hirudin and Graft-Occlusion--Vascular

In the HORIZONS-AMI trial, bivalirudin compared to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) improved net clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) at the cost of an increased rate of acute stent thrombosis. We sought to examine whether these effects are dependent on time to treatment.. The interaction between anticoagulation regimen and symptom onset to first balloon inflation time (SBT) on the 30-day and three-year rates of major adverse cardiac events (MACE) was examined in 3,199 randomised patients according to SBT ≤3 hours versus >3 hours. Among patients with an SBT ≤3 hours, bivalirudin resulted in higher 30-day rates of MACE compared to UFH plus a GPI. Non-significant differences were observed in patients with an SBT >3 hours. Similar results were found for MACE at three years and stent thrombosis and reinfarction at 30 days and three years. By multivariable analysis, bivalirudin was an independent predictor of MACE at 30 days and three years in patients with an SBT ≤3 hours, but not in patients with SBT >3 hours.. Bivalirudin compared to UFH plus a GPI is associated with an increased rate of stent thrombosis and MACE in patients with short SBTs, but not in those with longer SBTs.

Topics: Aged; Anticoagulants; Antithrombins; Cause of Death; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Heparin; Hirudins; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Complications; Recombinant Proteins; Recurrence; ST Elevation Myocardial Infarction; Stroke; Thrombosis; Time-to-Treatment; Treatment Outcome

Topics: Acute Coronary Syndrome; Aged, 80 and over; Antithrombins; Combined Modality Therapy; Coronary Angiography; Coronary Artery Bypass; Echocardiography; Embolic Protection Devices; Graft Occlusion, Vascular; Hirudins; Humans; Male; Peptide Fragments; Recombinant Proteins; Saphenous Vein; Thrombectomy; Venous Thrombosis

To develop small-diameter vascular grafts with a microstructure similar to native matrix fibers and with chemically modified microfibers to prevent thrombosis.. Microfibrous vascular grafts (1-mm internal diameter) were fabricated by electrospinning, and hirudin was conjugated to the poly (L-lactic acid) microfibers through an intermediate linker of poly(ethylene glycol). The modified microfibrous vascular grafts were able to reduce platelet adhesion/aggregation onto microfibrous scaffolds, and immobilized hirudin suppressed thrombin activity that may interact with the scaffolds. This 2-pronged approach to modify microfibrous vascular graft showed significantly improved patency (from 50% to 83%) and facilitated endothelialization, and the microfibrous structure of the vascular grafts allowed efficient graft remodeling and integration, with the improvement of mechanical property (elastic modulus) from 3.5 to 11.1 MPa after 6 months of implantation.. Microfibrous vascular grafts with antithrombogenic microfibers can be used as small-diameter grafts, with excellent patency and remodeling capability.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Coated Materials, Biocompatible; Elastic Modulus; Endothelial Cells; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Hirudins; Humans; Lactic Acid; Materials Testing; Platelet Adhesiveness; Platelet Aggregation; Polyesters; Polyethylene Glycols; Polymers; Prosthesis Design; Rats; Rats, Sprague-Dawley; Thrombin; Thrombosis; Time Factors; Vascular Patency

Topics: Anticoagulants; Arterial Occlusive Diseases; Aspirin; Clopidogrel; Drug Resistance; Drug Therapy, Combination; Factitious Disorders; Female; Graft Occlusion, Vascular; Heparin, Low-Molecular-Weight; Hirudins; Humans; Iliac Artery; Middle Aged; Munchausen Syndrome; Phenprocoumon; Platelet Aggregation Inhibitors; Recombinant Proteins; Recurrence; Reoperation; Ticlopidine; Treatment Refusal; Vascular Surgical Procedures

Microvascular surgical techniques now play an extremely important role in reconstructive surgery. Failures still persist and are most commonly due to thrombotic occlusion of the microvascular anastomosis. Five to 20% of all free tissue transfers and replants are affected. A logical step in the effort to resolve this problem would be the infusion of the newly available recombinant hirudin (r-hirudin). The value of r-hirudin in microvascular surgery has not been investigated. An animal model mimicking the thrombotic mechanisms similar to those in the clinical situation has been described in which a length of rabbit femoral artery is excised, turned inside out and reinserted into the vessel with two standard microvascular anastomoses. The major factors in clinical anastomosis failure are represented in this animal model by medial disruption, imperfect vessel wall alignment, needle holes, trauma, foreign suture material and changes in flow. The type III adventitial collagen turned inward reproduces the clinical problem of adventitial strands becoming caught in the anastomosis. A predictable rate of thrombosis results depending on inversion graft length: a 2 mm segment has an occlusion rate at one week of about 30%. Using this model heparin infusions significantly decrease thrombosis rates compared to saline. Using an almost identical model we have begun a study the effect of r-hirudin on microvascular patency. New Zealand White male rabbits were anaesthetized with ketamine and xylazine. Through a groin incision the femoral vein was catheterized and tubing connected to an infusion pump. The femoral artery was exposed, and the adventitia aggressively removed since it is difficult to minimally debride adventitia in a reproducible fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anastomosis, Surgical; Animals; Femoral Artery; Fibrinolytic Agents; Graft Occlusion, Vascular; Heparin; Hirudin Therapy; Hirudins; Male; Microsurgery; Rabbits; Recombinant Proteins; Vascular Patency