Improved White Matter Cerebrovascular Reactivity after Revascularization in Patients with Steno-Occlusive Disease.

BACKGROUND AND PURPOSE: One feature that patients with steno-occlusive cerebrovascular disease have in common is the presence of white matter (WM) lesions on MRI. The purpose of this study was to evaluate the effect of direct surgical revascularization on impaired WM cerebrovascular reactivity in patients with steno-occlusive disease. MATERIALS AND METHODS: We recruited 35 patients with steno-occlusive disease, Moyamoya disease (n = 24), Moyamoya syndrome (n = 3), atherosclerosis (n = 6), vasculitis (n = 1), and idiopathic stenosis (n = 1), who underwent unilateral brain revascularization using a direct superficial temporal artery-to-MCA bypass (19 women; mean age, 45.8 ± 16.5 years). WM cerebrovascular reactivity was measured preoperatively and postoperatively using blood oxygen level-dependent (BOLD) MR imaging during iso-oxic hypercapnic changes in end-tidal carbon dioxide and was expressed as %Δ BOLD MR signal intensity per millimeter end-tidal partial pressure of CO2. RESULTS: WM cerebrovascular reactivity significantly improved after direct unilateral superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass in the revascularized hemisphere in the MCA territory (mean ± SD, -0.0005 ± 0.053 to 0.053 ± 0.046 %BOLD/mm Hg; P < .0001) and in the anterior cerebral artery territory (mean, 0.0015 ± 0.059 to 0.021 ± 0.052 %BOLD/mm Hg; P = .005). There was no difference in WM cerebrovascular reactivity in the ipsilateral posterior cerebral artery territory nor in the vascular territories of the nonrevascularized hemisphere (P < .05). CONCLUSIONS: Cerebral revascularization surgery is an effective treatment for reversing preoperative cerebrovascular reactivity deficits in WM. In addition, direct-STA-MCA bypass may prevent recurrence of preoperative symptoms.

High volatile anaesthetic conservation with a digital in-line vaporizer and a reflector.

BACKGROUND: A volatile anaesthetic (VA) reflector can reduce VA consumption (VAC) at the cost of fine control of its delivery and CO2 accumulation. A digital in-line vaporizer and a second CO2 absorber circumvent both of these limitations. We hypothesized that the combination of a VA reflector with an in-line vaporizer would yield substantial VA conservation, independent of fresh gas flow (FGF) in a circle circuit, and provide fine control of inspired VA concentrations. METHOD: Prospective observational study on six Yorkshire pigs. A secondary anaesthetic circuit consisting of a Y-piece with 2 one-way valves, an in-line vaporizer and a CO2 absorber in the inspiratory limb was connected to the patient's side of the VA reflector. The other side was connected to the Y-piece of a circle anaesthetic circuit. In six pigs, an inspired concentration of sevoflurane of 2.5% was maintained by the in-line vaporizer. We measured VAC at FGF of 1, 4 and 10 l/min. RESULTS: With the secondary circuit, VAC was 55% less than with the circle system alone at FGF 1 l/min, and independent of FGF over the range of 1-10 l/min. Insertion of a CO2 absorber in the secondary circuit reduced Pet CO2 by 1.3-2.0 kpa (10-15 mmHg). CONCLUSION: A secondary circuit with reflector and in-line vaporizer provides highly efficient anaesthetic delivery, independent of FGF. A second CO2 absorber was necessary to scavenge the CO2 reflected by the anaesthetic reflector. This secondary circuit may turn any open circuit ventilator into an anaesthetic delivery unit.

Technology III: in-line vaporizer with reflector.

As the clinical advantages of vapor anesthesia (VA) for sedation of patients in ICU become more apparent, the ergonomics, economy and safety issues need to be better addressed. Here we describe the use of a new commercial digital in-line anesthetic vaporizer that can be attached to the inspiratory limb of a ventilator. If used with a simple, and easily assembled secondary circuit and anesthetic reflector, the circuit remains remote from the patient, the VA consumption approaches a physical minimum, VA level is controlled and monitored, and the tidal volume size is not limited.

