Reproducibility of laser Doppler imaging of skin blood flow as a tool to assess endothelial function

Endothelial dysfunction might be an important and early event in the pathog enesis of major cardiovascular diseases. Therefore, the evaluation of endot helial function in humans may be of great clinical relevance. Usual methods for that purpose are either invasive and/or technically demanding. In the dermal microcirculation, endothelial function may be assessed noninvasively from the laser Doppler measurement of increases in blood flow after either the transdermal application of acetylcholine by iontophoresis, or the rele ase of transient arterial occlusion (reactive hyperemia). An endothelium-in dependent response may be provided by the iontophoresis of sodium nitroprus side. This approach is notable for technical simplicity, but of uncertain r eproducibility. Sixteen young, healthy, nonsmoking males were examined in t he fasting state. Changes in skin blood flow were measured with a laser Dop pler imager during the iontophoresis of acetylcholine and sodium nitropruss ide, as well as during reactive hyperemia, on two different days, at each o f two different sites on the volar face of the forearm. Nonspecific effects related to the stimulation of terminal nerve fibers by the iontophoretic c urrent were suppressed by prior surface anesthesia. The iontophoresis of ac etylcholine and sodium nitroprusside induced a seven- to eightfold increase in dermal blood flow. The corresponding figure for peak reactive hyperemia was approximately fourfold. The mean coefficients of variation of response s recorded on different days, on the same site, in the same individual were <10% for iontophoresis of acetylcholine and for peak reactive hyperemia, a nd between 10 and 20% for iontophoresis of sodium nitroprusside, This day-t o-day variation was significantly smaller than the site-to-site variation ( p < 0.01 for all three responses). Endothelium-dependent and -independent r esponses of dermal blood flow evaluated with laser Doppler imaging are high ly reproducible from day to day, at least in healthy nonsmoking young male subjects, and provided some simple precautions are observed, foremost among which is the strict standardization of the recording site. These observati ons may have implications for the testing of endothelial function in clinic al studies.