| 1. |
- Bergkvist, Max, et al.
(författare)
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Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin
- 2020
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Ingår i: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 130
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. Materials and methods: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (C-RBC,(TiVi)), oxygenation (Delta C-OH,(TiVi)) and deoxygenation (Delta C-DOH,(TiVi)) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). Results: During arterial occlusion, C-RBC,(TiVi) remained unchanged while Delta C-OH,(TiVi) decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, C-RBC,C-TiVi increased to 39.2 (18.8) AU (p < 0.001), Delta C-OH,C-TiVi increased to 38.5. During venous occlusion, C-RBC,C-TiVi increased to 28.9 (11.2) AU (p < 0.001), Delta C-OH,C-TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. Conclusion: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.
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| 2. |
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| 3. |
- Droog Tesselaar, Erik, 1977-
(författare)
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Assessment of microvascular function by use of transdermal iontophoresis : methodological aspects
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Assessment of the microcirculation is of major importance in understanding the physiology of the vasculature and in assessing te vascular effects of pathological conditions such as diabetes, hypertension and sepsis. Transdermal iontophoresis can be used to non‐invasively introduce vasoactive drugs into the skin. The response to these drugs of the local cutaneous microvasculature can be measured by laser Doppler flowmetry methods. Although these techniques have been used together for over two decades, there are still important methodological issues to be resolved. This work is aimed at optimizing transdermal iontophoresis as a tool for microvascular assessment by focusing on the main methdological issues: non‐specific vasodilatation, drug delivery protocols and analysis of blood flow data.Non‐specific vasodilatation, an increase blood flow during iontophoresis of non‐vasoactive compounds, is an important problem as it interferes with the response to the administered drug. By investigating this effect in healthy volunteers, we found that the extent of the non‐specific response differs between the positive and negative electrode and that it is dependent on the voltage over the skin andon the ionic strength of the vehicle in which the drug is dissolved. We also found that the extent of the non‐specific response could be reduced by applying local anesthetics and by pre‐treatment with antihistamine drugs. These results suggest that non‐specific effects could be mediated by depolarization or hyperpolarisation of cells, triggering neural and histamine related mechanisms that finally lead to vasodilatation of the local microvasculature.To prevent non‐specific effects from occurring during the experiments, our results show that the current strength and the total electric charge during iontophoresis should be limited to 0.02 mA and12 mC, respectively. Furthermore, drug solutions at physiological ionic strengths should be used. Under these conditions, adequate responses to the most commonly used drugs, acetylcholine (ACh) and sodium nitroprusside (SNP), are obtained while no significant non‐specific vasodilatation occurs.The results of our investigations show that blood responses to ACh and SNP applied by a single iontophoretic pulse can well be escribed by conventional dose‐response models, which enables a more powerful analysis and comparison between drugs or possibly patient groups as compared with conventional aalysis methods. Finally, we have incorporated drug transport and physiological response to the local drug concentration during iontophoresis of vasoactve drugs into a single model. Validation of this model using measured responses to ACh and SNP shows that the commonly used assumption that the local drug concentration during iontophoresis is linearly proportional to the electric charge may not be valid.
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| 4. |
- Droog Tesselaar, Erik, 1977-, et al.
(författare)
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Changes in skin microcirculation during radiation therapy for breast cancer
- 2017
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Ingår i: Acta Oncologica. - Oxfordshire : Taylor & Francis. - 0284-186X .- 1651-226X. ; 56:8, s. 1072-1080
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.MATERIAL AND METHODS: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.RESULTS: In the treated breast, perfusion and RBC concentration were increased after 1-5 fractions (2.66-13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.CONCLUSION: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.
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| 5. |
- Elawa, Sherif, et al.
(författare)
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Microcirculatory changes in the skin after postmastectomy radiotherapy in women with breast cancer
- 2024
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Postmastectomy radiotherapy (PMRT) increases the risk for complications after breast reconstruction. The pathophysiological mechanism underlying this increased risk is not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion in the skin directly after, and at 2 and 6 months after PMRT and to assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate-MN) after PMRT. Skin microvascular responses after PMRT were measured on two sites in the irradiated chest wall of 22 women before, immediately after, and at 2 and 6 months after unilateral PMRT with the contralateral breast as a control. A significant increase in basal skin perfusion was observed in the irradiated chest wall immediately after RT (p < 0.0001). At 2 and 6 months after RT, there was no longer a difference in basal skin perfusion compared to the contralateral breast and compared to baseline. Similarly, the blood flow response in the skin after application of MN was stronger immediately after RT compared to before RT (p < 0.0001), but there was no difference at later time points. These results indicate that the increased risk for complications after surgical procedures are not directly related to changes in skin perfusion and microvascular responsiveness observed after postmastectomy RT.
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| 6. |
- Elawa, Sherif, et al.