Effects of acute controlled changes in end-tidal carbon dioxide on the diameter of the optic nerve sheath: a transorbital ultrasonographic study in healthy volunteers.

Transorbital ultrasonographic measurement of the diameter of the optic nerve sheath is a non-invasive, bed-side examination for detecting raised intracranial pressure. However, the ability of the optic nerve sheath diameter to predict acute changes in intracranial pressures remains unknown. The aim of this study was to examine the dynamic changes of the optic nerve sheath diameter in response to mild fluctuations in cerebral blood volume induced by changes in end-tidal carbon dioxide. We studied 11 healthy volunteers. End-tidal carbon dioxide was controlled by a model-based prospective end-tidal targeting system (RespirAct™). The volunteers' end-tidal carbon dioxide was targeted and maintained for 10 min each at normocapnia (baseline); hypercapnia (6.5 kPa); normocapnia (baseline 1); hypocapnia (3.9 kPa) and on return to normocapnia (baseline 2). A single investigator repeatedly measured the optic nerve sheath diameter for 10 min at each level of carbon dioxide. With hypercapnia, there was a significant increase in optic nerve sheath diameter, with a mean (SD) increase from baseline 4.2 (0.7) mm to 4.8 (0.8) mm; p < 0.001. On return to normocapnia, the optic nerve sheath diameter rapidly reverted back to baseline values. This study confirms dynamic changes in the optic nerve sheath diameter with corresponding changes in carbon dioxide, and their reversibly with normocapnia.

Vascular Dysfunction in Leukoaraiosis.

BACKGROUND AND PURPOSE: The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. MATERIALS AND METHODS: Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). RESULTS: When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). CONCLUSIONS: Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.

Identifying Significant Changes in Cerebrovascular Reactivity to Carbon Dioxide.

BACKGROUND AND PURPOSE: Changes in cerebrovascular reactivity can be used to assess disease progression and response to therapy but require discrimination of pathology from normal test-to-test variability. Such variability is due to variations in methodology, technology, and physiology with time. With uniform test conditions, our aim was to determine the test-to-test variability of cerebrovascular reactivity in healthy subjects and in patients with known cerebrovascular disease. MATERIALS AND METHODS: Cerebrovascular reactivity was the ratio of the blood oxygen level-dependent MR imaging response divided by the change in carbon dioxide stimulus. Two standardized cerebrovascular reactivity tests were conducted at 3T in 15 healthy men (36.7 ± 16.1 years of age) within a 4-month period and were coregistered into standard space to yield voxelwise mean cerebrovascular reactivity interval difference measures, composing a reference interval difference atlas. Cerebrovascular reactivity interval difference maps were prepared for 11 male patients. For each patient, the test-retest difference of each voxel was scored statistically as z-values of the corresponding voxel mean difference in the reference atlas and then color-coded and superimposed on the anatomic images to create cerebrovascular reactivity interval difference z-maps. RESULTS: There were no significant test-to-test differences in cerebrovascular reactivity in either gray or white matter (mean gray matter, P = .431; mean white matter, P = .857; paired t test) in the healthy cohort. The patient cerebrovascular reactivity interval difference z-maps indicated regions where cerebrovascular reactivity increased or decreased and the probability that the changes were significant. CONCLUSIONS: 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.

Organic nitrate chemistry and its implications for nitrogen budgets in an isoprene- and monoterpene-rich atmosphere: constraints from aircraft (SEAC4RS) and ground-based (SOAS) observations in the Southeast US.

