Heparin protects against skin flap necrosis: relationship to neutrophil recruitment and anti-coagulant activity

Abstract

Heparin has been shown to improve survival of surgical skin flaps. However, it is not known whether the protective effect of heparin is related to its anticoagulative or anti-inflammatory effects. Surgical flaps were raised in the dorsal skin of Sprague-Dawley rats. Neutrophil recruitment was determined by measuring the tissue content of myeloperoxidase (MPO) and clotting time was estimated by assessment of activated partial thromboplastin time (APTT) in plasma. Administration of heparin (150 U/kg) significantly increased skin flap survival from 44% in vehicle-treated controls to 91%. This heparin treatment increased APTT by 4.5 fold. However, administration of 150 U/kg of heparin had no effect on skin flap neutrophil recruitment. In contrast, we found that the polysaccharide fucoidan reduced MPO and also improved skin flap survival. In conclusion, we demonstrate that protective effect of clinically relevant doses of heparin correlates with its ability to prolong clotting time and not to inhibition of neutrophil accumulation in the healing of skin flaps.