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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
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för medicin och hälsa, Anestesiologi med intensivvård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Intensivvårdskliniken US.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Brännskadevård. Linköpings universitet, Hälsouniversitetet.
AB Biopharmacon, Uppsala.
Vise andre og tillknytning
2012 (engelsk)Inngår i: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 19, nr 4, s. 352-359Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Informa Healthcare / John Wiley and Sons , 2012. Vol. 19, nr 4, s. 352-359
Emneord [en]
microdialysis, urea, skin, noradrenalin, vasopressin, dose-response, pharmacodynamics, human, vasoconstriction
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-77530DOI: 10.1111/j.1549-8719.2012.00170.xISI: 000303159500008OAI: oai:DiVA.org:liu-77530DiVA, id: diva2:528605
Merknad

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

Tilgjengelig fra: 2012-05-28 Laget: 2012-05-22 Sist oppdatert: 2017-12-07

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Samuelsson, AndersTesselaar, ErikSjöberg, Folke

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