Evaluation of Cerebrovascular Reactivity in Subjects with and without Obstructive Sleep Apnea.

BACKGROUND: Both obstructive sleep apnea (OSA) and altered cerebrovascular reactivity (CVR) are associated with increased stroke risk. Nevertheless, the incidence of abnormal CVR in patients with OSA is uncertain due to the high variability in the way CVR is measured both within and between studies. We hypothesized that a standardized CVR with a consistent vasoactive stimulus and cerebral blood flow (CBF) measure would be reduced in patients with severe OSA compared with healthy controls. METHODS: This was a prospective study in which subjects with and without OSA were administered a standardized hypercapnic stimulus, and CBF was monitored by blood oxygen level-dependent magnetic resonance signal changes, a high space and time resolved surrogate for CBF. RESULTS: Twenty-four subjects with OSA (mean age 45.9 years, apnea-hypopnea index [AHI] 26.8 per hour) and 6 control subjects (mean age 42.8 years, AHI 2.4 per hour) were included. Compared with controls, subjects with OSA had a significantly greater whole brain (.1565 versus .1094, P = .013), gray matter (.2077 versus .1423, P = .009), and white matter (.1109 versus .0768, P = .024) CVR, respectively. CONCLUSIONS: Contrary to expectations, subjects with OSA had greater CVR compared with control subjects.

CO2 blood oxygen level-dependent MR mapping of cerebrovascular reserve in a clinical population: safety, tolerability, and technical feasibility.

PURPOSE: To evaluate the safety, tolerability, and technical feasibility of mapping cerebrovascular reactivity (CVR) in a clinical population by using a precise prospectively targeted CO(2) stimulus and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging. MATERIALS AND METHODS: A chart review was performed of all CVR studies from institutional review board-approved projects at a tertiary care hospital between January 1, 2006, and December 1, 2010. Informed consent was obtained. Records were searched for the incidence of adverse events and failed examinations. CVR maps were evaluated for diagnostic quality by two blinded observers and were categorized as good, diagnostic but suboptimal, or nondiagnostic. Outcomes were presented as raw data and descriptive statistics (means ± standard deviations). Intraclass correlation coefficient was used to determine interobserver variability. RESULTS: Four hundred thirty-four consecutive CVR examinations from 294 patients (51.8% female patients) were studied. Patient age ranged from 9 to 88 years (mean age, 45.9 years ± 20.6). Transient symptoms, such as shortness of breath, headache, and dizziness, were reported in 48 subjects (11.1% of studies) during hypercapnic phases only. There were no neurologic ischemic events, myocardial infarctions, or other major complications. The success rate in generating CVR maps was 83.9% (364 of 434). Of the 70 (16.1%) failed examinations, 25 (35.7%) were due to discomfort; eight (11.4%), to head motion; two (2.9%), to inability to cooperate; seven (10.0%), to technical difficulties with equipment; and 28 (40.0%), to unknown or unspecified conditions. Among the 364 remaining successful examinations, good quality CVR maps were obtained in 340 (93.4%); diagnostic but suboptimal, in 12 (3.3%); and nondiagnostic, in 12 (3.3%). CONCLUSION: CVR mapping by using a prospectively targeted CO(2) stimulus and BOLD MR imaging is safe, well tolerated, and technically feasible in a clinical patient population.

The interaction of carbon dioxide and hypoxia in the control of cerebral blood flow.

