SkBF values were allowed to return to baseline (in about one hour) and the test was repeated [20] with a plateau selleck chemical response somewhat lower than the first one (94%), a difference that was not statistically significant. In the protocol by Cracowski et al. [4], six subjects were enrolled, three men and three women. The laser-Doppler flowmeter (MoorLAB; Moor Instruments, Devon, UK) was also single point at 780 nm, and associated with integrated local heaters (SH02; Moor Instruments). Heating was carried out to 42°C until SkBF reached a plateau
(30 minutes), on two occasions separated by two hours [4]. Thus, the set of conditions in the present study essentially included those used by both authors, in terms of equipment and timing. And nevertheless, desensitization of the plateau response was systematically observed. The major remaining difference is the much larger size of our study, compared with these others. It must be underscored that the primary aim of these two studies
was not to test the reproducibility of thermal hyperemia. Rather, they were powered to detect effects of locally administered pharmacological agents, with sites that were either untreated [4] or treated with placebo [20] used as controls. The data just cited from these two studies exclusively concern the control sites. With relatively few subjects, the desensitization effect could have been missed, considering the variability of Selleckchem C646 SkBF measured with LDF, which is much higher than with the LDI, as clearly demonstrated by Roustit et al. [18]. Indeed, we carried out a preliminary analysis of our data Levetiracetam after the inclusion of the first 12 subjects (not shown), with results qualitatively similar to those shown in Figures 2 and 3, and statistical significance for desensitization attained on sites evaluated with LDI (p = 0.001), but not with LDF (p = 0.13). Power calculations then induced us to include
16 more subjects to settle the matter and safely conclude that desensitization is not specific to the particular conditions of our previous study. That it took fewer subjects to detect the same effect with LDI than with LDF instrumentation suggests an advantage in terms of study size of using the former, if available, in future studies, which would employ thermal hyperemia as a tool for probing the skin microcirculation in humans. The mechanisms implied in desensitization remain incompletely defined. In our previous study [3], we found that local heating desensitized forearm skin to the vasodilatory effects of NO, as administered exogenously by iontophoresis of sodium nitroprusside, a donor of NO. This effect of local heating was transient, being observed in 2, but not four hours after the thermal challenge. On the basis of this observation, we postulated that local heating could down-regulate NO signaling somewhere downstream from the endogenous production of this mediator.