title: Visualization of in vivo thromboprophylactic and thrombolytic efficacy of enoxaparin in laser-induced vascular endothelial injury model using multiphoton microscopy.
abstract: Enoxaparin is used postoperatively for the prevention of venous thromboembolism. In vitro studies and clinical trials have demonstrated the anticoagulant and antithrombotic efficacy of enoxaparin. In this study, we visualised thromboprophylactic and thrombolytic efficacy of enoxaparin in a laser-induced thrombus formation model in vivo using two-photon laser-scanning microscopy (TPLSM). Thrombus was induced by the selective irradiation of vascular endothelium in arterioles of the cecum of green fluorescent protein transgenic mice. The thromboprophylactic and thrombolytic efficacy of enoxaparin was visualised in vivo real-time using TPLSM. Platelet adhesion, aggregation, and platelet-dependent thrombus formation were observed in the laser-induced thrombus formation model with reproducibility. Laser-induced thrombus formation was significantly inhibited by enoxaparin pretreatment as the thromboprophylactic agent, as compared with control. The mean thrombus volumes were 652 microcubic meters in mice pretreated with enoxaparin and 8906 microcubic meter in control mice. Enoxaparin reduced the volume of laser-induced thrombus when using it as a thrombolytic agent. The mean rate of reduction was 59 percent. In a lipopolysaccharide-induced sepsis model, thromboprophylactic efficacy of enoxaparin was also observed in vivo in real-time. In vivo thromboprophylactic and thrombolytic efficacy of enoxaparin can be visualised at the single platelet level in the laser-induced endothelium injury model using TPLSM.
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Koike
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Okigami
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Araki
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.affiliation: Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.affiliation: Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
keywords: Enoxaparin; intravital imaging; multiphoton microscopy; thrombus formation