Abstract
Phenytoin has previously been shown to accelerate wound healing through upregulation of angiogenesis and promotion of collagen deposition. These reported effects led us to hypothesise that phenytoin could be used locally at the tendon repair site to increase the rate and strength of healing. Systemic treatment with phenytoin has also been shown to increase the thickness and density of calvarial and maxillary bones in humans, and promote fracture healing in rabbits, rats and mice. Based on these and similar studies we hypothesised that local percutaneous injection of phenytoin solution into a fracture site would result in improved fracture healing without the risk of the side effects of systemic administration of the drug.
Methods: For the tendon repair study, a previously validated rabbit tendo-achilles tenotomy model was chosen. Animals underwent a transverse tenotomy of the FDL and TA tendons. These were immediately repaired using 3/0 ethibond sutures using the modified Kessler technique, prior to local application of either a phenytoin or buffer gel formulation. At 21 days post-op, the animals were euthanased and the TA harvested for tensiometry testing and collagen content estimation, and the FDL was harvested for histological analysis.
For the fracture study, a rat femur fracture model was utilised. Adult male Sprague-Dawley rats were anaesthetised. Following a medial parapatellar approach, the femur was cannulated using an 18 gauge cannula. The cannula was cut flush with the distal femur and countersunk. The skin and retinaculum were closed with 5.0 monocryl. The nailed femur was then fractured using a 3 point bending technique. The femurs were xrayed to ensure each fracture was mid-diaphyseal and transverse. At 6 hours post op animals underwent either 1) Fracture site percutaneous injection with 100 μmol phenytoin solution 2) Fracture site percutaneous injection with phosphate buffer solution (PBS) 3) No percutaneous injection. This procedure was once again repeated at 72 hours. At 2 and 4 weeks post op 6 animals from each group were euthanased, their femurs were harvested for biomechanical analysis of stiffness and strength.
Results: There was no difference in tendon diameter, gross adhesion formation, ultimate tensile strength or collagen content between the groups. Histologically, however, there were a significantly greater number of inflammatory cells (p< 0.05) and blood vessels (p< 0.05) in the phenytoin treated tendons compared to controls.
At both 2 and 4 weeks there was no statistical difference in stiffness or strength of the phenytoin treated fractures compared to controls.
Conclusions: The study phenytoin formulations whilst apparently promoting neovascularisation in the healing tendon, did not augment healing strength in either tissue suggesting that at these doses and dosing schedules the role of phenytoin is limited in these tissues.
The abstracts were prepared by Emer Agnew, Secretary to the IOA. Correspondence should be addressed to him at Irish Orthopaedic Association Secretariat, c/o Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
