Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

David Silverman


Transdermal microvascular studies of endothelial cell function have typically used iontophoresis to facilitate acetylcholine absorption, but iontophoresis introduces an important confounding stimulus that can alter the behavior of the microvasculature. This study examines a non-iontophoretic technique for transdermal microvascular studies using acetylcholine and nitroglycerin and demonstrates a relatively impaired vasodilatory response to these substances in a population with known microvascular pathology. Ten subjects without known vascular disease or diabetes were recruited for laser Doppler flowmetry (LDF) monitoring. Topical acetylcholine chloride, nitroglycerin, and placebo were applied to subjects foreheads directly below LDF probes. Readings increased by averages of 406% (245%-566%) and 36% (26%-46%), respectively, at the acetylcholine and placebo sites (p=0.005 by Wilcoxon Signed Rank Test (WSRT)); and they increased by 365% (179%-550%) at the nitroglycerin site (p=0.005 by WSRT versus placebo; p=0.6 versus acetylcholine). Ten diabetic subjects were also monitored. Mean percent increases in blood flow were 156% (91%-221%) and 116% (79%-153%), respectively, at the acetylcholine and nitroglycerin sites, vs. 21% (CI 4-37%) at the placebo site (p=0.005 by WSRT for placebo versus each active site). Diabetics responses at both active sites were significantly impaired relative to healthy subjects (p<0.001 and p=0.009, respectively, by Mann-Whitney U Test) Topical acetylcholine and nitroglycerin induced significant local vasodilatory responses without requiring iontophoresis in both healthy and diabetic subjects. Diminished responses were noted in diabetic patients. This technique may constitute a minimally invasive way to interrogate the microvasculature including its responses in various disorders and the microcirculatory changes induced by therapeutic interventions.