TY - JOUR
T1 - Effects of vehicle microdialysis solutions on cutaneous vascular responses to local heating
AU - Smith, Caroline J.
AU - Craighead, Daniel H.
AU - Alexander, Lacy M.
N1 - Publisher Copyright:
© 2017 the American Physiological Society.
PY - 2017/12
Y1 - 2017/12
N2 - 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 (%CVCmax, sodium nitroprusside and 43°C local heat). The SCB-HCl solution increased baseline %CVCmax (control: 9.7 ± 0.8; SCB-HCl: 21.5 ± 3.5%CVCmax; 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.
AB - 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 (%CVCmax, sodium nitroprusside and 43°C local heat). The SCB-HCl solution increased baseline %CVCmax (control: 9.7 ± 0.8; SCB-HCl: 21.5 ± 3.5%CVCmax; 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.
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U2 - 10.1152/japplphysiol.00498.2017
DO - 10.1152/japplphysiol.00498.2017
M3 - Article
C2 - 28860170
AN - SCOPUS:85038618510
SN - 8750-7587
VL - 123
SP - 1461
EP - 1467
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 6
ER -