title: A novel hollow and perforated flexible wire allows the safe and effective local application of thrombolytic therapy in a mouse model of deep vein thrombosis.
abstract: We tested the feasibility of local thrombolytic therapy via a novel hollow flexible and perforated wire in a mouse model of deep vein thrombosis. Inferior vena cava (IVC) thrombosis was induced by vessel wall exposure to ferric chloride after laparotomy in anesthetized C57Bl/6 mice. Thrombus formation was visualized by intravital microscopy of rhodamine-labeled platelets and leukocytes. A nitinol hypotube coronary wire with perforated tip was inserted via a 0.8 × 40 mm canula into the IVC lumen distal to the site of ferric chloride exposure. Either tissue plasminogen activator (tPA, alteplase) or saline (control) was administered via the platinum wire distal to the thrombus, avoiding mechanical fragmentation. Thrombus size was assessed by immunohistochemistry (platelet CD41 staining). Intravital microscopy of the IVC demonstrated platelet-containing thrombus growth starting 1 min after ferric chloride exposure. Alteplase administration resulted in significant thrombus size reduction within 10-20 min observed by intravital microscopy and confirmed by histological assessment of IVC cross-sections. Saline-treated mice (n = 4) demonstrated near total IVC occlusion with thrombotic material (84 ± 8% of cross-sectional area in serial sections), whereas alteplase-treated mice showed a dose-dependent decrease of thrombotic area [56 ± 5% with 1.5, 39 ± 4 % with 15 and 21 ± 6% with 150 mg/kg, respectively (n = 4)]. We demonstrate that a flexible hollow and perforated wire enables the successful application of thrombolytic therapy to IVC thrombi in mice without vessel wall perforation. Flexible wire-based thrombolytic therapy appears to be a safe and reliable method for thrombus dissolution even in fragile small veins and may become a promising strategy for targeted therapy of small vessel thrombosis.
authors.affiliation: Department of Cardiology and Angiology I, Heart Center Freiburg University, Hugstetter Str. 55, 79106, Freiburg, Germany, thilo.witsch@universitaets-herzzentrum.de.
authors.forename: Thilo
authors.initials: T
authors.lastname: Witsch
authors.forename: Maximilian
authors.initials: M
authors.lastname: Mauler
authors.forename: Nadine
authors.initials: N
authors.lastname: Herr
authors.forename: Daniela
authors.initials: D
authors.lastname: Stallmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Christoph
authors.initials: C
authors.lastname: Hehrlein
authors.forename: Daniel
authors.initials: D
authors.lastname: Duerschmied
mesh_terms: D000497:Alloys; D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D008297:Male; D061185:Mechanical Thrombolysis / Q000295:instrumentation / Q000379:methods; D051379:Mice; D015912:Thrombolytic Therapy / Q000295:instrumentation / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D020246:Venous Thrombosis / Q000139:chemically induced / Q000628:therapy*
chemical_list: D000497:Alloys; D005343:Fibrinolytic Agents; C013616:nitinol; D010959:Tissue Plasminogen Activator