Formation of organic nitrates (RONO2) during oxidation of biogenic volatile organic compounds (BVOCs: isoprene, monoterpenes) is a significant loss pathway for atmospheric nitrogen oxide radicals (NOx), but the chemistry of RONO2 formation and degradation remains uncertain. Here we implement a new BVOC oxidation mechanism (including updated isoprene chemistry, new monoterpene chemistry, and particle uptake of RONO2) in the GEOS-Chem global chemical transport model with ∼25 × 25 km2 resolution over North America. We evaluate the model using aircraft (SEAC4RS) and ground-based (SOAS) observations of NOx, BVOCs, and RONO2 from the Southeast US in summer 2013. The updated simulation successfully reproduces the concentrations of individual gas- and particle-phase RONO2 species measured during the campaigns. Gas-phase isoprene nitrates account for 25-50% of observed RONO2 in surface air, and we find that another 10% is contributed by gas-phase monoterpene nitrates. Observations in the free troposphere show an important contribution from long-lived nitrates derived from anthropogenic VOCs. During both campaigns, at least 10% of observed boundary layer RONO2 were in the particle phase. We find that aerosol uptake followed by hydrolysis to HNO3 accounts for 60% of simulated gas-phase RONO2 loss in the boundary layer. Other losses are 20% by photolysis to recycle NOx and 15% by dry deposition. RONO2 production accounts for 20% of the net regional NOx sink in the Southeast US in summer, limited by the spatial segregation between BVOC and NOx emissions. This segregation implies that RONO2 production will remain a minor sink for NOx in the Southeast US in the future even as NOx emissions continue to decline.

Aqueous-phase mechanism for secondary organic aerosol formation from isoprene: application to the Southeast United States and co-benefit of SO2 emission controls.

Isoprene emitted by vegetation is an important precursor of secondary organic aerosol (SOA), but the mechanism and yields are uncertain. Aerosol is prevailingly aqueous under the humid conditions typical of isoprene-emitting regions. Here we develop an aqueous-phase mechanism for isoprene SOA formation coupled to a detailed gas-phase isoprene oxidation scheme. The mechanism is based on aerosol reactive uptake coefficients (γ) for water-soluble isoprene oxidation products, including sensitivity to aerosol acidity and nucleophile concentrations. We apply this mechanism to simulation of aircraft (SEAC4RS) and ground-based (SOAS) observations over the Southeast US in summer 2013 using the GEOS-Chem chemical transport model. Emissions of nitrogen oxides (NOx ≡ NO + NO2) over the Southeast US are such that the peroxy radicals produced from isoprene oxidation (ISOPO2) react significantly with both NO (high-NOx pathway) and HO2 (low-NOx pathway), leading to different suites of isoprene SOA precursors. We find a mean SOA mass yield of 3.3 % from isoprene oxidation, consistent with the observed relationship of total fine organic aerosol (OA) and formaldehyde (a product of isoprene oxidation). Isoprene SOA production is mainly contributed by two immediate gas-phase precursors, isoprene epoxydiols (IEPOX, 58% of isoprene SOA) from the low-NOx pathway and glyoxal (28%) from both low- and high-NOx pathways. This speciation is consistent with observations of IEPOX SOA from SOAS and SEAC4RS. Observations show a strong relationship between IEPOX SOA and sulfate aerosol that we explain as due to the effect of sulfate on aerosol acidity and volume. Isoprene SOA concentrations increase as NOx emissions decrease (favoring the low-NOx pathway for isoprene oxidation), but decrease more strongly as SO2 emissions decrease (due to the effect of sulfate on aerosol acidity and volume). The US EPA projects 2013-2025 decreases in anthropogenic emissions of 34% for NOx (leading to 7% increase in isoprene SOA) and 48% for SO2 (35% decrease in isoprene SOA). Reducing SO2 emissions decreases sulfate and isoprene SOA by a similar magnitude, representing a factor of 2 co-benefit for PM2.5 from SO2 emission controls.

The dynamics of cerebrovascular reactivity shown with transfer function analysis.

