| 1. |
- Samuelsson, Anders, et al.
(författare)
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Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline
- 2012
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Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 38:7, s. 975-983
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support. less thanbrgreater than less thanbrgreater thanMethod: Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded. less thanbrgreater than less thanbrgreater thanResults: Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine. less thanbrgreater than less thanbrgreater thanConclusion: These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.
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| 2. |
- Farnebo, Simon, et al.
(författare)
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Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times
- 2010
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Ingår i: MICROVASCULAR RESEARCH. - : Elsevier Science B.V., Amsterdam. - 0026-2862. ; 80:3, s. 412-416
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Tidskriftsartikel (refereegranskat)abstract
- Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r = 0.80; RBC concentration: r = 0.94). This correlation increases with longer occlusion durations (1, 5 and 10 min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2) = 0.59; RBC concentration: r(2) = 0.78) and the recovery times (perfusion: r(2) = 0.62; RBC concentration: r(2) = 0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.
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| 3. |
- Folkesson, Tchou, et al.
(författare)
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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
- 2011
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Ingår i: JOURNAL OF VASCULAR RESEARCH. - : Karger. ; , s. 320-320
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Konferensbidrag (refereegranskat)abstract
- 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.
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| 4. |
- Iredahl, Fredrik, et al.
(författare)
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The Microvascular Response to Transdermal Iontophoresis of Insulin is Mediated by Nitric Oxide
- 2013
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Ingår i: Microcirculation. - : WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA. - 1073-9688 .- 1549-8719. ; 20:8, s. 717-723
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveInsulin has direct effects on blood flow in various tissues, most likely due to endothelial NO production. We investigated whether insulin delivered to the skin by iontophoresis increases microvascular perfusion and whether this effect is partly or completely mediated by the release of NO. MethodsIn healthy subjects, regular insulin and monomeric insulin were delivered to the skin by cathodal iontophoresis. The skin was pretreated either with L-NAME or control solution (PBS) using anodal iontophoresis. Microvascular responses were measured using laser Doppler flowmetry. ResultsA dose-dependent increase in perfusion was observed during iontophoresis of regular and monomeric insulin. The maximum perfusion was significantly elevated compared with control after PBS (regular insulin 53.6 (12.7-95.6) PU vs. 4.2 (3.4-4.8) PU, p = 0.002; monomeric insulin 32.6 (8.9-92.6) PU vs. 5.9 (3.4-56.0) PU, p = 0.03). The microvascular response to insulin was abolished after L-NAME (regular insulin: 25.6 (11.6-54.4) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.15; monomeric insulin 10.9 (5.4-56.8) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.22). ConclusionsThe main finding is that iontophoresis of insulin induces a dose-dependent vasodilation in the skin, which could be suppressed after pretreatment with a NO synthase inhibitor. This suggests that vasodilation in the skin after iontophoresis of insulin is mediated by the NO pathway.
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| 5. |
- Li, Y., et al.
(författare)
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Hyperoxia affects the regional pulmonary ventilation/perfusion ratio : an electrical impedance tomography study
- 2014
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 58:6, s. 716-725
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Tidskriftsartikel (refereegranskat)abstract
- Background The way in which hyperoxia affects pulmonary ventilation and perfusion is not fully understood. We investigated how an increase in oxygen partial pressure in healthy young volunteers affects pulmonary ventilation and perfusion measured by thoracic electrical impedance tomography (EIT). Methods Twelve semi-supine healthy male volunteers aged 21-36 years were studied while breathing room air and air-oxygen mixtures (FiO2) that resulted in predetermined transcutaneous oxygen partial pressures (tcPO2) of 20, 40 and 60kPa. The magnitude of ventilation (Zv) and perfusion (ZQ)-related changes in cyclic impedance variations, were determined using an EIT prototype equipped with 32 electrodes around the thorax. Regional changes in ventral and dorsal right lung ventilation (V) and perfusion (Q) were estimated, and V/Q ratios calculated. Results There were no significant changes in Zv with increasing tcPO2 levels. ZQ in the dorsal lung increased with increasing tcPO2 (P=0.01), whereas no such change was seen in the ventral lung. There was a simultaneous decrease in V/Q ratio in the dorsal region during hyperoxia (P=0.04). Two subjects did not reach a tcPO2 of 60kPa despite breathing 100% oxygen. Conclusion These results indicate that breathing increased concentrations of oxygen induces pulmonary vasodilatation in the dorsal lung even at small increases in FiO2. Ventilation remains unchanged. Local mismatch of ventilation and perfusion occurs in young healthy men, and the change in ventilation/perfusion ratio can be determined non-invasively by EIT.
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| 6. |
- Lindahl, Filip, et al.
