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A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of noradrenaline and vasopressin in skin: in JOURNAL OF VASCULAR RESEARCH, vol 48, pp 320-320
Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Uppsala, Sweden,.
Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Berzelius Clinical Research Center, Linköping, Sweden.
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2011 (English)In: JOURNAL OF VASCULAR RESEARCH, Karger , 2011, 320-320 p.Conference paper (Refereed)
Abstract [en]

Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the Emax model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.

Place, publisher, year, edition, pages
Karger , 2011. 320-320 p.
Keyword [en]
Microdialysis; Urea; Skin; Noradrenalin; Vasopressin; micro dose; dose-response; pharmacodynamics; human; vasoconstriction
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-59518ISI: 000294760800317OAI: diva2:351998
Available from: 2010-09-17 Created: 2010-09-17 Last updated: 2012-03-21Bibliographically approved
In thesis
1. Effects of burns and vasoactive drugs on human skin: Clinical and Experimental studies using microdialysis
Open this publication in new window or tab >>Effects of burns and vasoactive drugs on human skin: Clinical and Experimental studies using microdialysis
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients who require critical care, including those with burns, are affected by a systemic inflammatory reaction, which at times has consequences such as multiple organ dysfunction and failure. It has become increasingly evident that other factors important in the development of organ dysfunction are disturbances at the tissue level, in the microcirculation. Such disturbances activate cascade systems including stress hormones, all of which have local effects on organ function.

Despite this knowledge, monitoring and treatment in critical illness today relies mainly on central haemodynamics and blood sampling.

Microdialysis is a minimally invasive technique that enables us to study the chemical composition and changes in biochemistry in the extracellular, extravascular space in living tissues. Most of our current experience is from animal models, but the technique has also been used in humans and has become routine in many neurosurgical intensive care units to monitor brain biochemistry after severe injury. In skin, this experience is limited. During the first half of this thesis we studied the injured and uninjured skin of severely burned patients. The results show that there are severe local metabolic disturbances in both injured and uninjured skin. Most interesting is a sustained tissue acidosis, which is not detectable in systemic (blood) sampling. We also recorded considerable alterations in the glucose homeostasis locally in the skin, suggesting a cellular or mitochondrial dysfunction. In parallel, we noted increased tissue glycerol concentrations, which indicated appreciable traumainduced lipolysis.

We also examined serotonin kinetics in the same group of patients, as serotonin has been claimed to be a key mediator of the vasoplegia and permeability disturbances found in patients with burns. We have shown, for the first time in humans to our knowledge, that concentrations of serotonin in skin are increased tenfold, whereas blood and urine concentrations are just above normal. The findings support the need for local monitoring of substances with rapid local reabsorption, or degradation, or both. The results also indicate that serotonin may be important for the systemic response that characterises burn injuries.

In the second half of the thesis we evaluated the effects of microdosing in skin on metabolism and blood flow of vasoactive, mainly stress-response-related, drugs by the microdialysis system. The objectives were to isolate the local effects of the drugs to enable a better understanding of the complex relation between metabolic effects and effects induced by changes in local blood flow. In the first of these two studies we showed that by giving noradrenaline and nitroglycerine into the skin of healthy subjects we induced anticipated changes in skin metabolism and blood flow. The results suggest that the model may be used to examine vascular and metabolic effects induced locally by vasoactive compounds. Data from the last study indicate that conventional pharmacodynamic models (Emax) for time and dose response modelling may be successfully used to measure the vascular and metabolic response in this microdosing model.

We conclude that the microdialysis technique can be successfully used to monitor skin metabolism and iso late a mediator (serotonin) of the local skin response in burned patients. It was also feasible to develop a vascular model in skin based on microdialysis to deliver vasoactive substances locally to the skin of healthy volunteers. This model provided a framework in which the metabolic effects of hypoperfusion and reperfusion in skin tissues could be examined further.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 83 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1195
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-59519 (URN)978-91-7393-342-1 (ISBN)
Public defence
2010-10-08, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Available from: 2010-09-17 Created: 2010-09-17 Last updated: 2012-05-09Bibliographically approved

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Samuelsson, AndersTesselaar, ErikSjöberg, Folke
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AnesthesiologyFaculty of Health SciencesDepartment of Intensive Care UHLDepartment of Anaesthesiology and Surgery UHLDepartment of Clinical and Experimental MedicineBurn CenterDepartment of Plastic Surgery, Hand surgery UHL
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