Cerebrovascular reactivity (CVR) is often defined as the increase in cerebral blood flow (CBF) produced by an increase in carbon dioxide (CO2) and may be used clinically to assess the health of the cerebrovasculature. When CBF is estimated using blood oxygen level dependent (BOLD) magnetic resonance imaging, CVR values for each voxel can be displayed using a color scale mapped onto the corresponding anatomical scan. While these CVR maps therefore show the distribution of cerebrovascular reactivity, they only provide an estimate of the magnitude of the cerebrovascular response, and do not indicate the time course of the response; whether rapid or slow. Here we describe transfer function analysis (TFA) of the BOLD response to CO2 that provides not only the magnitude of the response (gain) but also the phase and coherence. The phase can be interpreted as indicating the speed of response and so can distinguish areas where the response is slowed. The coherence measures the fidelity with which the response follows the stimulus. The examples of gain, phase and coherence maps obtained from TFA of previously recorded test data from patients and healthy individuals demonstrate that these maps may enhance assessment of cerebrovascular pathophysiology by providing insight into the dynamics of cerebral blood flow control and distribution.

Cerebral hyperperfusion and decreased cerebrovascular reactivity correlate with neurologic disease severity in MELAS.

OBJECTIVE: To study the mechanisms underlying stroke-like episodes (SLEs) in MELAS syndrome. METHODS: We performed a case control study in 3 siblings with MELAS syndrome (m.3243A>G tRNA(Leu(UUR))) with variable % mutant mtDNA in blood (35 to 59%) to evaluate regional cerebral blood flow (CBF) and arterial cerebrovascular reactivity (CVR) compared to age- and sex-matched healthy study controls and a healthy control population. Subjects were studied at 3T MRI using arterial spin labeling (ASL) to measure CBF; CVR was measured as a change in % Blood Oxygen Level Dependent signal (as a surrogate of CBF) to repeated 10 mmHg step increase in arterial partial pressure of CO2 (PaCO2). RESULTS: MELAS siblings had decreased CVR (p ≤ 0.002) and increased CBF (p < 0.0026) compared to controls; changes correlated with disease severity and % mutant mtDNA (inversely for CVR: r = -0.82 frontal, r = -0.91 occipital cortex; directly for CBF: r = +0.85 frontal, not for occipital infarct penumbra). Mean CVR was reduced more in frontal (p < 0.001) versus occipital cortex (p = 0.002); mean CBF was increased more in occipital (p = 0.001) than frontal (p = 0.0026) cortices compared to controls. CBF correlated inversely with CVR (r = -0.99 in frontal; not in occipital infarct penumbra) suggesting that increased frontal resting flows are at the expense of flow reserve. INTERPRETATION: MELAS disease severity and mutation load were inversely correlated with Interictal CVR and directly correlated with frontal CBF. These metrics offer further insight into the cerebrovascular hemodynamics in MELAS syndrome and may serve as noninvasive prognostic markers to stratify risk for SLEs. CLASSIFICATION OF EVIDENCE: Class III.

Non-invasive measurement of cardiac output using an iterative, respiration-based method.

