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A Human Vascular Model Based on Microdialysis for the Assessment of the Vasoconstrictive Dose-Response Effects of Norepinephrine and Vasopressin in Skin
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL.
Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
AB Biopharmacon, Uppsala.
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2012 (English)In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 19, no 4, 352-359 p.Article in journal (Refereed) Published
Abstract [en]

Abstract Objective: 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. Methods: We investigated whether increasing concentrations of norepinephrine (NE, 1.859 mu mol/L) and vasopressin (VP, 1100 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). Results: 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 andlt; 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 andlt; 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. Conclusions: 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.

Place, publisher, year, edition, pages
Informa Healthcare / John Wiley and Sons , 2012. Vol. 19, no 4, 352-359 p.
Keyword [en]
microdialysis, urea, skin, noradrenalin, vasopressin, dose-response, pharmacodynamics, human, vasoconstriction
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-77530DOI: 10.1111/j.1549-8719.2012.00170.xISI: 000303159500008OAI: oai:DiVA.org:liu-77530DiVA: diva2:528605
Note

Funding Agencies|Berzelius Clinical Research Center AB, Linkoping, Sweden||

Available from: 2012-05-28 Created: 2012-05-22 Last updated: 2017-12-07

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Samuelsson, AndersTesselaar, ErikSjöberg, Folke

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Department of Clinical and Experimental MedicineFaculty of Health SciencesAnesthesiologyDepartment of Intensive Care UHLBurn CenterDepartment of Plastic Surgery, Hand surgery UHLDepartment of Anaesthesiology and Surgery UHL
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