Department of Health and Exercise Science, Appalachian State University, Boone, North Carolina.
Department of Kinesiology, Noll Laboratory, The Pennsylvania State University , University Park, Pennsylvania.
J Appl Physiol (1985). 2017 Dec 1;123(6):1461-1467. doi: 10.1152/japplphysiol.00498.2017. Epub 2017 Aug 31.
Microdialysis is a minimally invasive technique often paired with laser Doppler flowmetry to examine cutaneous microvascular function, yet presents with several challenges, including incompatibility with perfusion of highly lipophilic compounds. The present study addresses this methodological concern, with an emphasis on the independent effects of commonly used vehicle dialysis solutions to improve solubility of pharmacological agents with otherwise low aqueous solubility. Four microdialysis fibers were placed in the ventral forearm of eight subjects (4 men, 4 women; 25 ± 1 yr) with sites randomized to serve as 1) control (lactated Ringer's), 2) Sodium carbonate-bicarbonate buffer administered at physiological pH [SCB-HCl; pH 7.4, achieved via addition of hydrochloric acid (HCl)], 3) 0.02% ethanol, and 4) 2% dimethyl sulfoxide (DMSO). After baseline (34°C), vehicle solutions were administered throughout a standardized local heating protocol to 42°C. Laser Doppler flowmetry provided an index of blood flow. Cutaneous vascular conductance was calculated and normalized to maximum (%CVC, sodium nitroprusside and 43°C local heat). The SCB-HCl solution increased baseline %CVC (control: 9.7 ± 0.8; SCB-HCl: 21.5 ± 3.5%CVC; P = 0.03), but no effects were observed during heating or maximal vasodilation. There were no differences with perfusion of ethanol or DMSO at any stage of the protocol ( P > 0.05). These data demonstrate the potential confounding effects of some vehicle dialysis solutions on cutaneous vascular function. Notably, this study provides evidence that 2% DMSO and 0.02% ethanol are acceptable vehicles with no confounding local vascular effects to a standardized local heating protocol at the concentrations presented. NEW & NOTEWORTHY This study examined the independent effects of common vehicle solutions on cutaneous vascular responses. A basic buffer (SCB-HCl) caused baseline vasodilation; 2% DMSO and 0.02% ethanol had no effects. This highlights the need for considering potential confounding effects of solubilizing solutions when combined with low aqueous soluble pharmacological agents. Importantly, DMSO and ethanol do not appear to influence cutaneous vascular function during baseline or local heating at the concentrations studied, allowing their use without confounding effects.
微透析是一种微创技术，常与激光多普勒流量metry 联合使用，以检查皮肤微血管功能，但存在几个挑战，包括与高度亲脂化合物的灌注不兼容。本研究解决了这一方法学问题，重点是常用载体透析溶液的独立作用，以提高水溶性差的药理学药物的溶解度。将四根微透析纤维放置在八位受试者的前臂腹侧（4 名男性，4 名女性；25 ± 1 岁），将部位随机分为 1）对照（乳酸林格氏液）、2）生理 pH 下的碳酸钠-碳酸氢盐缓冲液[SCB-HCl；通过添加盐酸（HCl）达到 pH 7.4]、3）0.02%乙醇和 4）2%二甲基亚砜（DMSO）。在基线（34°C）后，在标准化局部加热方案下向载体溶液中添加 42°C。激光多普勒流量metry 提供了血流指数。计算皮肤血管传导率，并归一化为最大（%CVC，硝普钠和 43°C 局部热）。SCB-HCl 溶液增加了基线%CVC（对照：9.7 ± 0.8；SCB-HCl：21.5 ± 3.5%CVC；P = 0.03），但在加热或最大血管扩张期间没有观察到效果。在方案的任何阶段，乙醇或 DMSO 的灌注均无差异（P > 0.05）。这些数据表明，一些载体透析溶液对皮肤血管功能有潜在的混杂影响。值得注意的是，本研究提供了证据，证明 2% DMSO 和 0.02%乙醇在呈现的浓度下，在标准化局部加热方案中，是可接受的载体，对局部血管无混杂影响。
本研究检查了常见载体溶液对皮肤血管反应的独立影响。基本缓冲液（SCB-HCl）引起基线血管扩张；2% DMSO 和 0.02%乙醇没有影响。这突出表明，当与低水溶性药理学药物结合使用时，需要考虑增溶剂的潜在混杂影响。重要的是，在研究浓度下，DMSO 和乙醇似乎不会影响基线或局部加热期间的皮肤血管功能，允许在没有混杂影响的情况下使用它们。