BACKGROUND: Current non-invasive respiratory-based methods of measuring cardiac output [Formula: see text] make doubtful assumptions and encounter significant technical difficulties. We present a new method using an iterative approach [Formula: see text], which overcomes limitations of previous methods. METHODS: Sequential gas delivery (SGD) is used to control alveolar ventilation [Formula: see text] and CO2 elimination [Formula: see text] during a continuous series of iterative tests. Each test consists of four breaths where inspired CO2 [Formula: see text] is controlled; raising end-tidal Pco2 [Formula: see text] by about 1.33 kPa (10 mm Hg) for the first breath, and then maintaining [Formula: see text] constant for the next three breaths. The [Formula: see text] required to maintain [Formula: see text] constant is calculated using the differential Fick equation (DFE), where [Formula: see text] is the only unknown and is arbitrarily assumed for the first iteration. Each subsequent iteration generates measures used for calculating [Formula: see text] by the DFE, refining the assumption of [Formula: see text] for the next test and converging it to the true [Formula: see text] when [Formula: see text] remains constant during the four test breaths. We compared [Formula: see text] with [Formula: see text] measured by bolus pulmonary artery thermodilution [Formula: see text] in seven pigs undergoing liver transplantation. RESULTS: [Formula: see text] implementation and analysis was fully automated, and [Formula: see text] varied from 0.6 to 5.4 litre min(-1) through the experiments. The bias (between [Formula: see text] and [Formula: see text]) was 0.2 litre min(-1) with 95% limit of agreement from -1.1 to 0.7 litre min(-1) and percentage of error of 32%. During acute changes of [Formula: see text], convergence of [Formula: see text] to actual [Formula: see text] required only three subsequent iterations. CONCLUSIONS: [Formula: see text] measurement is capable of providing an automated semi-continuous non-invasive measure of [Formula: see text].

First records of the blue runner Caranx crysos (Perciformes: Carangidae) in Newfoundland waters.

From August to September 2013, c. 21 specimens of the blue runner Caranx crysos were caught by commercial fishermen in two locations off the south coast of Newfoundland, Canada. These samples represent the first records of C. crysos in Newfoundland waters, and a potential northward range expansion of this species in the north-western Atlantic Ocean. They also illustrate the importance of fisher-derived sampling that spans times and locations outside of the limited range targeted by scientific surveys in this region.

Circadian cerebrovascular reactivity to CO2.

Cerebrovascular reactivity (CVR) assesses the ability of the cerebral vasculature to adjust cerebral blood flow in response to changes in arterial carbon dioxide (CO2), and is used as an indicator of cerebrovascular health. A common method of estimating CVR is to measure the increase in blood flow velocity of the middle cerebral artery (MCAv), using trans-cranial Doppler ultrasound, in response to a CO2 stimulus. We used this method to measure the CVR of 10 subjects in the mornings and evenings of two consecutive days. Mean arterial pressure (MAP) was also measured, and CVR was determined solely from tests where MAP remained unchanged in response to CO2. CVR was measured as the slopes of MCAv responses to a ramp CO2 stimulus fitted with linear regression, and significantly increased from evening to morning each day, with no significant day-to-day differences. We concluded that these measurements of CVR exhibited a circadian rhythm, and were repeatable from one day to the next.

A conceptual model for CO2-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI.

Cerebrovascular reactivity (CVR) is the change in cerebral blood flow (CBF) in response to a change in a vasoactive stimulus. Paradoxical reductions in CBF in response to vasodilatory stimulation ('steal') are associated with vascular pathology. However, a pathophysiological interpretation of 'steal' requires a comprehensive conceptual model linking pathology and changes in blood flow. Herein, we extend a simple model explaining steal published in the late 1960s by incorporating concepts of CBF regulation from more recent studies to generate a comprehensive dynamic model. The main elements of the model are: (a) the relationship between changes in CBF and the arterial partial pressure of carbon dioxide (PaCO2) in healthy vascular regions is sigmoidal; (b) vascular regions vasodilate to compensate for decreased perfusion pressure, leading to (c) an encroachment on vasodilatory reserve and, reduced CVR; (d) a vasodilatory stimulus may increase CBF capacity above the flow capacity of major cerebral blood vessels; and (e) this limitation induces competitive intra-cerebral redistribution of flow from territories with low vasodilatory reserve to those with high reserve. We used CVR measurements generated by applying precise, computer-controlled changes in PaCO2 as the vasoactive stimulus, and measured blood oxygen level dependent (BOLD) MRI signals as high resolution surrogates of CBF to test predictions derived from this model. Subjects were 16 healthy adults and 16 patients with known cerebral steno-occlusive diseases. We observed regional sigmoidal PaCO2-BOLD response curves with a range of slopes; graded changes in PaCO2 resulted in redistributions of BOLD signal consistent with the known underlying vascular pathology and predictions of the model. We conclude that this model can be applied to provide a hemodynamic interpretation to BOLD signal changes in response to hypercapnia, and thereby aid in relating CVR maps to pathophysiological conditions.

