Date of Award

January 2011

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

David Silverman

Subject Area(s)

Medicine

Abstract

Abstract

Nicotine can stimulate both sympathetic and parasympathetic ganglionic cells depending on which ganglionic cells of the ANS it is able to access. This study involved the transdermal delivery of low doses of nicotine and nitroglycerin to the forehead and finger microvasculature so as to test the hypothesis that, although both drugs will cause vasodilation at the forehead, the nature of the dilation will differ as a consequence of their different sites of action within the neuro-microvascular pathways. With IRB approval, the local effects of transdermal nitroglycerin and nicotine were investigated on the forehead and finger of 10 healthy volunteers resting supine in a temperature-regulated room (22±1°C). Each micropatch was placed on the forehead and finger beneath a laser Doppler flowmetry (LDF) probe which measured the relative blood flow. The changes in the height (AC) and the baseline (DC) components of the laser Doppler signal were assessed as well as the power of the signal at different frequencies. Both drugs caused significant vasodilation at the forehead vasculature. The increase in the AC component was larger for nicotine than for nitroglycerin. Similarly the DC component showed a larger increase for nicotine than for nitroglycerin. There was no significant increase in either component at the finger. The FFT analysis showed marked oscillatory activity at the nicotine application site for virtually every frequency that we studied up to about 0.3. Both nicotine and nitroglycerin caused vasodilation of the forehead microvasculature while not at the finger. Nicotine may turn out to be the ideal transdermal preparation for testing a disorder such as diabetic neuropathy and the impact of diabetes on endothelium-dependent vasodilation. Since intact postganglionic parasympathetic fibers are required for nicotine to exert its vasodilatory effect on the microvasculature, application of a nicotine micropatch not only would test the vessel but also the post-ganglionic pathway and, hence, potentially identify the autonomic neuropathic component.

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