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- Högstedt, Alexandra, 1993-
(författare)
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Microvascular effects of insulin in the skin
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The microcirculation in the skin is essential for skin homeostasis. In instances of altered microvascular function, that may be the result of insulin resistance, tissue morbidity may ensue. The underlying mechanisms are however complex and not fully understood. By studying the physiological effects of insulin in the skin, the understanding of the complex interplay between glucose metabolism and skin microcirculation can be improved. The general aim of this thesis was to develop an experimental in vivo model to study metabolic and microvascular responses to insulin in the skin in healthy subjects. Microdialysis is a suiting technique as it allows for both local delivery of drugs and simultaneous monitoring of the local metabolic and vascular effects in the very same tissue compartment. The effects of local and systemic insulin provocation on skin blood flow and metabolism were investigated using microdialysis urea clearance and laser speckle contrast imaging (paper I). An insulin dependent increase in skin blood flow was observed, presumably induced through the nitric oxide pathway (paper II). Investigating the protein expression during an oral glucose provocation using proteomic approaches however indicates interactions with other pathways, such as the renin-angiotensin system and the kallikrein-kinin system (paper IV). Paper III also investigated methodological concerns regarding the sampling of insulin using microdialysis. This in vivo model can, in the future, be applied to assess the microvascular effects of insulin in the skin in different patient groups, including those with micro-vascular dysfunction due to, for instance, insulin resistance.
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| 2. |
- Zötterman, Johan, 1975-
(författare)
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Laser Speckle Contrast Imaging in Reconstructive Surgery
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesReconstructive surgery aims to restore function or normal appearance by reconstructing defective organs after trauma or disease. In patients undergoing reconstructive surgery, previous trauma, surgery or radiotherapy can result in compromised blood supply. This will affect the viability of the tissue and increases the risk for postoperative complications, such as ischemia and infection. It is therefore important to assess the tissue viability, both before, during and after the surgery. This can be done using different techniques that monitor the perfusion of the skin covering the affected area. In this thesis, LSCI have been evaluated for tissue monitoring in reconstructive surgery. The technique allows for a fast and noninvasive assessment of superficial tissue perfusion over a wide field. Based on previous work on the technology, we have seen clear advantages with LSCI compared to other methods, for example laser Doppler flowmetry (LDF). We have evaluated laser speckle contrast imaging (LSCI) as a tool for tissue monitoring in reconstructive surgery in four studies.MethodsIn study I we used a bench top model and healthy subjects to address methodological concerns subjected to the LSCI technology. We investigated the effect of motion distance and angle on the assessed perfusion value In study II we used a porcine model to compare LSCI and LDF as tools to detect partial and full venous outflow obstruction. We used both methods to assess a flap based on the cranial gluteal artery perforator with partial and complete occlusion of the vein and artery. In study III we used the same porcine model as in study II to investigate the possibility to use LSCI intraoperatively to identify flap areas with compromised circulation and thereby predict areas with a high risk of postoperative necrosis. In study IV we used LSCI for intraoperative evaluation of tissue viability during deep inferior epigastric perforator (DIEP) free flap surgery and to investigate the perfusion distribution according to the Hartrampf zones, as measured with LSCI, in relation to the selected perforator in the deep inferior epigastric perforator free flap.ResultsIn study I we saw that tissue perfusion as measured with LSCI increases with increasing tissue motion, independent of frame rate, number of images, and tissue perfusion. Measured perfusion will decrease when images are acquired at an angle larger than 45° but distances between 15 and 40 cm do not affect the measured perfusion. In study II we observed significant decreases in perfusion during both partial and complete venous occlusion with both LSCI and LDF. However, higher variability seen with LDF, measured as % coefficient of variation. In study III a decrease in perfusion during the first 30 min after raising the flap and a perfusion value below 25 PU after 30 min was a predictor for tissue morbidity 72h after surgery. In study IV the highest perfusion values were found in zone I and higher perfusion in zone II compared to zone III, directly after the flap was raised. No remaining significant difference between zone I, II and III could be seen after anastomosis of the vessels. All flaps with a minimum perfusion <30 PU, measured after the flap was shaped and inserted, later suffered from partial flap necrosis.ConclusionLSCI is a technology that has the potential to contribute to tissue monitoring in reconstructive surgery. It has many advantages over other techniques, such as the fast acquisition time, the spatial resolution and the fact that it is completely non-invasive. However, the current system is still too bulky to be easily introduced into a clinical setting and the technology is also subject to certain drawbacks which limit its usability. It is sensitive to motion artefacts; only superficial tissue is assessed and cannot offer absolute perfusion data. If these disadvantages could be addressed, LSCI could contribute to a more accurate survey of tissue perfusion and thus better outcome in reconstructive surgery.