Both hypoxia and carbon dioxide increase cerebral blood flow (CBF), and their effective interaction is currently thought to be additive. Our objective was to test this hypothesis. Eight healthy subjects breathed a series of progressively hypoxic gases at three levels of carbon dioxide. Middle cerebral artery velocity, as an index of CBF; partial pressures of carbon dioxide and oxygen and concentration of oxygen in arterial blood; and mean arterial blood pressure were monitored. The product of middle cerebral artery velocity and arterial concentration of oxygen was used as an index of cerebral oxygen delivery. Two-way repeated measures analyses of variance (rmANOVA) found a significant interaction of carbon dioxide and hypoxia factors for both CBF and cerebral oxygen delivery. Regression models using sigmoidal dependence on carbon dioxide and a rectangular hyperbolic dependence on hypoxia were fitted to the data to illustrate this interaction. We concluded that carbon dioxide and hypoxia act synergistically in their control of CBF so that the delivery of oxygen to the brain is enhanced during hypoxic hypercapnia and, although reduced during normoxic hypocapnia, can be restored to normal levels with progressive hypoxia.

Assessing the effect of unilateral cerebral revascularisation on the vascular reactivity of the non-intervened hemisphere: a retrospective observational study.

OBJECTIVES: Unilateral haemodynamically significant large-vessel intracranial stenosis may be associated with reduced blood-oxygen-level-dependent (BOLD) cerebrovascular reactivity (CVR), an indicator of autoregulatory reserve. Reduced CVR has been associated with ipsilateral cortical thinning and loss in cognitive function. These effects have been shown to be reversible following revascularisation. Our aim was to study the effects of unilateral revascularisation on CVR in the non-intervened hemisphere in bilateral steno-occlusive or Moyamoya disease. STUDY DESIGN: A retrospective observational study. SETTING: A routine follow-up assessment of CVR after a revascularisation procedure at a research teaching hospital in Toronto (Journal wants us to generalise). PARTICIPANTS: Thirteen patients with bilateral Moyamoya disease (age range 18 to 52 years; 3 males), seven patients with steno-occlusive disease (age range 18 to 78 years; six males) and 27 approximately age-matched normal control subjects (age range 19-71 years; 16 males) with no history or findings suggestive of any neurological or systemic disease. INTERVENTION: Participants underwent BOLD CVR MRI using computerised prospective targeting of CO2, before and after unilateral revascularisation (extracranial-intracranial bypass, carotid endarterectomy or encephaloduroarteriosynangiosis). Pre-revascularisation and post-revascularisation CVR was assessed in each major arterial vascular territory of both hemispheres. RESULTS: As expected, surgical revascularisation improved grey matter CVR in the middle cerebral artery (MCA) territory of the intervened hemisphere (0.010±0.023 to 0.143±0.010%BOLD/mm Hg, p<0.01). There was also a significant post-revascularisation improvement in grey matter CVR in the MCA territory of the non-intervened hemisphere (0.101±0.025 to 0.165±0.015%BOLD/mm Hg, p<0.01). CONCLUSIONS: Not only does CVR improve in the hemisphere ipsilateral to a flow restoration procedure, but it also improves in the non-intervened hemisphere. This highlights the potential of CVR mapping for staging and evaluating surgical interventions.

Assessing cerebrovascular reactivity abnormality by comparison to a reference atlas.

Attribution of vascular pathophysiology to reductions in cerebrovascular reactivity (CVR) is confounded by subjective assessment and the normal variation between anatomic regions. This study aimed to develop an objective scoring assessment of abnormality. CVR was measured as the ratio of the blood-oxygen-level-dependent magnetic resonance signal response divided by an increase in CO2, standardized to eliminate variability. A reference normal atlas was generated by coregistering the CVR maps from 46 healthy subjects into a standard space and calculating the mean and standard deviation (s.d.) of CVR for each voxel. Example CVR studies from 10 patients with cerebral vasculopathy were assessed for abnormality, by normalizing each patient's CVR to the same standard space as the atlas, and assigning a z-score to each voxel relative to the mean and s.d. of the corresponding atlas voxel. Z-scores were color coded and superimposed on their anatomic scans to form CVR z-maps. We found the CVR z-maps provided an objective evaluation of abnormality, enhancing our appreciation of the extent and distribution of pathophysiology compared with CVR maps alone. We concluded that CVR z-maps provide an objective, improved form of evaluation for comparisons of voxel-specific CVR between subjects, and across tests sites.

