The effect of recombinant hirudin on rabbit ear flaps with venous insufficiency

The effect of recombinant hirudin, which is the most powerful antithrombotic agent, on flaps with venous insufficiency was investigated. Oedema and congestion are frequent on flaps, causing necrosis unpredictably. Venous insufficiency and thrombosis are experimentally and clinically more frequent than arterial occlusion. Twenty-one adult New Zealand rabbits were used in this study. Skin flaps (3 × 6 cm) were elevated on a 1-cm-wide pedicle on rabbit ears. The artery, nerve, and vein were exposed and examined with the aid of a surgical microscope. Venous insufficiency was established by cutting the vein and nerve. In the control group, no additional surgical or medical procedures were performed and the ear flap was inset to its original location. Subcutaneous low molecular weight heparin (LMWH; 320 IU/kg) was administered to a second group of rabbits after the same surgery, and recombinant hirudin (2 μg) was administered via the pedicle artery 5 minutes after the vein and nerve were bound and cut in a third group of rabbits. Compared with control and LMWH groups on day 3 and 7, the hirudin-treated group had less hair loss, lower oedema scores and less haematoma formation. Furthermore, a lower size of necrotic areas and an increase in the circulating area on day 7 was found in the hirudin-treated group. In addition, angiography revealed new vessel development (neovascularisation) only in the hirudin group. On histologic sections, hirudin-treated animals had lower oedema, inflammation and congestion scores than animals in the other two groups. Thus, when administered into the ear flap through the pedicle as a pure recombinant preparation, hirudin increased flap survival by its antithrombotic effects and by accelerating neoangiogenesis. Recombinant hirudin may be used in clinical practice to treat flaps with venous problems and to increase survival rates.