Nitric Oxide: What a Vascular Surgeon Needs to Know

Daniel A. Popowich; Vinit Varu; Melina R. Kibbe


Vascular. 2007;15(6):324-335. 

In This Article

Future Directions

As stated earlier, one main limitation of local drug delivery is the finite amount of drug that can be delivered. NOS gene therapy has proved to be able to increase the duration of bioavailability but has its own host of side effects that have caused the field to fall out of favor. Because of these limitations, new materials have been developed that rely on using endogenous S-nitrosothiols that already circulate in our blood as an infinite local source of NO.[58]

One of the first studies to describe this was performed by Duan and Lewis.[76]l-Cysteine was immobilized onto both polyethylene terephthalate (Dacron) and polyurethane. l-Cysteine has been demonstrated to catalyze NO release from S-nitrosoalbumin (AlbSNO), an endogenous S-nitrosothiol. l-Cysteine immobilized on this polymer promotes transnitrosation of NO from AlbSNO to the immobilized l-cysteine. The NO is then quickly released owing to its instability. In vitro testing showed that these polymers exhibited up to 65% reduced platelet adherence. The authors speculated that this mechanism could be used to improve the hemocompatibility of many different blood-contacting devices.[76,77] This has yet to be tested in animal models.

Another example of using endogenous S-nitrosothiols as local NO donors was described by Oh and Meyerhoff.[78] The authors exploited one of the known mechanisms by which S-nitrosothiols release NO, using copper as a catalyst. They developed a biomimetic lipophilic copper complex that is able to reduce S-nitrosothiols and nitrite to NO under physiologic conditions. This complex was doped into polyvinyl chloride and polyurethane films and was shown to catalytically generate NO. The advantage of employing this catalytic surface in vivo is that locally enhanced NO levels are likely to be maintained for extended periods of time by reaction with endogenous S-nitrosothiol compounds that exist in human blood. The authors speculated that this could be used to overcome biocompatibility problems for long-term vascular implants, such as stents and vascular grafts.

Recently,Wu and colleagues attempted to use this same technology when applied to intravascular oxygen sensors.[79] Metallic copper particles were embedded as catalysts into thin polymer coatings on the surface of intravascular electrochemical oxygen-sensing catheters. These catheters were tested in vivo by implanting them into porcine carotid arteries. The NO-releasing catheters exhibited less thrombosis and obtained more accurate measurements compared with control sensors. The authors speculated that because of the improved biocompatibility of these products and their ability to produce NO continuously, this approach could be used with any blood-contacting device.

In the attempt to improve on this technology, Cha and Meyerhoff described the first NO-generating material that uses an immobilized organoselenium moiety as a catalyst for endogenous S-nitrosothiol decomposition.[80] Organoselenium compounds can generate NO from S-nitrosothiols via a catalytic reaction similar to copper. The authors stated that polymers containing immobilized organoselenium species appear to be the most promising as new NO-generating materials for implantation purposes. Yet, at this time, there have been no published studies examining their use to reduce neointimal hyperplasia in animals.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.