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Thromb Haemost 2006; 96(01): 68-72
DOI: 10.1160/TH06-02-0103
Animal Models
Schattauer GmbH

Early in vivo anticoagulation inhibits the angiogenic response following hindlimb ischemia in a rodent model

Erich V. De Paula
1   Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
,
Mariane C. F. Nascimento
1   Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
,
Celso D. Ramos
2   State University of Campinas School of Medicine, Campinas, SP, Brazil
,
Margareth C. Ozelo
1   Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
,
Tânia F. Machado
1   Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
,
Ana T. Guillaumon
2   State University of Campinas School of Medicine, Campinas, SP, Brazil
,
Valder R. Arruda
3   Department of Pediatrics, University of Pennsylvania School of Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
,
Joyce M. Annichino-Bizzacchi
1   Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
2   State University of Campinas School of Medicine, Campinas, SP, Brazil
› Author AffiliationsFinancial support: This work was supported by grants from FAPESP to JMAB.
Further Information

Publication History

Received 20 February 2006

Accepted after resubmission 24 May 2006

Publication Date:
29 November 2017 (online)

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Summary

Emerging findings have demonstrated the critical role of blood clotting factors in the formation and stabilization of embryonic blood vessels. Whether a similar role is true during post-natal angiogenesis remains to be determined. Here we sought to determine whether the suppression of thrombin generation with anticoagulant drugs at doses routinely used for therapeutic purposes would affect the angiogenesis pattern following hindlimb ischemia in rats. Animals were treated with r- hirudin or enoxaparin within six hours post induction of hindlimb ischemia, whereas two other groups received oral anticoagulation warfarin beginning at day 3 post-ischemia or saline (as control). The revascularization anatomical and functional responses were evaluated 30 days following tissue ischemia. Chronic administration of the drugs resulted in stable anticoagulation in all animals throughout the experiment. Animals that received drugs with fast anticoagulation effects (i.e. r-hirudin and enoxaparin) presented a significant decrease in capillary density and capillary-to-myocyte ratio compared to control animals. These effects were not associated with changes in relative perfusion of the hindlimb at steady state. These anti-angiogenic effects occur in a time-dependent manner, since delayed inhibition of coagulation (> 72 hours) presents no adverse effect on the angiogenic response. We conclude that the use of anticoagulant drugs immediately after tissue ischemia induction hampers in vivo angiogenic response in a rodent hindlimb ischemia model.

Keywords

Angiogenesis - warfarin - hirudin - heparin - anticoagulant
 

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