Topical non-iontophoretic application of acetylcholine and nitroglycerin via a translucent patch: a new means for assessing microvascular reactivity.
OBJECTIVE
Assessments of endothelial cell function with acetylcholine have typically used systemic, regional intra-arterial, or iontophoretic delivery of drug. Each of these techniques induces systemic and/or local changes that compromise their safety or effectiveness. Using translucent drug preparations applied under laser Doppler flowmetry (LDF) probes, we tested whether local vasodilation can be induced with non-iontophoretic transdermal delivery of acetylcholine and how such dilation would compare to the dilation achieved with topical nitroglycerin in healthy volunteers.


METHODS
Ten subjects without known vascular disease were recruited for LDF monitoring at sites of drug application for this preliminary investigation. Topical acetylcholine chloride, nitroglycerin, and placebo were applied via translucent patches to the forehead directly below LDF probes.


RESULTS
LDF readings increased by 406 percent (245 percent to 566 percent) and 36 percent (26 percent to 46 percent), respectively, at the acetylcholine and placebo sites (p = .005 by Wilcoxon Signed Rank Test (WSRT) for acetylcholine vs. placebo); and they increased by 365 percent (179 percent to 550 percent) at the nitroglycerin site (p = .005 by WSRT for nitroglycerin vs. placebo; p = .6 vs. acetylcholine).


CONCLUSIONS
Transdermal delivery of acetylcholine can induce significant local vasodilatory responses comparable to those achieved with nitroglycerin without requiring iontophoresis. The means of transdermal delivery and monitoring described herein may constitute a new minimally invasive way to interrogate the microvasculature and thereby assess the microcirculatory changes induced by various disorders and therapeutic interventions.
Schonberger
Robert B
RB
Doris Duke Clinicial Research, Yale University School of Medicine, 333 CedarStreet, New Haven, CT 06510, USA.
Worden
William S
WS
Shahmohammadi
Kaveh
K
Menn
Kirsten
K
Silverman
Tyler J
TJ
Stout
Robert G
RG
Shelley
Kirk H
KH
Silverman
David G
DG
D000109:Acetylcholine / Q000008:administration & dosage*; D000287:Administration, Topical; D000328:Adult; D001458:Bandages; D001783:Blood Flow Velocity / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry / Q000379:methods*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D005996:Nitroglycerin / Q000008:administration & dosage*; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012879:Skin Physiological Phenomena / Q000187:drug effects; D014652:Vascular Diseases / Q000175:diagnosis; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D005996:Nitroglycerin; D000109:Acetylcholine