Effects of vehicle microdialysis solutions on cutaneous vascular responses to local heating

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 years) 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). Following 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_max, sodium nitroprusside and 43°C local heat). The SCB-HCL solution increased baseline %CVC_max (control: 9.7 ± 0.8, SCB-HCL: 21.5 ± 3.5 %CVC_max; 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.

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