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Ulrich Martin - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of thrombolytic and systemic effects of the novel Recombinant Plasminogen Activator BM 06.022 compared with alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis
Journal of the American College of Cardiology, 1992Co-Authors: Ulrich MartinAbstract:The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue Plasminogen Activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Costas T Lambrew - One of the best experts on this subject based on the ideXlab platform.
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hemorrhagic events during therapy with Recombinant tissue type Plasminogen Activator heparin and aspirin for acute myocardial infarction
Annals of Internal Medicine, 2020Co-Authors: Edwin G Bovill, Desire Collen, Michael L Terrin, David C Stump, Andrew D Berke, Margaret Frederick, Frederick Feit, Joel M Gore, David L Hillis, Costas T LambrewAbstract:▪ Objectives: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of Recombinant Plasminogen Activator (rt-PA) on hemo...
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hemorrhagic events during therapy with Recombinant tissue type Plasminogen Activator heparin and aspirin for acute myocardial infarction results of the thrombolysis in myocardial infarction timi phase ii trial
Annals of Internal Medicine, 1991Co-Authors: Edwin G Bovill, Desire Collen, Michael L Terrin, David C Stump, Andrew D Berke, Margaret Frederick, Frederick Feit, Joel M Gore, David L Hillis, Costas T LambrewAbstract:Objectives To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of Recombinant Plasminogen Activator (rt-PA) on hemorrhagic events. Design A multicenter, randomized, controlled trial. Setting Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). Interventions Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. Measurements Patients were monitored for hemorrhagic events during hospitalization. Main results In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. Conclusions Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy.
Allen Seals - One of the best experts on this subject based on the ideXlab platform.
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randomized comparison of coronary thrombolysis achieved with double bolus reteplase Recombinant Plasminogen Activator and front loaded accelerated alteplase Recombinant tissue Plasminogen Activator in patients with acute myocardial infarction
Circulation, 1996Co-Authors: Christoph Bode, Richard W Smalling, Robert L Feldman, Gunther Berg, Curtis Burnett, Gerald Lorch, John M Kalbfleisch, Robert Chernoff, Leonard G Christie, Allen SealsAbstract:Background The therapeutic benefit of thrombolytic therapy has been shown to correlate directly with completeness (TIMI grade 3 flow) and speed of reperfusion of the infarct-related coronary artery. The purpose of the RAPID II study was to determine whether a double-bolus regimen of reteplase, a recently developed deletion mutant of wild-type tissue Plasminogen Activator, could improve 90-minute coronary artery patency rates achieved with the most successful standard regimen, an “accelerated” front-loaded infusion of alteplase. Methods and Results Three hundred twenty-four patients with acute myocardial infarction were randomized to receive (along with intravenous heparin and aspirin) either a 10 plus 10 megaunits double bolus of reteplase or front-loaded alteplase. The primary end point of “patency at 90 minutes, graded according to the TIMI classification” was centrally assessed in a blinded fashion. Infarct-related coronary artery patency (TIMI grade 2 or 3) and complete patency (TIMI grade 3) at 90 mi...
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more rapid complete and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction
Circulation, 1995Co-Authors: Richard W Smalling, Christoph Bode, John Kalbfleisch, Semi Sen, Peter Limbourg, Florian Forycki, Gabriel B Habib, Robert L Feldman, S H Hohnloser, Allen SealsAbstract:Background Early restoration and maintenance of normal (TIMI 3) blood flow during acute myocardial infarction is critical for optimal preservation of left ventricular function and survival. Recombinant Plasminogen Activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type Plasminogen Activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other Plasminogen Activators in animal models. Methods and Results The RAPID Trial was designed to test the hypothesis that bolus administration of one or more dosage regimens of r-PA was superior to standard-dose alteplase (TPA) in achieving infarct-related artery patency 90 minutes after initiation of treatment. Six hundred six patients with acute myocardial infarction were randomized to one of four treatment arms: (1) TPA 100 mg IV over 3 hours, (2) r-PA as a 15-MU single bolus, (3) r-PA as a 10-MU bolus followed by 5 MU 30 minutes later, or (4) r-PA as a 10-MU bolus followed by 10 MU 30 minutes ...
