In vivo monitoring of venous thrombosis in mice.
BACKGROUND
Venous thrombosis (VT) is an important cause of morbidity and mortality in clinical medicine. Animal models studying venous thrombosis are scarce and, in most cases, very crude and rely on sacrificing the animals to excise formed thrombi. Developing an in vivo murine model of venous thrombosis can be a powerful tool for studying venous thrombosis.


OBJECTIVE
We sought to use a high-frequency ultrasound system (HFUS) to dynamically and non-invasively monitor thrombus formation in the inferior vena cava (IVC) of mice.


METHODS
We developed a murine model of venous thrombosis using, for detection, the Vevo 770(®), a micro-imaging HFUS. Two different thrombosis models were used to generate thrombi in the IVC of C57Bl/6NCr mice: (i) ligation and (ii) application of ferric chloride (FeCl(3)). We then assessed venous thrombosis by HFUS.


RESULTS
In both models, measurements of the clot pathologically correlated favorably with measurements acquired with HFUS. Thrombus develops less than an hour after ligation or FeCl(3) -induced injury of the IVC and the size of the clot increases over time for up to 24 h. Importantly, we demonstrate that HFUS can be used to monitor the effect of an anticoagulant such as dalteparin until complete resolution of the thrombus.


CONCLUSIONS
These data show that HFUS assesses venous thrombosis in mice reliably and non-invasively. Developing a murine model of thrombosis using more accurate, and clinically more relevant, techniques such as ultrasonography, is a step towards a better understanding of the pathophysiology of venous thromboembolism.
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec, Canada.
M N
MN
Aghourian
C A
CA
Lemarié
M D
MD
Blostein
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002712:Chlorides; D017985:Dalteparin / Q000494:pharmacology; D004195:Disease Models, Animal; D005290:Ferric Compounds; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008991:Monitoring, Physiologic / Q000379:methods*; D013997:Time Factors; D018615:Ultrasonography, Doppler, Color; D018617:Ultrasonography, Doppler, Pulsed; D014682:Vena Cava, Inferior / Q000000981:diagnostic imaging* / Q000601:surgery; D020246:Venous Thrombosis / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000209:etiology
D000925:Anticoagulants; D002712:Chlorides; D005290:Ferric Compounds; D017985:Dalteparin; C024555:ferric chloride