Murine arterial thrombus induction mechanism influences subsequent thrombodynamics

Thromb Res. 2015 May;135(5):939-43. doi: 10.1016/j.thromres.2015.02.016. Epub 2015 Feb 25.

Abstract

Background: The mechanism of thrombotic induction in experimental models can vary greatly, as can the applied evaluative measures, making comparisons among models difficult.

Objectives: This study comparatively evaluated the arterial thrombodynamic response among injury mechanisms.

Methods: Thrombotic responses were induced in mouse carotid arteries, with subsequent intravital imaging using rhodamine-6G-labeled platelets to quantitate platelet accumulation over 30minutes. Nine induction methods were evaluated: brief pinch, temporary hard ligation, cautery/heat, needle puncture, intralumenal wire (scratch), intralumenal adventitia/collagen (2 different models), and brief exposures to either iron-based surface electrolytic injury or ferric chloride.

Results: The accumulation of platelets was variable among induction methods, with a greater response to more severe injury mechanisms, free radical injury, and exposed collagen. Temporal profiles were generated by normalizing data to peak platelet accumulation for each run; rapid platelet development and subsequent detachment were found for mechanical injuries that maintained vessel integrity (pinch and ligation injuries), with more sustained growth for more severe mechanical (wire) injury or breach of the vessel (needle puncture or intralumenal collagen). A delayed but extended temporal response was seen with free radical injury (both electrolytic and ferric chloride).

Conclusions: These findings demonstrate a dependence of platelet thrombodynamics on the method of induction, with collagen exposure causing greater, more prolonged activity, while free-radical injury effected a delayed but sustained platelet thrombus formation with slower resolution. A better understanding of how these various injury models relate to clinical causes of arterial thrombosis is needed for optimal translational interpretation of murine models of thrombosis.

Keywords: Arteries; Fluorescence imaging; Platelets; Thrombosis; Vascular injuries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / pathology*
  • Carotid Arteries / pathology*
  • Carotid Artery Thrombosis / etiology*
  • Carotid Artery Thrombosis / pathology*
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Optical Imaging