Assessing The Potential Of Nitric Oxide In The Diabetic Foot

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Having the patient take the dietary supplement Arginaid (a precursor to nitric oxide) twice a day helped to foster a significant progression of granulation tissue as shown above. (Photo courtesy of Denise Levy, DPM and John Steinberg, DPM)
Assessing The Potential Of Nitric Oxide In The Diabetic Foot
Having the patient take the dietary supplement Arginaid (a precursor to nitric oxide) twice a day helped to foster a significant progression of granulation tissue as shown above. (Photo courtesy of Denise Levy, DPM and John Steinberg, DPM)
Here one can see the biochemical process of the conversion of arginine to citrulline with the production of nitric oxide. Note that nitric oxide synthase is the key enzyme in this process.
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Author(s): 
By Paul J. Kim, DPM

   There are other concerns regarding the application of higher doses of topical nitroglycerin. There is a possibility that they increase the risk for systemic effects. Patients who suffer from chronic wounds often suffer from other disease processes including cardiac disease. There may be a potential interaction with other cardiac drugs and nitroglycerin at higher doses. There may also be unwanted direct effects on the heart. Accordingly, do these risks outweigh the potential benefits of the topical application of nitroglycerin?

   Another important question is whether NO has positive effects on wounds in the non-ischemic foot. If a patient has adequate blood flow, can augmentation of NO facilitate wound healing? We know that NO plays a role in inflammation. However, the specifics of this role in the chronic wound environment of a diabetic foot are not clear. Researchers have demonstrated that supplementation with exogenous nitric oxide donors such as molsidomine or supplementation of the substrate L-Arginine promotes wound healing in diabetic rats.20,21 However, there is some evidence to suggest that high levels of NO can be destructive to tissues.7 Some also argue that with the potential harmful effects of NO, future research efforts should develop therapies to inhibit NO production.22 Direct application in a controlled study would better delineate the ability of NO to facilitate healing.

   Nitric oxide plays an important role in the vascular system and the inflammatory process. However, we need more data in order to better understand the place of NO in the armamentarium for the treatment of pathologies in the diabetic foot.

Dr. Kim is an Assistant Professor at the Arizona Podiatric Medicine Program, Midwestern University College of Health Sciences. He is the author of multiple clinical and basic science publications and has lectured throughout the country.

Dr. Steinberg (pictured) is an Assistant Professor in the Department of Surgery at the Georgetown University School of Medicine in Washington, D.C. He is a Fellow of the American College of Foot and Ankle Surgeons.




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