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Randomized Controlled Trial Multicenter Study
A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of norepinephrine and vasopressin in skin.
- Kim Tchou Folkesson, Anders Samuelsson, Erik Tesselaar, Bengt Dahlström, and Folke Sjöberg.
- Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
- Microcirculation. 2012 May 1;19(4):352-9.
ObjectiveMicrodialysis 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.MethodsWe 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).ResultsWe 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.ConclusionsMicrodialysis 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.© 2012 John Wiley & Sons Ltd.
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