| 1. |
- 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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| 2. |
- Thorfinn, Johan, 1970-
(författare)
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Studies on sitting pressure and buttock microcirculation : aiming at developing an alarm in the prevention of pressure ulcers in patients with spinal cord injuries
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pressure ulcers in patients with spinal cord injuries are a major problem, the prevalence in this group being reported as high as 20 – 30 percent. Most pressure ulcers develop around the pelvic girdle, and the key-contributing factor in the development of pressure ulcers is ischaemia due to longstanding pressure. Loss of mobility and lack of sensation below the level of injury are prominent risk factors for the development of pressure ulcers. Although many factors are known to contribute to pressure ulcer development, the exact aetiology is not completely clear. Prevention is suggested as the best way to deal with the problem. The studies in this thesis investigate some aspects of the physiology of sitting in patients with spinal cord injuries and healthy controls, aiming at developing a pressure ulcer alarm device to aid in the prevention of pressure ulcers. Methods used are laser Doppler perfusion imaging (LDPI) for measurement of superficial skin blood flow, as well microdialysis and a microelectrode (Licox®) to measure direct and indirect signs of ischaemia. In addition sitting pressures are mapped. The main findings are that patients with spinal cord injuries have almost four-fold mean maximum sitting pressures 43 and 49 N/cm2, left and right buttock) compared with healthy controls 12 and 13 N/cm2, left and right buttock). In the subcutaneous fat in healthy individuals, the tissue oxygen pressure decreases significantly during 30 minutes of sitting on a wheel chair cushion 13,7 mmHg) compared with 30 minutes of sitting on a hard surface 19,8 mmHg) implying that the tissues deep in the skin are exposed to a reduction in blood supply. This is also confirmed by a decrease in extracellular glucose during sitting for 30 minutes on a hard surface 1,8 mmol/L) and on a wheel chair cushion 1,7 mmol/L). The post-sitting reactive hyperaemia is dependent on duration of sitting in both patients and healthy subjects. It seems to be attenuated in patients in the sitting position but intensified while lying prone. Furthermore, four repeated loadings on a hard surface 15 minutes of sitting followed by five minutes of rest) without allowing the tissues to return to resting perfusion results in a significantly increasing reactive hyperaemia for each loading in healthy subjects, suggesting that it is important to unload the buttock skin completely before the next sitting period starts. This thesis also describes the construction of an alarm device that measures surface interface pressures during sitting continuously in eight predefined points, to alert the user by an audible signal after a given period of time when the pressure has reached a dangerously high level. It is concluded that the reactive hyperaemia that is observed in the buttock skin after sitting, as well as the reduction in glucose and oxygen in adipose tissue during sitting, are due to a reduction in blood supply relative or absolute ischaemia) caused by a compression of the vasculature by the ischial tuberosities. These findings imply a multilayer aetiology in pressure ulcer development. The altered hyperaemic reaction in patients with spinal cord injuries after sitting is possibly related to alterations in sympathetic activity due to the cord lesion. Lastly, the alarm device is supposed to be an aid to pressure ulcer prevention in patients with spinal cord injuries who lack normal sensory feedback.
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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. |
- Orwelius, Lotti, 1956-
(författare)
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Health related quality of life in adult former intensive care unit patients
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients treated in an intensive care unit (ICU) are seriously ill, have a high co‐morbidity, morbidity and mortality. ICUs are resource – demanding as they consume significant hospital resources for a minority of patients. The development of new medical procedures for critical care patients has over the years led to survival of larger numbers with more complex illnesses and extensive injuries. Improved survival rates lead to needs for outcome measures other than survival. The present study examines health‐related quality of life (HRQoL) and factors assumed to be important for the long term HRQoL for former ICU patients.Methods: This is a multicenter cohort study of 980 adult patients admitted to one of three mixed medical‐surgical ICUs in Southern Sweden, during 2000 to 2004. The patients were studied at four different occasions after their critical illness: 6, 12, 24, and 36 months after discharge from the ICU and hospital. HRQoL was assessed by the EuroQol 5‐Dimensions (EQ‐5D) and Medical Outcome Short Form (SF‐36), sleep disturbances by the Basic Nordic Sleep questionnaire (BNSQ), and pre‐existing diseases was collected by self‐reported disease diagnosis. Data from a large public health survey (n=6093) of the county population were used as reference group.Results: Compared with the age and sex adjusted general reference group the patients who had been in the ICU had significantly lower scores on EQ‐5D and in SF‐ 36 all eight dimensions. This was seen both for the general ICU patients as well as for the multiple trauma patients. Significant improvement over time was seen only in single and separate dimensions for the general ICU group, and for the multiple trauma group. Long term effects of ICU care on sleep patterns were found minor as 70 % reported an unchanged sleep pattern and only 9% reported worse sleep after the IC period. Pre‐existing diseases were found to be the factor that had the largest influence on HRQoL in both the short‐ and long term perspective for the general ICU patients as well as for the multiple trauma patients. It was also found to have negative impact on sleep. IC ‐related factors showed only a minor influence on HRQoL or sleep patterns after the ICU stay.Conclusions: This multicenter study shows that pre‐existing diseases influence the HRQoL short‐ and long‐term after IC, and it must be accounted for when HRQoL and outcome after IC are studied. Approximately, 50% of the decline in HRQoL for the ICU patients could be explained by pre‐existing diseases. Future research needs to focus on the remaining factors of importance for the total HRQoL impairment for these patients.
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