Characterization and in vivo performance of nitric oxide-releasing extracorporeal circuits in a feline model of thrombogenicity

Infection and thrombosis are the two leading complications associated with blood contacting medical devices, and have led to the development of active materials that can delivery antibiotics or antithrombotic agents. Two key characteristics of these materials are the ability to produce controlled delivery, as well as minimal systemic delivery of the agent outside of the device site. Nitric oxide (NO) releasing materials are attractive as NO plays pivotal roles in the body's natural defense against bacterial infection, as well as regulation of platelet adhesion and activation. This work characterizes an NO-releasing extracorporeal circuit (ECC) under flow conditions for the first time, examining the effect of incubation and application of the top coating on leaching of NO donor and NO-release kinetics. Top coated ECCs with incubation delivered ca. 1% of the total NO potential over the 4-h period, whereas uncoated ECCs delivered over 4.5% of the total NO. Incubated ECC loops maintained a flux of 1.83 +/- 0.50 x 10(-10) mol min(-1) cm(-2) for the full 4 h duration. The NO-releasing ECC loops significantly increased the time-to-clot as compared to the corresponding control (11 +/- 3.6 min control, 132 +/- 93.0 min NO-releasing) when evaluated in vivo in a feline animal model. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 539-546, 2017.