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

Is There A Role For Topical Nitroglycerin In Diabetic Wounds?

   However, the direct application of NO for the treatment of diabetic wounds has not been well researched. While it is possible to prevent wound occurrence by reversing or retarding the neuropathic process that often leads to wounds, the question remains on whether NO can expedite the healing of existing wounds.

   There is anecdotal evidence to support this theory. In regard to isosorbide dinitrate (nitroglycerin), a liberator of NO, podiatric physicians have been using topical nitroglycerin to treat ischemic wounds. There are two published studies demonstrating that topical application of nitroglycerin in the form of a paste may increase perfusion to the foot.16,17 Further, a study conducted by Wheeland, et. al., demonstrated that the application of nitroglycerin led to healing of ischemic digital ulcerations.18 However, these studies were small with non-stringent methodology. No systematic, large-scale study has evaluated the efficacy of topical nitroglycerin application in wound healing in the lower extremity. We have submitted for publication a placebo-controlled, randomized, double-blind study evaluating the ability of topical nitroglycerin to measurably increase perfusion to the foot.19 We examined the use of a nitroglycerin patch on healthy subjects and measured perfusion levels using transcutaneous thermometry and photoplethysmography. Our study revealed that nitroglycerin at a low dose does not measurably increase local perfusion. We did not examine higher doses due to potential side effects including headache and dizziness.

   A follow-up study is needed to examine the use of topical nitroglycerin in the lower extremity. Specifically, a placebo-controlled study is required to examine the ability of nitroglycerin to expedite wound healing in the diabetic foot.

In Conclusion

   Some fundamental questions remain regarding the clinical application of NO in wound healing. In our study, we were unable to demonstrate that topical application of nitroglycerin is able to increase perfusion to the foot. However, it is possible that topical application of nitroglycerin can increase local perfusion at higher doses. Assuming that topical nitroglycerin is able to increase local perfusion in the foot, would this increase be able to overcome large vessel compromise upstream?

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