No Flux Determines Thromboresistance in No-Releasing Extracorporeal Circuits

Introduction: NO flux for normal endothelium is 4.0 × 10−10mol/min*cm2. Diazeniumdiolates are typical NO release agents that when incorporated into d matrix polymer prevent platelet adherence and consumption during extracorporeal circulation (ECC). Determining the NO flux necessary to prevent platelet activation during ECC would obviate the need for systemic heparinization. Methods: Two experimental models were used to test a diamino-silica NO donor compound. Initial studies were performed using our rabbit model of ECC. Once efficacy of the coating was demonstrated a 24 hr swine model was used to determine the relationship between circuit NO flux and platelet consumption. Blood samples for both studies included arterial blood gases, platelet counts and platelet aggregometry. NO fluxes and SEMs were performed on all circuits.Figure: Fumed Slica Controls vs ND-Doped in Rabbit model of ECCFigure: Platelet Consumption vs NO Flux in a 24 hr Swine ModelResults: In the rabbit model, the NO-doped circuits demonstrated a trend toward less platelet consumption while SEMs showed less adhesion In the 24 hr swine model platelet consumption was less than expected for the first 12 hours until NO flux fell close to 4.0 × 10−10mol/min*cm2. Conclusion: Maintenance of NO flux greater than endothelial level is a critical component in the development of thromboresistive biomaterials for extracorporeal circulation.