Acetylcholine chloride as a potential source of variability in the study of cutaneous vascular function in man

作者:Sauvet Fabien*; Mahe Guillaume; Chennaoui Mounir; Langrume Christophe; Vasseur Melanie; Abraham Pierre; Leftheriotis Georges
来源:Microvascular Research, 2011, 82(2): 190-197.
DOI:10.1016/j.mvr.2011.05.001

摘要

Introduction: Laser-Doppler flowmetry (LDF) coupled with acetylcholine chloride (ACh) iontophoresis is increasingly recognized as a reliable non-invasive method to study the endothelial function. However, ACh-vasodilation measurement appears highly variable possibly due to the ACh pharmacological properties itself. These problems may be partially overcome by using methacholine chloride (MCh), a more stable synthetic agonist of muscarinic receptors, instead of ACh. Therefore, we first studied the correlation between the two drugs and then the effects of (1) spatial variability (inter-site measurements), (2) temporal variability (interday measurements), (3) intra-day variability (morning versus evening), and (4) age on the variability of both ACh-vasodilation and MCh-vasodilation.
Methods: The endothelium-dependent vasodilation response to simultaneous iontophoretic applications (4 doses of 10 s at 0.1 mA with 2 min of current-free interval) of ACh (11 mM) or MCh (10 mM) was studied on the forearm of 40 healthy subjects (36 males, median 28 yr. range 21-59 yr). The percent change in perfusion (CVCpeak) from baseline and the area under the curve (CVCAUC) during iontophoresis were assessed. Inter-site, inter-day and intra-day coefficients of variation (CV) were studied for each drug as well as correlations between drugs and age.
Results: A linear relationship was found between ACh- and MCh-CVCpeak (r(2)=0.75, p=0.01) and between ACh- and MCh-CVCAUC (r(2)=0.55, p=0.02). MCh inter-site CV for both CVCpeak (12.2%) and CVCAUC (13.8%) was significantly lower than ACh inter-site CV for CVCpeak (15.5%) and CVCAUC (15.3%), respectively. MCh inter-day CV for CVCpeak (17.2%) and CVCAUC (14.6%) was significantly lower than ACh inter-day CV for CVCpeak (19.7%) and ACh CVCAUC (21.2%). For ACh and MCh, the CVCpeak and CVCAUC were higher at 16:00 pm than at 11:00 am (p<0.05 for all). Finally, both ACh- and MCh-CVCpeak exhibited a logarithmic decrease with age (r(2)=0.61, p<0.01 and r(2)=0.58, p<0.01).
Conclusion: Although both drugs exhibited circadian and age variability, MCh exhibited less inter-site and interday variabilities than did ACh for the evaluation of cutaneous endothelium-dependent vasodilation. These findings should be taken into account in studies of cutaneous vascular function by iontophoresis coupled with laser Doppler flowmetry.

  • 出版日期2011-9