A Rat Model Designed for the Continuous Intraarterial Infusion of Cyclosporine

• We designed a rat model of IA infusion based on the hindlimb replanted model to simulate the limb allotransplantation.
• We infused CSA continuously through a local artery and systemic vein.
• IA infusion can improve the tissue concentrations of CSA compared with systemic infusion.
• This model can be used to study the drug pharmacokinetics of local IA infusion.

BackgroundLimb allotransplantation is not a life-saving treatment. However, large doses of immunosuppressive agents are needed. There is an urgent need to increase the selectivity and targeting of drugs.MethodsWe designed a rat model for intraarterial infusion of cyclosporine (CSA) based on the hindlimb replanted model to simulate the limb allotransplantation. To investigate whether intraartery infusion could improve the drug's distribution, we infused CSA 4.0 mg/kg per day continuously into either the superficial epigastric artery (IA group) or superficial epigastric vein (IV group) of Lewis rats.ResultsOn day 10, CSA concentrations were measured in skin, muscle, and bone tissues of hindlimb. Samples were taken from different parts of the bilateral hindlimbs in the IA group and right hindlimb only in the IV group. Tissue concentrations of the perfusion side were much higher in IA group. Systemic concentrations of IA group were higher than IV group.ConclusionsThese results warrant further research in our next limb allotransplantation model.