Open-Label Interventional Study in Healthy Volunteers to Evaluate NO-Mediated Vasodilation by Dermal Allyl Isothiocyanate Challenge and Whole-Body Heat Stress

Abstract: Dermal allyl isothiocyanate (AITC) administration and whole-body heat stress (WBHS) are two challenge models that are used to evaluate physiological mechanisms of vasodilation and pharmacological activity in humans. Their exact vasodilatory mechanisms in humans are not fully elucidated but are likely to be nitric oxide (NO)-mediated. This study aimed to evaluate whether there is overlap in the vasodilatory pathways of dermal AITC application and WBHS by combining the challenges. In this open-label interventional study, healthy volunteers underwent dermal administration of AITC twice: under basal conditions and during WBHS. Dermal blood flow (DBF) was non-invasively measured using laser speckle contrast imaging four times, once in each of the following situations: baseline, WBHS only, AITC only, and WBHS combined with AITC. A total of 12 male volunteers, aged 18– 61 years, participated in the study. Compared to baseline, following AITC application, their DBF increased by 63.43 AU (baseline: 32.55, 95% CI [17.78, 47.31] AU, AITC only: 95.97, 95% CI [81.21, 110.7] AU, p < 0.0001). During WBHS, the increase in DBF after AITC was 42.76 AU (WBHS only: 87.25, 95% CI [72.49, 102.0] AU, WBHS+AITC: 130.0, 95% CI [115.2, 144.8] AU, p < 0.0001). The combination of WBHS and AITC resulted in a lower DBF than the sum of the DBF responses to AITC and WBHS when applied separately (ED 20.67, 95% CI [− 3.532, 44.88], p = 0.0916). This might point towards the presence of an interaction in the vasodilatory mechanism of AITC application and WBHS, possibly indicating overlap in their NOS-driven vasodilatory pathways. Keywords: clinical study, vasodilatory pathways, laser speckle contrast imaging, pharmacological challenge models