Measuring cerebrovascular reactivity: what stimulus to use?

Cerebrovascular reactivity is the change in cerebral blood flow in response to a vasodilatory or vasoconstrictive stimulus. Measuring variations of cerebrovascular reactivity between different regions of the brain has the potential to not only advance understanding of how the cerebral vasculature controls the distribution of blood flow but also to detect cerebrovascular pathophysiology. While there are standardized and repeatable methods for estimating the changes in cerebral blood flow in response to a vasoactive stimulus, the same cannot be said for the stimulus itself. Indeed, the wide variety of vasoactive challenges currently employed in these studies impedes comparisons between them. This review therefore critically examines the vasoactive stimuli in current use for their ability to provide a standard repeatable challenge and for the practicality of their implementation. Such challenges include induced reductions in systemic blood pressure, and the administration of vasoactive substances such as acetazolamide and carbon dioxide. We conclude that many of the stimuli in current use do not provide a standard stimulus comparable between individuals and in the same individual over time. We suggest that carbon dioxide is the most suitable vasoactive stimulus. We describe recently developed computer-controlled MRI compatible gas delivery systems which are capable of administering reliable and repeatable vasoactive CO2 stimuli.

Post-operative hypercapnia-induced hyperpnoea accelerates recovery from sevoflurane anaesthesia: a prospective randomised controlled trial.

BACKGROUND: The time to recovery from vapour anaesthesia is shortened by an increase in ventilation while maintaining normocapnia. Hypercapnia during emergence from anaesthesia in spontaneously breathing patients also increases anaesthetic clearance from the brain by increasing cerebral blood flow. We hypothesised that hypercapnia-induced hyperpnoea accelerates emergence from sevoflurane anaesthesia compared to the standard anaesthesia protocol. METHODS: After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups. In the hypercapnic hyperpnoea group, the end-tidal CO2 was adjusted to a range of 6.0-7.3 kPa to maintain a minute ventilation of 10-15 l/min. Recovery indices were compared using unpaired t-tests and ANOVA. RESULTS: Prior to extubation, minute ventilation and end-tidal CO2 in hypercapnic hyperpnoea and control groups were 10.3 ± 1.7 l/min vs. 5.4 ± 1.2 l/min (P < 0.001) and 6.6 ± 0.6 kPa and 5.2 ± 0.5 kPa (P < 0.001), respectively. Compared to control, the study group had shorter time to extubation [4.4 ± 1.3 (SD) vs. 9.8 ± 4.4 min, P < 0.01], BIS recovery to > 75 (2.4 ± 0.9 vs. 6.1 ± 3.1 min, P < 0.01), eye opening (3.9 ± 1.6 vs. 9.8 ± 6.2 min, P < 0.01), eligibility for leaving operating room (5.1 ± 1.2 vs. 11.1 ± 4.6 min, P < 0.01), and post-anaesthesia care unit (73.9 ± 14.2 vs. 89.4 ± 22.6) CONCLUSION: Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room.

Central-peripheral respiratory chemoreflex interaction in humans.

We investigated the interaction between the central and peripheral chemoreflexes in humans using a temporal separation technique in three tests. In two tests hyperventilation was used to reduce central P(CO)2 . In these tests the difference in the responses to the same step increases in P(CO)2 to 45 mmHg at normoxic and hypoxic O(2) tensions provided a measure of the response to isocapnic hypoxia at a low central P(CO)2. In a third test the response to a hypoxic step during sustained isocapnia at 45mmHg provided a measure of the response to isocapnic hypoxia at a high central P(CO)2. The responses to isocapnic hypoxia at high and low central P(CO)2were not significantly different, confirming the conclusion of previous studies that central and peripheral chemoreflex signals interact additively. This finding contrasts with those from recent animal experiments and emphasizes the need for caution when using animal experiments to make conclusions about the physiology of the respiratory chemoreflexes in humans.

