Electric injury model of murine arterial thrombosis

Murine models of arterial thrombosis have gained utility with applications in genetically manipulated mice. Implementation of current models requires specialized equipment and provides limited outcome measures. A new murine model of continuously monitored arterial thrombosis was created.

An electric injury was delivered to the exterior surface of the common carotid artery using the flat end of a 140-mum steel microsurgery needle connected to the anode of a 3-V battery source. Direct current was delivered for 30 s. The developing thrombus was apparent as a white, platelet-dominated region at the site of injury. This region was continuously monitored and recorded by videotape for 30 min. Subsequently, the thrombus area was measured directly on the TV monitor, generating a time course for thrombogenesis. In a further evaluation of the model, three pharmacologically treated groups of mice were evaluated, with drug infusion immediately before thrombus induction: (1) saline (control), (2) heparin (60 units/kg), and (3) GR144053, a GPIIb/IIIa-specific antagonist (10 mg/kg).

The basic model showed consistent thrombus development by 7-9 min, occasionally forming an occlusive thrombus. Most of the thrombi underwent one or more cycles of embolization and thrombus regrowth. In the experimental series, the heparin-treated group had a significantly decreased thrombus area versus controls (p<0.0001); the GR144053-treated mice had no apparent thrombus, supporting a dominant role of platelet aggregation in arterial thrombogenesis.

This new model is simple to do, uses readily available instrumentation, and provides a continuously recorded quantifiable measure of thrombogenesis.