Non-technical summary Two mechanisms control brain blood flow by changing blood vessel diameter: autoregulation maintains flow in the face of perfusion pressure changes, and brain metabolism adjusts flow to meet metabolic requirements. Brain blood vessel reactivity to CO 2 and O 2 is an important component of the latter. We used a specialised rebreathing technique to change CO 2 over a wide range at constant O 2 , estimating brain blood flow responses from measurements of middle cerebral artery flow velocity. We found that below a threshold CO 2 , blood pressure was unchanged, but blood flow increased in response to CO 2 . This response had a sigmoidal shape, centred at a CO 2 close to resting. Above the threshold, both blood flow and pressure increased with CO 2 . We concluded that this method measures the brain blood flow reactivity to CO 2 without the confounding influence of blood pressure changes. The results obtained contribute to our understanding of brain blood flow regulation.Abstract Carbon dioxide (CO 2 ) increases cerebral blood flow and arterial blood pressure. Cerebral blood flow increases not only due to the vasodilating effect of CO 2 but also because of the increased perfusion pressure after autoregulation is exhausted. Our objective was to measure the responses of both middle cerebral artery velocity (MCAv) and mean arterial blood pressure (MAP) to CO 2 in human subjects using Duffin-type isoxic rebreathing tests. Comparisons of isoxic hyperoxic with isoxic hypoxic tests enabled the effect of oxygen tension to be determined. During rebreathing the MCAv response to CO 2 was sigmoidal below a discernible threshold CO 2 tension, increasing from a hypocapnic minimum to a hypercapnic maximum. In most subjects this threshold corresponded with the CO 2 tension at which MAP began to increase. Above this threshold both MCAv and MAP increased linearly with CO 2 tension. The sigmoidal MCAv response was centred at a CO 2 tension close to normal resting values (overall mean 36 mmHg). While hypoxia increased the hypercapnic maximum percentage increase in MCAv with CO 2 (overall means from 76.5 to 108%) it did not affect other sigmoid parameters. Hypoxia also did not alter the supra-threshold MCAv and MAP responses to CO 2 (overall mean slopes 5.5% mmHg −1 and 2.1 mmHg mmHg −1 , respectively), but did reduce the threshold (overall means from 51.5 to 46.8 mmHg). We concluded that in the MCAv response range below the threshold for the increase of MAP with CO 2 , the MCAv measurement reflects vascular reactivity to CO 2 alone at a constant MAP.

BACKGROUND AND PURPOSE: BOLD MR imaging combined with a technique for precision control of end-tidal pCO 2 was used to produce quantitative maps of CVR in patients with Moyamoya disease. The technique was validated against measures of disease severity by using conventional angiography; it then was used to study the relationship between CVR, vascular steal, and disease severity.

Present methods for measuring red cell volume are based on the dilution of radioactively labelled cells. This precludes the investigation in neonates and pregnant women. We present a simple method for labelling red cells with biotin. These cells may be injected intravenously and subsequently detected using streptavidin-FITC and flow-cytometry. A comparison of the red cell volume estimated using both 51Cr and biotin labelled cells in 19 patients showed no consistent clinically significant difference between the two. This novel label appears to allow red volume to be reliably estimated without using radioactivity.

Accounting for normal test-to-test differences in cerebrovascular reactivity enables the assessment of significant changes in disease status (stability, progression, or regression) in patients with time.

Several clinical conditions [1][2][3] and research protocols [4][5][6][7] require increases in minute ventilation (V 'E) at constant (or nearly constant) arterial carbon dioxide tension (Pa,CO 2 ). At a constant CO 2 production, Pa,CO 2 is inversely related to alveolar ventilation (V 'A), which is a function of V 'E. When V 'E increases, Pa,CO 2 falls unless CO 2 is added to the inspired gas. Maintaining a constant Pa,CO 2 despite an irregular breathing pattern requires continuous and proportional adjustment of the fractional concentration of inspired CO 2 (FI,CO 2 ). Manual adjustments of FI,CO 2 may be adequate if changes in V 'E are slow or if wide variations in V 'A are acceptable. Automated feedback systems provide finer control of V 'A but can result in phase delays, unstable responses or overdamping, despite the use of expensive equipment and complex algorithms. A simple breathing circuit was developed and tested that minimizes the effect of V 'E on V 'A by passively and continuously matching the inspired CO 2 to V 'E regardless of the extent or pattern of breathing. MethodsThe basic concept underlying this approach is that the flow of fresh gas (FI,CO 2 =0) contributing to alveolar CO 2 exchange is kept constant. When V 'E is less than or equal to the fresh gas flow (FGF), the subject inhales only fresh gas. Therefore:When V 'E exceeds FGF, the balance of inhaled gas is drawn from a reservoir containing a reserve gas with a carbon dioxide tension (PCO 2 ) equal to that of mixed venous blood and thus does not participate in CO 2 exchange, ensuring that V 'A is limited by FGF, as indicated by the following equation:where Pv,CO 2 is the oxygenated mixed venous PCO 2 . When the PCO 2 of the mixed venous and reserve gas are not equal, the V 'A depends on both this difference and the difference between V 'E and FGF. Circuit descriptionThe circuit ( fig. 1) A simple, passive circuit that minimizes changes in V 'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO 2 =0%) equal to the subject's minute ventilation (V 'E). During hyperpnoea, the balance of V 'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO 2 ) approximates that of mixed venous blood and therefore contributes minimally to V 'A.Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO 2 (Pet,CO 2 ) at rest, 0, 1.5 and 3.0 min were ( In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea. Eur Respir J 1998; 12: 698-701.

Anaesthesiologists have traditionally been consulted to help design breathing circuits to attain and maintain target end-tidal carbon dioxide (P ET CO 2). The methodology has recently been simplified by breathing circuits that sequentially deliver fresh gas (not containing carbon dioxide (CO 2)) and reserve gas (containing CO 2). Our aim was to determine the roles of fresh gas flow, reserve gas PCO 2 and minute ventilation in the determination of P ET CO 2. We first used a computer model of a non-rebreathing sequential breathing circuit to determine these relationships. We then tested our model by monitoring P ET CO 2 in human volunteers who increased their minute ventilation from resting to five times resting levels. The optimal settings to maintain P ET CO 2 independently of minute ventilation are 1) fresh gas flow equal to minute ventilation minus anatomical deadspace ventilation, and 2) reserve gas PCO 2 equal to alveolar PCO 2. We provide an equation to assist in identifying gas settings to attain a target PCO 2. The ability to precisely attain and maintain a target PCO 2 (isocapnia) using a sequential gas delivery circuit has multiple therapeutic and scientific applications.

White matter hyperintensities are associated with two patterns of altered diffusion characteristics in the surrounding white matter tract network. Diffusion characteristics along white matter tracts improve further away from white matter hyperintensities suggestive of a local penumbra pattern. Also, altered diffusion extends further along tracts traversing white matter hyperintensities suggestive of a Wallerian-type degenerative pattern.

CVR impairment is associated with ADC elevation in normal-appearing WM of patients with severe stenosis or occlusion of the extracranial ICA. This finding is consistent with the presence of early, low-grade ischemic injury.