Measuring venous blood volume changes during activation using hyperoxia.

This study describes a novel method for measuring relative changes in venous cerebral blood volume (CBVv) using hyperoxia as a contrast agent. This method exploits the extravascular BOLD effect and its dependency on both task-related activation induced changes in venous blood oxygenation and changes due to breathing an oxygen enriched gas mixture. Changes in CBVv on activation can be estimated by comparing the change in transverse relaxation rate, R2*, due to hyperoxia in both baseline and activation states. Furthermore these measurements can be converted into a measure of the percentage change in CBVv. Experiments were performed to measure changes in a CBVv-weighted signal in response to a simple motor task. Both positive and negative changes in CBVv-weighted signal were detected in the positively activated BOLD region.

Respiratory, cerebrovascular and cardiovascular responses to isocapnic hypoxia.

We simultaneously measured respiratory, cerebrovascular and cardiovascular responses to 10-min of isoxic hypoxia at three constant CO(2) tensions in 15 subjects. We observed four response patterns, some novel, for ventilation, middle cerebral artery blood flow velocity, heart rate and mean arterial blood pressure. The occurrence of the response patterns was correlated between some measures. Isoxic hyperoxic and hypoxic ventilatory sensitivities to CO(2) derived from these responses were equivalent to those measured with modified (Duffin) rebreathing tests, but cerebrovascular sensitivities were not. We suggest the different ventilatory response patterns reflect the time course of carotid body afferent activity; in some individuals, carotid body function changes during hypoxia in more complex ways than previously thought. We concluded that isoxic hyperoxic and hypoxic ventilatory sensitivities to CO(2) can be measured using multiple hypoxic ventilatory response tests only if care is taken choosing the isocapnic CO(2) levels used, but a similar approach to measuring the cerebrovascular response to isocapnic hyperoxia and hypoxia is unfeasible.

Increased lung clearance of isoflurane shortens emergence in obesity: a prospective randomized-controlled trial.

BACKGROUND: There is a concern that obesity may play a role in prolonging emergence from fat-soluble inhalational anaesthetics. We hypothesized that increased pulmonary clearance of isoflurane will shorten immediate recovery from anaesthesia and post-anaesthesia care unit (PACU) stay in obese patients. METHODS: After Ethics Review Board approval, 44 ASA I-III patients with BMI>30 kg/m(2) undergoing elective gynaecological or urological surgery were randomized after completion of surgery to either an isocapnic hyperpnoea (IH) or a conventional recovery (C) group. The anaesthesia protocol included propofol, fentanyl, morphine, rocuronium and isoflurane in air/O(2) . Groups were compared using unpaired t-test and ANOVA. RESULTS: Minute ventilation in the IH group before extubation was 22.6 ± 2.7 vs. 6.3 ± 1.8 l/min in the C group. Compared with C, the IH group had a shorter time to extubation (5.4 ± 2.7 vs. 15.8 ± 2.7 min, P<0.01), initiation of spontaneous ventilation (2.7 ± 2.3 vs. 6.5 ± 4.5 min, P<0.01), BIS recovery >75 (3.2 ± 2.3 vs. 8.9 ± 5.8 min, P<0.01), eye opening (4.6 ± 2.9 vs. 13.6 ± 7.1 min, P<0.01) and eligibility for leaving the operating room (7.1 ± 2.9 vs. 19.9 ± 11.9 min, P<0.01). There was no difference in time for eligibility for PACU discharge. CONCLUSION: Increasing alveolar ventilation enhances anaesthetic elimination and accelerates short-term recovery in obese patients.