Normal hypercapnic cerebrovascular conductance in obstructive sleep apnea.

Both obstructive sleep apnoea (OSA) and impaired cerebrovascular reactivity (CVR) are associated with an increased risk of stroke. We therefore hypothesized that CVR would be decreased in OSA patients. Since OSA is associated with altered endothelial function and this dysfunction may in turn lead to impaired CVR, we further hypothesized that a CVR decrease could be the responsible mechanism for stroke. Middle cerebral artery blood flow velocity (MCAv) and mean arterial blood pressure (MAP) responses to hypercapnia were measured to determine cerebrovascular conductance (MCAv/MAP). Overnight changes in conductance CVR were assessed in treatment naïve, otherwise healthy OSA (n=13) and non-OSA (n=9) subjects at two isoxic tensions (150 and 50mmHg). We found no significant overnight changes in CVR for either group. There were no differences in CVR between OSA and non-OSA subjects for either isoxic tension, although CVR was increased in hypoxia.

Human skin hypoxia modulates cerebrovascular and autonomic functions.

Because the skin is an oxygen sensor in amphibians and mice, we thought to confirm this function also in humans. The human upright posture, however, introduces additional functional demands for the maintenance of oxygen homeostasis in which cerebral blood flow and autonomic nervous system (ANS) function may also be involved. We examined nine males and three females. While subjects were breathing ambient air, at sea level, we changed gases in a plastic body-bag during two conditions of the experiment such as to induce skin hypoxia (with pure nitrogen) or skin normoxia (with air). The subjects performed a test of hypoxic ventilatory drive during each condition of the experiment. We found no differences in the hypoxic ventilatory drive tests. However, ANS function and cerebral blood flow velocities were modulated by skin hypoxia and the effect was significantly greater on the left than right middle cerebral arteries. We conclude that skin hypoxia modulates ANS function and cerebral blood flow velocities and this might impact life styles and tolerance to ambient hypoxia at altitude. Thus the skin in normal humans, in addition to its numerous other functions, is also an oxygen sensor.

End-inspiratory rebreathing reduces the end-tidal to arterial PCO2 gradient in mechanically ventilated pigs.

PURPOSE: Noninvasive monitoring of the arterial partial pressures of CO(2) (PaCO(2)) of critically ill patients by measuring their end-tidal partial pressures of CO(2) (PETCO(2)) would be of great clinical value. However, the gradient between PETCO(2) and PaCO(2) (PET-aCO(2)) in such patients typically varies over a wide range. A reduction of the PET-aCO(2) gradient can be achieved in spontaneously breathing healthy humans using an end-inspiratory rebreathing technique. We investigated whether this method would be effective in reducing the PET-aCO(2) gradient in a ventilated animal model. METHODS: Six anesthetized pigs were ventilated mechanically. End-tidal gases were systematically adjusted over a wide range of PETCO(2) (30-55 mmHg) and PETO(2) (35-500 mmHg) while employing the end-inspiratory rebreathing technique and measuring the PET-aCO(2) gradient. Duplicate arterial blood samples were taken for blood gas analysis at each set of gas tensions. RESULTS: PETCO(2) and PaCO(2) remained equal within the error of measurement at all gas tension combinations. The mean ± SD PET-aCO(2) gradient (0.13 ± 0.12 mmHg, 95% CI -0.36, 0.10) was the same (p = 0.66) as that between duplicate PaCO(2) measurements at all PETCO(2) and PETO(2) combinations (0.19 ± 0.06, 95% CI -0.32, -0.06). CONCLUSIONS: The end-inspiratory rebreathing technique is capable of reducing the PET-aCO(2) gradient sufficiently to make the noninvasive measurement of PETCO(2) a useful clinical surrogate for PaCO(2) over a wide range of PETCO(2) and PETO(2) combinations in mechanically ventilated pigs. Further studies in the presence of severe ventilation-perfusion (V/Q) mismatching will be required to identify the limitations of the method.