Mahé G, Abraham P, Humeau-Heurtier A, Gascoin L, Lefthériotis G, Durand S
Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI) - Unité mixte UMR CNRS 6214 / INSERM U 1083, Faculté de Médecine, Angers, France.
Laboratory of Vascular Investigations, University Hospital of Angers, France.
Br J Clin Pharmacol. 2015 Aug;80(2):185-92. doi: 10.1111/bcp.12623. Epub 2015 May 26.
Current-induced vasodilation (CIV) is an axon-reflex response observed during monopolar current application such as iontophoresis. Cyclo-oxygenase derivates (COD) participate in CIV and act as sensitizing agents at the anodal level. Mechanisms involved during cathodal current application (CCA) are partially unknown. In a randomized double-blind crossover trial, we tested in 16 healthy subjects (i) the influence of the inter-stimulation interval (I-I) by comparing CIV following all-at-once 10 s CCA against 2 × 5 s CCA with intervals ranging from15 s-16 min and (ii) the participation of COD in CIV using 1 g aspirin or placebo intake.
Measurements were repeated 2 h and 14 days after treatment. Laser Doppler flowmetry assessed cutaneous blood flow, reported in multiples of baseline.
Before treatment, peak vasodilation 10 min after the last current application (CVCstim2 ) increased compared with baseline whatever the I-I. Increase in CVCstim2 from baseline was greater for the 4 min (9.4 (5.3, 10.9) times; median (1(st) percentile, 3(rd) percentile)) and higher I-Is compared with all-at-once delivery (3.0 (2.1, 4.3) times, P < 0.05). The response was similar after placebo but aspirin abolished this vasodilation (increase by 1.2 (1.1, 1.3) times for all-at-once delivery and by 1.5 (1.3, 1.7) ± 0.3 times for 4 min interval, 2 h after aspirin intake) that recovered after 14 days.
This confirms the participation of COD in CIV with CCA and their sensitizing action. This model can represent an attractive way to study the axon-reflex and sensitizing function of COD in humans.
电流诱导的血管舒张(CIV)是在诸如离子电渗疗法等单极电流施加过程中观察到的一种轴突反射反应。环氧化酶衍生物(COD)参与CIV并在阳极水平充当敏化剂。阴极电流施加(CCA)期间涉及的机制部分未知。在一项随机双盲交叉试验中,我们在16名健康受试者中测试了:(i)通过比较一次性10秒CCA与间隔时间为15秒至16分钟的2×5秒CCA后的CIV,来研究刺激间隔(I-I)的影响;(ii)使用1克阿司匹林或安慰剂摄入来研究COD在CIV中的作用。
在治疗后2小时和14天重复测量。激光多普勒血流仪评估皮肤血流,以基线倍数报告。
治疗前,无论I-I如何,最后一次电流施加后10分钟的血管舒张峰值(CVCstim2)与基线相比均增加。与一次性给药相比,4分钟(9.4(5.3,10.9)倍;中位数(第1百分位数,第3百分位数))及更长I-I时,CVCstim2相对于基线的增加更大(3.0(2.1,4.3)倍,P<0.05)。安慰剂后反应相似,但阿司匹林消除了这种血管舒张(阿司匹林摄入后2小时,一次性给药增加1.2(1.1,1.3)倍,4分钟间隔增加1.5(1.3,1.7)±0.3倍),14天后恢复。
这证实了COD在CCA诱导的CIV中的参与及其敏化作用。该模型可能是研究人类轴突反射和COD敏化功能的一种有吸引力的方法。