Elsevier

Medical Hypotheses

Volume 83, Issue 2, August 2014, Pages 172-174
Medical Hypotheses

Treatment with topical nitroglycerine may promote the healing process of diabetic foot ulcers

https://doi.org/10.1016/j.mehy.2014.05.002Get rights and content

Abstract

Diabetes mellitus is one of the main problems of the health care systems of all societies. A vast number of diabetic patients suffer from diabetic foot ulcers (DFUs) some of which may lead to the amputation of the organ(s). Nitric oxide (NO) is an indigenous gas that is produced at various sites in the body and has been shown to possess important roles in wound healing. Previous studies have shown that not only is the production of NO decreased in diabetic patients but also the sensitivity of the cells of such patients to NO is dramatically reduced. Nitroglycerine (isosorbide dinitrate) can be employed as an effective donor of NO to diabetic wounds. On such a basis, we suggest a novel hypothesis that delivery of compensatory amounts of NO to the ulcers by the administration of topical nitroglycerine enhances blood flow and biochemical activity of the ulcers and thus promotes wound healing.

Introduction

Diabetes mellitus is one of the main problems of health care systems of all societies. The number of people with diabetes worldwide was estimated at 131 million in 2000; it is projected to increase to 366 million by 2030 [1]. One of the most important problems that people with diabetes mellitus face, are the ulcerations that appear in their lower extremities which in some cases may lead to amputation with a prevalence of 4–10% if proper care is not taken [2]. More than 80,000 amputations are performed each year on diabetic patients in the United States [1]. Routine ulcer care, treatment of infections, amputations, and hospitalizations cost billions of dollars every year and place a tremendous burden on the health care systems. Diabetic foot ulcers (DFUs) result from simultaneous action of multiple contributing causes. The major underlying causes are peripheral ischemia resulting from peripheral vascular disease and neuropathy [1], [3]. These vascular modifications are the key points in pathogenesis of diabetes and are the main issue of relevant research. NO is an indigenous gas that is made at various sites in the body and performs important functions in the process of wound healing [4].

Section snippets

Background

There are multiple factors that contribute to the initiation of DFUs. Peripheral vascular complications such as ischemic conditions are the main causes responsible for the development of the ulcers [1], [2]. Endothelial cell dysfunction may occur as a result of persistent hyperglycemia that finally leads to the resultant decrease in endothelium-derived nitric oxide. This decrease in the production of nitric oxide is mainly due to a deficiency in nitric oxide synthase in diabetic patients. On

Hypothesis

Based on the previous studies stated above, we present a novel hypothesis which can be considered as an effective therapeutic approach in the treatment of DFUs. NO has a prominent role in the inflammatory phase of wound healing. On the other hand, NO release from endothelial cells is dramatically decreased in diabetic patients. During the wound healing process, topical application of nitroglycerine as a synthetic and safe NO releasing agent onto the site of ulcers could be recruited to deliver

Discussion

The effect of NO on the healing process of ulcers consists of two main compartments. First of all is the effect of NO on the vasculature of the wounds. It causes vasodilation in both arteries and veins. On the other hand, the inhibition of NO synthesis leads to vasoconstriction and an increase in blood pressure as a result [8]. The hyperglycemic condition present in diabetic patients damages the endothelial cells. There is evidence regarding the decrease of NO production in diabetic mice models

Conclusion

These data all together suggest that administration of topical nitroglycerine can foster the amelioration of DFUs via donating compensatory amounts of NO to the site of ulcers. This may target the ischemia caused by peripheral vascular disease which is among the multiple causes for the development of DFUs. However, proper in vitro studies and clinical trials are required herein to precisely define the feasibility of this hypothesis as applicable for therapeutic purposes.

Conflict of interest statement

None declared.

Acknowledgment

None.

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