(författare)
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Assessing paediatric scald injuries using Laser Speckle Contrast Imaging
- 2013
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Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 39:4, s. 662-666
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe use of objective methods for assessment of burns is limited. Laser Speckle Contrast Imaging (LSCI) is a non-invasive technique for instant measurement of tissue perfusion, making it potentially valuable for early prediction of burn wound outcome.AimTo evaluate the influence of technical factors on perfusion and to measure perfusion in burns 0–14 days post-burn and compare this with the outcome of the burn wound at 14 days after burn.MethodThe effect of room light, camera distance and camera angle was studied using a suspension of polystyrene particles. LSCI measurements were performed on 45 scald burns and 32 uninjured areas 0–14 days after burn.ResultTechnical factors had no clinically relevant effect on measured perfusion. Burns that healed within 14 days had a higher perfusion during the first week post-burn than burns that healed after 14 days or underwent surgery. The difference in perfusion was largest 4–7 days after burn.ConclusionLSCI allows for robust, instant measurement of burns and can easily be applied in a clinical setting. Differences in perfusion during the first week post-burn are related to the outcome after 14 days.
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| 7. |
- Rousseau, Andreas, et al.
(författare)
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Prostaglandins and Radical Oxygen Species Are Involved in Microvascular Effects of Hyperoxia
- 2010
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Ingår i: JOURNAL OF VASCULAR RESEARCH. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 47:5, s. 441-450
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Tidskriftsartikel (refereegranskat)abstract
- Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging. Results were analysed using dose-response modelling. The response to ACh was reduced by 30% during oxygen breathing compared to air breathing [0.98 (0.81-1.15) PU vs. 1.45 (1.30-1.60) PU, p andlt; 0.001]. ED50 values were unchanged [2.25 (1.84-2.75) vs. 2.21 (1.79-2.74), not significant]. Aspirin pre-treatment abolished the difference in response between oxygen breathing and air breathing [maximum: 1.03 (0.90-1.16) vs. 0.89 (0.77-1.01), not significant; ED50: 1.83 (1.46-2.30) vs. 1.95 (1.65-2.30), not significant]. ACh-mediated vasodilatation during 100% oxygen breathing was partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did not change the microvascular response to SNP [1.45 (1.28-1.62) vs. 1.40 (1.26-1.53), not significant]. These results favour the hypothesis that hyperoxic vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical oxygen species may be involved as vitamin C, independently of aspirin, partially restored ACh-mediated vasodilatation during hyperoxia.
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| 8. |
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| 9. |
- Tchou Folkesson, Kim, et al.
(författare)
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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
- 2012
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Ingår i: Microcirculation. - : Informa Healthcare / John Wiley and Sons. - 1073-9688 .- 1549-8719. ; 19:4, s. 352-359
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Tesselaar, Erik, et al.
(författare)
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Assessment of the microvascular effect of insulin using transdermal iontophoresis: optimizing drug delivery in JOURNAL OF VASCULAR RESEARCH, vol 48, Suppl. 1, Poster Session II/2, pp 127-127
- 2011
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Ingår i: JOURNAL OF VASCULAR RESEARCH. - : Karger. - 9783805599016 ; , s. 127-127
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Konferensbidrag (refereegranskat)abstract
- Transdermal delivery by iontophoresis has been used previously to study the vascular effects of insulin in the cutaneous microcirculation. Although a vasodilatory effect of iontophoretically applied insulin has been shown, the observed increases in perfusion, as measured using laser Doppler flowmetry, are modest, possibly since delivered doses are limited due to the electrochemical properties of the molecule, and the relatively low permeability of the skin. Ethanol, urea and depilatory agents have previously been used to enhance transport of substances during iontophoresis. In this pilot study in 8 healthy volunteers, we aimed to investigate the effect of insulin on skin perfusion, as measured by laser-Doppler flowmetry. We tested various strategies that could possibly enhance the delivery of insulin to the skin using iontophoresis, including the use of an insulin analog (insulin aspart), pretreatment of the skin with ethanol and depilatory cream and using 50%/50% mixtures of insulin/ethanol and insulin/urea. Although a slight increase in skin perfusion was found in most subjects with iontophoresis of regular insulin using a single 10-minute current pulse of 0.02 mA (12 mC, N=4), this effect was not significant. Neither of the two pretreatment methods affected this effect. However, when using 9 x 20sec current pulses of 0.2 mA (36 mC, N=4), and when the drugs were mixed with ethanol in a 50%/50% fraction , a 15- to 17-fold increase in perfusion was found for insulin aspart (p=0.04). Iontophoresis of a control substance (50%/50% ethanol/sodium chloride) did not have any effect on skin perfusion (p=0.32). Similarly, iontophoresis of a mixture of urea and insulin aspart yielded a 14-fold increase in perfusion (p=0.03), while a non significant increase in perfusion was found when urea was mixed with regular insulin (p=0.08) and no change at all with sodium chloride (control, p=0.27). These results indicate that iontophoretic transport of insulin may be enhanced by using mixtures of insulin with ethanol or urea, which may facilitate studies that use iontophoresis to study the vascular effects of insulin in the cutaneous microcirculation. Further studies, for instance using microdialysis, are required to directly measure the delivered dose of insulin during iontophoresis under different conditions.
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