Summary Summary Maintenance of adequate cerebral blood flow is essential for normal brain function and survival. The brain receives approximately 15% of cardiac output and is responsible for approximately 20% of total body oxygen consumption. Because of the brain’s limited ability to store energy cerebral blood flow needs to be controlled effectively. To adjust cerebral blood flow to an adequate level the diameter of cerebral vessels is changed. Cerebral blood flow (CBF) is dynamically adjusted to changes in the perfusion pressure, the metabolic activity of the brain, humoral factors and autonomic nerve activity. Control of cerebral blood flow to adjust for changes in cerebral perfusion pressure is called cerebral autoregulation. Disease states of the brain may impair or abolish cerebral autoregulation. The exact function of cerebral autoregulation still remains unclear. Three different mechanisms are thought to play a role contributing to cerebral autoregulation: metabolic, myogenic and neurogenic regulation. Being able to reliably estimate parameters of dynamic cerebral autoregulation with sufficient reproducibility by non-invasive means could improve patient diagnostics and management for several conditions. To assess cerebral autoregulation at least recording of blood pressure and a measure for CBF are required. This thesis aims to improve clinical applicability of testing dynamic cerebral autoregulation (dCA). The first aim of this thesis is to evaluate the use of transfer function analysis (TFA) for quantifying dynamic cerebral autoregulation. Secondly our aim is to evaluate clinical application of the developed dCA analysis. In chapter 2 dCA reproducibility, quantified by intraclass correlation coefficient, is evaluated for different methodological approaches of TFA. Analysis compared raw data pre-processing by mean subtraction versus smoothness priors detrending. Furthermore, spectral density estimation by averaging of subsequent time windows versus smoothing the whole recording spectrum. No significant influence of pre-processing and spectral estimation on dCA parameters was found. Therefore, there seems to be no need to prescribe a specific signal-processing regime. Poor reproducibility of gain and phase was found. Based on reproducibility, no preference can be made for morning versus afternoon measurements. Neither for spontaneous versus paced breathing. In chapter 3 is evaluated if, and to what degree dCA was changed after acetazolamide (ACZ) infusion. Using a body weight adjusted ACZ infusion 138
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