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

Erich V. De Paula; Mariane C. F. Nascimento; Celso D. Ramos; Margareth C. Ozelo; Tânia F. Machado; Ana T. Guillaumon; Valder R. Arruda; Joyce M. Annichino-Bizzacchi

doi:10.1160/TH06-02-0103

Thrombosis and Haemostasis, Table of Contents

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

Authors

Erich V. De Paula

¹Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
Mariane C. F. Nascimento

¹Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
Celso D. Ramos

²State University of Campinas School of Medicine, Campinas, SP, Brazil
Margareth C. Ozelo

¹Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
Tânia F. Machado

¹Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
Ana T. Guillaumon

²State University of Campinas School of Medicine, Campinas, SP, Brazil
Valder R. Arruda

³Department of Pediatrics, University of Pennsylvania School of Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Joyce M. Annichino-Bizzacchi

¹Hematology and Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil

²State University of Campinas School of Medicine, Campinas, SP, Brazil

Abstract

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

Full Text

References

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