Dynamic cerebral autoregulation in CVR testing Introduction Cerebral autoregulation is the control mechanism that compensates for fluctua- tions in cerebral perfusion pressure and keeps the cerebral blood flow relatively constant in correspondence with the metabolic need of the brain 1, 22, 26. The response to vasodilatory stimuli such as CO2 is traditionally used to evaluate and quantify what is called cerebrovascular reactivity (CVR) or vasomotor reactivity. CVR can also be assessed by the administration of acetazolamide (ACZ)4, 27, which reversibly dilates the cerebral arteriolae and therefore increases cerebral blood flow. The exact mechanism by which ACZ increases cerebral blood flow remains unclear 12, 17, 35. Using transcranial Doppler sonography the increase in cerebral blood flow can be shown by determining the cerebral blood flow velocity (CBFV) in the main stem of the middle cerebral artery (MCA). Based on the assumption that the diameter of the MCA main stem is constant and vaso- dilatation only occurs more peripherally, CBFV is proportional to cerebral blood flow. CVR is calculated as the percentage increase in CBFV after the administra- tion of ACZ. So, the test results in a single value quantifying the cerebrovascular reactivity to a pharmacological stimulus. Several methods are developed to test dynamic cerebral autoregulation (dCA) with and without induced blood pressure changes. In the former a sudden step- wise increase in arterial blood pressure (ABP) evokes a cerebral flow response. This response typically is characterized by a few seconds lasting increase fol- lowed within approximately 10 seconds by a relatively slow return to the base level. This response can be interpreted as a kind of step-response and is quanti- fied by the so-called autoregulatory index 34. Another approach to evaluate dCA is based on transfer function analysis of the presumed linear control system with ABP as the input signal and the CBFV in the MCA as the output signal 3, 36. By calculating the auto and cross spectra of and between ABP and CBFV, the transfer function and its gain and phase spectrum are estimated. Furthermore, coherence indicates the strength of the linear relation between ABP and CBFV. The relationship between ACZ-induced CVR and simultaneous dCA has not been studied before. This comparison is clinically relevant since it has been suggested that dCA and CVR might test different properties of the cerebrovascu- lar control system 9, 15, 26, 30. Only a thorough understanding of the relations between the outcome of CVR and simultaneous dCA testing may enable proper interpretation of published data across modalities. As part of a research project into different aspects of lacunar stroke we were able to study simultaneously dCA and CVR in patients with lacunar stroke thought to be due to cerebral small vessel disease 8. The simultaneous investigation of dCA 45
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