Introduction the Cerebral Circulation Is Regulated to Match Cerebral Blood Flow (cbf) to the Varying Metabol- Ic Needs of the Tissue Perfused, despite Possible Changes in Systemic Arterial Pressure

THE CEREBRAL CIRCULATION IS REGULATED TO MATCH CEREBRAL BLOOD FLOW (CBF) TO THE VARYING METABOLIC NEEDS OF THE TISSUE PERFUSED, DESPITE POSSIBLE CHANGES IN SYSTEMIC ARTERIAL PRESSURE (AP). The CBF is determined by the ratio between cerebral perfusion pressure (CPP) and vascular resistance. The CPP may be computed as the difference between AP and intracranial pressure (ICP) because blood pressure in the collapsible venous vessels upstream of the dural sinuses is assumed to be equal to ICP (ie, the venous cerebrovascular bed is modeled as a Starling resistor).1 The interaction between AP, ICP, and cerebrovascular resistance leads to complex fluctuations in CBF at frequencies lower than the heart rate, as reported in adults2-8 and in newborn babies.9-11 Fluctuations in CBF might be essential to physiologic circulatory function and be generated by regulatory mechanisms. Alternatively, homeostasis might be maintained despite such fluctuations, dampened by regulatory mechanisms. Accordingly, the relationship between spontaneous fluctuations in CBF and those in CPP provides insight into the dynamic properties of cerebral autoregulation in health4,5,7,8,12 and disease.3,6 Slow fluctuations in CPP are followed by autoregulatory changes in cerebrovascular resistance, which cause a phase shift between oscillations in CPP and those in CBF and result in CBF fluctuations apparently preceding CPP fluctuations.7 No such phase advance of CBF before CPP is evident at higher frequencies, which supports the view that cerebral autoregulation behaves as a high-pass filter.3,5,6,12 To our knowledge, there has been no quantitative assessment during sleep of the physiologic relationship between spontaneous fluctuations in CBF and those in CPP, possibly because of the lack of ICP measurements in physiologic conditions. The aim of this study was to provide insight into the impact that the regulation of vascular resistance has on CBF during sleep, by quantifying the extent to which variability in CBF is related to that of CPP in the different states of the wake-sleep cycle. The CBF was measured by an ultrasonic flow probe around the superior sagittal sinus, which yields continuous and quantitative measurements of blood flow.13 The work was performed on newborn lambs, a model widely used to investigate sleep physiology during early postnatal development. The extent to which CPP variability determines variability in CBF during sleep is of substantial importance in newborn life, when both total sleep duration and rapid-eye-movement (REM) sleep duration are at a lifetime maximum.14 Prominent cardiovascular and ventilatory variability is commonly observed in REM sleep15 and reflects the impairment of homeostatic regulation, which has been demonstrated in this state.15,16 In REM sleep, cardiorespiratory disturbances may not be effectively buffered by the developing cardiovascular control system of the newborn,14,17 particularly in pathophysiologic conditions in which protective arousal, circulatory, and respiratory responses may become inef-