Effect of mutalysin II on vascular recanalization after thrombosis induction in the ear of the hairless mice model

Abstract

Mutalysin II (mut-II) is an α-fibrinogenase isolated from Lachesis muta muta (bushmaster) snake venom. The enzyme lyses fibrin clots in vitro, and this activity does not depend on plasminogen activation.The aim of this study was to assess by intravital microscopy the effect of Mutalysin II on the recanalization of microvessels after thrombus induction in the ears of hairless mice. Photochemical thrombus formation was induced after i.v. injection of 5% fluorescein isothiocyanate labelled dextran (FITC-dextran) followed by mercury light exposure of individual microvessels of the ear of five anesthetized animals. Video playback analysis of intravital microscopy images of the ear microcirculation permitted us to measure blood flow velocity (μm/s) under control conditions (before thrombus formation) in the ear microvessels. Thirty minutes after thrombus formation (blood flow velocity stopped completely), each animal ( n=5) was infused with Mutalysin II (2.0 mg/kg, i.v.). All animals treated with Mutalysin II showed evident thrombolysis after approximately 12 min, followed by recanalization. A separate group of mice ( n=5) which received urokinase type-plasminogen activator (u-PA, 250 U/mouse, i.v.) showed blood flow restoration within the same interval (12 min). These in vivo data suggest that Mutalysin II has the potential to be an effective thrombolytic agent.