(författare)
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Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients
- 2024
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Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 75
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Tidskriftsartikel (refereegranskat)abstract
- The pathophysiological mechanism behind complications associated with postmastectomy radiotherapy (PMRT) and subsequent implant-based breast reconstruction are not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion and saturation in the skin after mastectomy and assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate - MN). Skin microvascular perfusion and oxygenation >2 years after PMRT were measured using white light diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) in the irradiated chest wall of 31 women with the contralateral breast as a control. In the non-irradiated breast, the perfusion after application of MN (median 0.84, 25th-75th centile 0.59-1.02 % RBC × mm/s) was higher compared to the irradiated chest wall (median 0.51, 25th-75th centile 0.21-0.68 % RBC × mm/s, p < 0.001). The same phenomenon was noted for saturation (median 91 %, 25th-75th centile 89-94 % compared to 89 % 25th-75th centile 77-93 %, p = 0.001). Eight of the women (26%) had a ≥10 % difference in skin oxygenation between the non-irradiated breast and the irradiated chest wall. These results indicate that late microvascular changes caused by radiotherapy of the chest wall significantly affect skin perfusion and oxygenation.
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| 7. |
- Henricson, Joakim, 1977-
(författare)
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Assessment of microvascular effects of vasoactive drugs : Methodological in vivo studies in humansbased on iontophoresis
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease is the leading cause of death in western societies and endothelial dysfunction is one of the earliest signs seen in the development of such conditions. Thedevelopment of prognostic tools to aid in the prediction of micro- and macrovascular diseasebased on assessment of vascular reactivity is therefore of paramount importance.Transdermal iontophoresis offers a quick, non-invasive and relatively straightforward way todeliver vasoactive substances in order to provoke a vascular response in man. When combined with either laser Doppler flowmetry (LDF) or tissue viability imaging (TiVi) for quantification of these responses the methodology offers a potentially powerful tool forvascular investigations. The technique has, however, not been established in clinical practice yet and is mostly used in experimental settings. The lack of consensus in what data analysistechnique to use, uncertainty concerning the actual drug dose applied, and the difficulties associated with the assessment of responses to vasoconstrictors may have contributed to thisfact. The aim of this thesis is therefore to address these issues and thus facilitate the use and improve the applicability of transdermal iontophoresis for assessment of cutaneous microvascular function.More specifically, a non-linear dose-response model (Emax-model) that is commonly used in in vitro investigations of vascular function was applied to the iontophoresis data. The resultsshow that the Emax-model accurately describes the cutaneous vascular responses totransdermally iontophoresed acetylcholine (ACh) and, sodium nitroprusside (SNP). The Emaxmodelgenerates variables that can be used for quantitative statistical analysis of data andenables a more powerful analysis compared to the methods presently used. It is furtherdemonstrated that the maximal dose effect and vascular responses vary between differentprotocols with the same total iontophoretic charge but with different current strengths anddurations. This finding implies that the assumption that the local drug dose is linearlyproportional to the iontophoretic charge (used for estimation of delivered drug dose to themicrovascular bed) may be inaccurate in in vivo investigations and that there is need for amore refined model.It is also demonstrated that in a vasoconstrictive setting (iontophoresis of noradrenaline andphenylephrine) TiVi is the favourable technique for measuring vascular responses as it issensitive enough to generate data that can be fitted to the Emax-model even without predilatationof the vessels.
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| 8. |
- Henricson, Joakim, 1977-, et al.
(författare)
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Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Laser-Doppler flowmetry (LDF) is an attractive method to assess blood flow responses butlacks sensitivity to accurately measure low perfusion values during iontophoresis of vasoconstricting drugs without predilatation of the microvascular bed. The aim of this study was to develop a protocol for iontophoresis of noradrenaline (NA) andphenylephrine (Phe) in the skin, using local heating to predilate the microvascular bed andLDF to measure blood flow responses. Three protocols with the same electrical charge (12mC) but different durations and current strengths (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x0.04 mA) were used to study the effect of pulse duration and current strength on the responses. Skin perfusion decreased to 68-78% of the predilatated state with both NA and Phe. Doseresponse plateaus were not obtained with any protocol. The extent of the vasoconstriction depended on the protocol used. These results suggest that predilatation by local heating appears less suitable duringiontophoresis of NA and Phe, due to limited vascular responses and especially absence of response plateaus, even at high current strengths. The latter leads to difficulties in performing proper dose response analyses. Another interesting finding was that the actual dose of NA and Phe given to the tissue was affected not only by the size of the electrical charge, but local blood flow as well.
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| 9. |
- Högstedt, Alexandra, et al.
(författare)
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Effect of N-G-monomethyl l-arginine on microvascular blood flow and glucose metabolism after an oral glucose load
- 2020
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Ingår i: Microcirculation. - : WILEY. - 1073-9688 .- 1549-8719. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor N-G-monomethyl l-arginine using microdialysis. Methods Microdialysis catheters, perfused with N-G-monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. Results After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the N-G-monomethyl l-arginine catheter compared to the control catheter (urea clearance: P amp;lt; .006, glucose dialysate concentration: P amp;lt; .035). No significant effect of N-G-monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). Conclusion Local delivery of N-G-monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.
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