Maria Mercedes Binda - One of the best experts on this subject based on the ideXlab platform.
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prevention of adhesion formation in a laparoscopic mouse model should combine local treatment with peritoneal cavity conditioning
Human Reproduction, 2009Co-Authors: Maria Mercedes Binda, Philippe R KoninckxAbstract:background: Adhesion formation results from a series of local events at the trauma site. This process can be enhanced by factors derived from the peritoneal cavity such as mesothelial cell hypoxia (pneumoperitoneum with pure CO2), reactive oxygen species (pneumoperitoneum with more than 4% oxygen), desiccation and mesothelial trauma produced through manipulation. Adhesion prevention, therefore, should combine local treatment while minimizing adverse peritoneal factors through conditioning of the pneumoperitoneum. methods: In a laparoscopic mouse model, adhesion induction comprised a mechanical lesion together with a humidified pneumoperitoneum for 60 min with pure CO2 at 378C. Adhesion prevention consisted of a combination of treatments known to reduce adhesions, i.e. pneumoperitoneum with CO2 with the addition of 3–4% O2, reduction of body temperature (BT) to 328C and application of antiadhesion products such as anti-inflammatory drugs (dexamethasone, nimesulide), calcium-channel blockers (diltiem), surfactants (phospholipids), barriers (Hyalobarrier gel), reactive oxygen species scavengers (superoxide dismutase and ascorbic acid) and Recombinant Plasminogen Activator. results: The addition of 3% O2 to the pneumoperitoneum or a lower BT decreased adhesions by 32% or 48%, respectively (P , 0.05, Wilcoxon), but were without additional effects when combined. In addition, if dexamethasone or Hyalobarrier w gel were administrated, the total reduction was 76% (P ¼ 0.04) or 85% (P , 0.02), respectively. conclusions: Combining pneumoperitoneum conditioning together with dexamethasone or a barrier resulted in significant adhesion reduction in a laparoscopic mouse model.
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effect of reteplase and pai 1 antibodies on postoperative adhesion formation in a laparoscopic mouse model
Surgical Endoscopy and Other Interventional Techniques, 2009Co-Authors: Maria Mercedes Binda, Paul Declerck, Bart W J Hellebrekers, Philippe KoninckxAbstract:Background Postoperative adhesions remain an important clinical problem, accounting for infertility, chronic pain and bowel obstruction. Its prevention is still inadequate and overall poorly understood. The aim of this study was to investigate the effect of Reteplase (a Recombinant Plasminogen Activator, r-PA) and of PAI-1 antibodies upon adhesion formation in a laparoscopic model.
Edwin G Bovill - One of the best experts on this subject based on the ideXlab platform.
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hemorrhagic events during therapy with Recombinant tissue type Plasminogen Activator heparin and aspirin for acute myocardial infarction
Annals of Internal Medicine, 2020Co-Authors: Edwin G Bovill, Desire Collen, Michael L Terrin, David C Stump, Andrew D Berke, Margaret Frederick, Frederick Feit, Joel M Gore, David L Hillis, Costas T LambrewAbstract:▪ Objectives: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of Recombinant Plasminogen Activator (rt-PA) on hemo...
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hemorrhagic events during therapy with Recombinant tissue type Plasminogen Activator heparin and aspirin for acute myocardial infarction results of the thrombolysis in myocardial infarction timi phase ii trial
Annals of Internal Medicine, 1991Co-Authors: Edwin G Bovill, Desire Collen, Michael L Terrin, David C Stump, Andrew D Berke, Margaret Frederick, Frederick Feit, Joel M Gore, David L Hillis, Costas T LambrewAbstract:Objectives To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of Recombinant Plasminogen Activator (rt-PA) on hemorrhagic events. Design A multicenter, randomized, controlled trial. Setting Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). Interventions Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. Measurements Patients were monitored for hemorrhagic events during hospitalization. Main results In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. Conclusions Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy.