab were older, more likely to be enrolled outside of North America, more frequently had biomarker elevations and ST-segment deviation, but had fewer baseline cardiac risk factors and previous revascularization procedures. After multivariate propensity-based adjustment, abciximab was independently associated with significantly fewer net clinical adverse events (odds ratio 0.61, 95% confidence interval 0.42 to 0.90, p = 0.01), mediated by composite ischemia (odds ratio 0.61, 95% confidence interval 0.38 to 0.98, p = 0.04) and major bleeding (odds ratio 0.58, 95% confidence interval 0.34 to 1.00, p = 0.051). In conclusion, in this prespecified but nonrandomized comparison in patients with acute coronary syndromes who underwent percutaneous coronary intervention with catheterization laboratory initiation of glycoprotein IIb/IIIa inhibitors, the use of abciximab rather than eptifibatide was associated with improved clinical outcomes at 30 days. These findings should be viewed as exploratory in light of the nonrandomized and heterogeneous nature of the comparator groups and significant potential for residual confounding.
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PMID:Comparison of catheterization laboratory initiated abciximab and eptifibatide during percutaneous coronary intervention in acute coronary syndromes (an ACUITY substudy). 2059


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