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Applications of Chemical and Electrochemical Generation in Nitric Oxide (NO)

Speaker: Mark Meyerhoff, Philip J. Elving Collegiate Professor of Chemistry, University of Michigan Location: 402 N Blackford St. Indianapolis, IN 46202 LD 010

Host: Deiss

​Nitric oxide (NO) has many physiologically important properties, including serving as a potent antithrombotic, antimicrobial and anti-inflammatory agent, as well as facilitating angiogenesis and vasodilation.  These properties make NO release/generation potentially useful for developing improved medical devices, including advanced thromboresistant/bactericidal intravascular (IV)/urinary catheters, in vivo chemical sensors, wound healing materials, and infusion cannula, as well as methods to create gas phase NO for inhalation therapy.  In this presentation, recent efforts to develop both chemical and novel electrochemical approaches for controlled generation of NO for use in the development of such biomedical devices/systems will be described.  The most recent and promising chemical-based method involves use of S-nitroso-N-acetylpenicillamine (SNAP) as an NO donor species impregnated into various plastic medical tubing/films.  Devices prepared with SNAP-doped polymers exhibit long-term NO release (up to 1 month), reduced clotting in vivo and significantly less microbial biofilm formation on their surfaces when tested both in vitro and in vivo.  Efforts to adapt this SNAP impregnation technology to reduce the inflammatory response to subcutaneous implants, such as tiny (25 gauge) polymeric insulin pump infusion cannula, are also under investigation.  The electrochemical approach is based on the electro-reduction of inorganic nitrite anions using Cu(II)-ligand complexes as mediators that mimic the active sites of nitrite reductase enzyme.  The temporal pattern of electrochemical NO generation can be precisely modulated/controlled by the magnitude of different applied potentials or currents.  This new electrochemical NO generation chemistry can be readily incorporated within one lumen of multi-lumen intravascular catheters to reduce clotting and infection, and improve the accuracy of intravascular PO2 sensors and potentially other sensors (glucose, lactate, etc.).  The technology can also be adapted for creating flexible antimicrobial wound healing patches.  Further, it will shown that the new electrochemical NO delivery method can also be adapted to develop a novel gas phase NO generator system that can potentially replace the costly NO tanks used currently for inhaled nitric oxide therapy in hospitals to treat pulmonary hypertension, and also to provide NO within the sweep gas of oxygenators used in cardiopulmonary bypass (CPB) surgery to prevent activation of white blood cells that can cause systemic inflammatory response syndrome (SIRS).