DIPHENYLHYDANTOIN SODIUM PROMOTES EARLY AND MARKED ANGIOGENESIS AND RESULTS IN INCREASED COLLAGEN DEPOSITION AND TENSILE-STRENGTH IN HEALING WOUNDS

Background. Sodium diphenylhydantoin (DpH) (phenytoin) was first intro duced as an antiepileptic in 1938. One of its side effects, gingival h yperplasia, prompted investigation into the possible application of th is drug as a promoter of wound healing. Since the late 1950s phenytoin has been used in a variety of clinical situations. However its exact mechanism of action is still debated. The aim of this study was to det ermine the effect of DpH on wound healing in an incisional rat model. Methods. A four dorsal wound model was used, and each cephalad wound h ad a polyvinyl alcohol sponge placed in a subcutaneous pocket just abo ve its cephalad end. Caudal and cephalad wounds were treated with 10 m g DpH in 200 mu l carrier, and the other two wounds received an equal volume of the saline vehicle as controls on the day of wounding and on the third and sixth postoperative days. The animals were killed on th e tenth postwounding day. Tensile strength of flesh and fixed scars wa s determined losing constant speed tensiometry, and wound hydroxyproli ne was determined spectophotometrically. Results. There was a highly s ignificant increase in both flesh and fixed wound tensile strength of all DpH-treated wounds compared with controls (p < 0.001). This was re flected by a significant increase in polyvinyl alcohol sponge hydroxyp roline in DpH-treated wounds compared with saline-treated wounds (p = 0.002). Histologic examination of these wounds was performed at 3 and 6 days after wounding: There was moderate fibroblast infiltration with a marked inflammatory infiltrate and neovascularization in the DPH-tr eated wounds compared with controls at 3 days. By day 6, the inflammat ory infiltrate had almost totally receded in the treated wounds, but f ibroblast infiltration and angiogenesis were still persistently marked . In comparison the saline-treated wounds still had moderate inflammat ory and fibroblast infiltrate and mild angiogenesis. Conclusions. DPH alters the natural course of wound healing and may be of benefit in cl inical situations where defective wound collagen deposition may lead t o poor wound healing and consequent morbidity and mortality.