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| 3. |
- Elawa, Sherif, 1988-
(författare)
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Microvascular Function Assessment after Mastectomy and Radiation Therapy in Breast Cancer Patients : From Methodology to Clinical Application
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Post-mastectomy radiotherapy (PMRT) is an important part of the treatment of breast cancer. It reduces the risk of recurrence and improves overall survival. Scaring and fibrotization of the skin and subcutaneous tissue of the chest wall or remaining breast are among its side-effects. These late side-effects of PMRT may in turn affect skin microcirculation and oxygenation, although this connection is not completely established. In patients that later require breast reconstruction, it is difficult as a plastic surgeon to evaluate if the microcirculatory changes have been affected by PMRT, and how such effects should have an impact on the choice of reconstructive method. In the work presented in this thesis, laser speckle contrast imaging (LSCI), laser-doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) have been used with a strong vasodilator, methyl nicotinate (MN) to study the microcirculatory changes after PMRT.In studies I and II, we aimed to find the optimal concentration of MN and its main mechanisms of action. In healthy volunteers, the microvascular response to different concentrations of MN was evaluated on the forearm using LSCI. It was found that a concentration of 20 mmol/l resulted in a quick vasodilatory response with a long plateau phase, minimal tissue edema and no non-responders. In study II, we utilized locally administered drugs to block the three main pathways responsible for skin vasodilation. Subsequently, we provoked the skin with MN and assessed its effect with LSCI. From this study we could conclude that MN’s mechanism of action is largely mediated by prostaglandins and partly by local sensory nerves.In study III, we examined the skin microcirculatory response in breast cancer patients before, immediately after, and at two and six months following unilateral PMRT, using the contralateral breast as a control. A significant increase in basal skin perfusion and perfusion after application of MN was observed on the irradiated chest wall immediately after RT compared to the contralateral breast and compared to before RT. At six months after RT, there was no longer a difference in basal skin perfusion or after application of MN in the irradiated chest wall compared to the contralateral breast and compared to before RT was given. The results from this study concluded that skin perfusion in the irradiated chest wall had returned to normal when measured six months after RT.In study IV, the late effects on skin microvascular function were studied in women who had undergone mastectomy and PMRT several years prior to the study. Skin perfusion and oxygen saturation was measured with white light diffuse reflectance spectroscopy (DRS) combined with Laser Doppler Flowmetry (LDF) before and after application of MN on the irradiated chest wall with the contralateral non-irradiated breast as control. In this study we found that skin perfusion and oxygenation in the breast are affected several years after radiotherapy and that our method could be a valuable clinical tool prior to deciding surgical procedures after PMRT.To conclude, MN can be topically applied to the skin to reliably assess microvascular function and the microvascular capacity. LSCI and LDF have different strengths and drawbacks, with LSCI having the advantage of having a large spatial resolution that allows for measurements of control areas in the same field of view as the provoked areas. LDF in combination with DRS enabled us to further assess perfusion and oxygenation simultaneously which could be an advantage in fibrotic skin where skin perfusion and oxygen saturation may not correlate with each other. Although the study groups differed between the study examining the early effects of PMRT with the late effects of PMRT, we have been able to non-invasively visualize changes in microcirculation in relation to the acute and chronic phase after PMRT. Future studies are needed to investigate the value of pre-operative measurements with MN provocation for predicting surgical outcome.
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