Improved Hemocompatibility of Silicone Rubber Extracorporeal Tubing via Solvent Swelling-Impregnation of S-Nitroso-N-acetylpenicillamine (SNAP) and Evaluation in Rabbit Thrombogenicity Model

摘要

Blood-contacting devices, including extracorporeal circulation (ECC) circuits, can suffer from complications due to platelet activation and thrombus formation. Development of nitric oxide (NO) releasing polymers is one method to improve hemocompatibility, taking advantage of the ability of low levels of NO to prevent platelet activation/adhesion. In this study a novel solvent swelling method is used to load the walls of silicone rubber tubing with the NO donor S-nitroso-N-acetylpenicillamine (SNAP). This SNAP-silicone rubber tubing exhibits an NO flux of ca. 1 × 10⁻¹⁰ mol cm⁻² min⁻¹, which mimics the range of NO release from the normal endothelium, which is stable for at least 4 h. Images of the tubing before and after swelling, obtained via scanning electron microscopy, demonstrate that this swelling method has little effect on the surface properties of the tubing. The SNAP-loaded silicone rubber and silicone rubber control tubing are used to fabricate ECC circuits that are evaluated in a rabbit model of thrombogenicity. After 4 h of blood flow, the SNAP-loaded silicone rubber circuits were able to preserve the blood platelet count at 64% of baseline (vs. 12% for silicone rubber control). A 67% reduction in the degree of thrombus formation within the thrombogenicity chamber was also observed. This study demonstrates the ability to improve the hemocompatibility of existing/commercial silicone rubber tubing via a simple solvent swelling-impegnation technique, which may also be applicable to other silicone-based blood-contacting devices.