Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Microcirculation. 2012 May;19(4):352-9. doi: 10.1111/j.1549-8719.2012.00170.x.
Microdialysis enables drug delivery in the skin and simultaneous measurement of their effects. The present study aimed to evaluate dose-dependent changes in blood flow and metabolism during microdialysis of norepinephrine and vasopressin.
We investigated whether increasing concentrations of norepinephrine (NE, 1.8-59 μmol/L) and vasopressin (VP, 1-100 nmol/L), delivered sequentially in one catheter or simultaneously through four catheters, yield dose-dependent changes in blood flow (as measured using urea clearance) and metabolism (glucose and lactate).
We found a significant dose-dependent vasoconstriction with both drugs. Responses were characterized by a sigmoid dose response model. Urea in the dialysate increased from a baseline of 7.9 ± 1.7 to 10.9 ± 0.9 mmol/L for the highest concentration of NE (p < 0.001) and from 8.1 ± 1.4 to 10.0 ± 1.7 mmol/L for the highest concentration of VP (p = 0.037). Glucose decreased from 2.3 ± 0.7 to 0.41 ± 0.18 mmol/L for NE (p = 0.001) and from 2.7 ± 0.6 to 1.3 ± 0.5 mmol/L for VP (p < 0.001). Lactate increased from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for NE (p = 0.005) and from 1.1 ± 0.4 to 2.6 ± 0.5 mmol/L for VP (p = 0.008). There were no significant differences between responses from a single catheter and from those obtained simultaneously using multiple catheters.
Microdialysis in the skin, either with a single catheter or using multiple catheters, offers a useful tool for studying dose response effects of vasoactive drugs on local blood flow and metabolism without inducing any systemic effects.
微透析技术可实现药物在皮肤中的递药，并同时测量其效果。本研究旨在评估去甲肾上腺素和血管升压素微透析时血流和代谢的剂量依赖性变化。
我们研究了通过一根导管依次递增大浓度的去甲肾上腺素（NE，1.8-59 μmol/L）和血管升压素（VP，1-100 nmol/L），或者通过四根导管同时递增大浓度的 NE 和 VP 是否会引起血流（以尿素清除率衡量）和代谢（葡萄糖和乳酸）的剂量依赖性变化。
我们发现两种药物均引起显著的剂量依赖性血管收缩。反应特征呈 S 型剂量反应模型。NE 最高浓度时，透析液中尿素从基础值 7.9 ± 1.7 mmol/L 增加至 10.9 ± 0.9 mmol/L（p < 0.001），VP 最高浓度时，透析液中尿素从基础值 8.1 ± 1.4 mmol/L 增加至 10.0 ± 1.7 mmol/L（p = 0.037）。NE 时，葡萄糖从基础值 2.3 ± 0.7 mmol/L 降至 0.41 ± 0.18 mmol/L（p = 0.001），VP 时，葡萄糖从基础值 2.7 ± 0.6 mmol/L 降至 1.3 ± 0.5 mmol/L（p < 0.001）。NE 时，乳酸从基础值 1.1 ± 0.4 mmol/L 增至 2.6 ± 0.5 mmol/L（p = 0.005），VP 时，乳酸从基础值 1.1 ± 0.4 mmol/L 增至 2.6 ± 0.5 mmol/L（p = 0.008）。使用单个导管与使用多个导管同时获得的反应之间没有显著差异。
皮肤中的微透析技术，无论是使用单个导管还是多个导管，都是一种有用的工具，可用于研究血管活性药物对局部血流和代谢的剂量反应效应，而不会引起任何全身效应。
