Biomedical subjects

Douglas R Corfield

Publications and source records attributed to Douglas R Corfield.

10 recordsLinked to original sources

PubMed2006

Cerebral vascular response to hypercapnia: determination with perfusion MRI at 1.5 and 3.0 Tesla using a pulsed arterial spin labeling technique.

PURPOSE: To compare the quantification of cerebral blood flow (CBF) at 1.5 and 3.0 Tesla, under normo- and hypercapnia, and to determine the cerebral vascular response (CVR) of gray matter (GM) to hypercapnia, a pulsed arterial spin labeling technique was used. Additionally, to improve GM CBF quantification a high-resolution GM-mask was applied. MATERIALS AND METHODS: CBF was determined with the QUIPSS II with thin slice TI1 periodic saturation (Q2TIPS) sequence at 1.5 and 3.0 Tesla in the same group of eight subjects, both under normocapnia and hypercapnia. Absolute GM-CBF maps were calculated using a GM-mask obtained from a high-resolution structural scan by segmentation. The CVR to hypercapnia was derived from the quantitative GM-CBF maps. RESULTS: For both field strengths, the GM-CBF was significantly higher under hypercapnia compared to normocapnia. For both conditions, there was no significant difference of GM-CBF for 1.5 and 3.0 Tesla; the same applies to the CVR, which was 4.3 and 4.5%/mmHg at 1.5 and 3.0 Tesla, respectively. CONCLUSION: The method presented allows for the quantification of CBF and CVR in GM at the common clinical field strengths of 1.5 and 3.0 Tesla and could therefore be a useful tool to study these parameters under physiological and pathophysiological conditions.

Adult↗

PubMed2006

Control of cerebral blood flow during sleep and the effects of hypoxia.

During wakefulness, cerebral blood flow (CBF) is closely coupled to regional cerebral metabolism; however CBF is also strongly modulated by breathing, increasing in response to both hypercapnia and hypoxia. During stage III/IV non-rapid eye (NREM) sleep, cerebral metabolism and CBF decrease whilst the partial pressure of arterial CO2 increases due to a reduction in alveolar ventilation. The reduction in CBF during NREM sleep therefore occurs despite a relative state of hypercapnia. We have used transcranial Doppler ultrasound to determine middle cerebral artery velocity, as an index of CBF, and have determined that NREM sleep is associated with a reduction in the cerebrovascular response to hypercapnia. This reduction in reactivity would, at least in part, allow the observed reductions in CBF in this state. Similarly, we have observed that the CBF response to hypoxia is absent during stage III/IV NREM sleep. Nocturnal hypoxia and hypercapnia are major pathogenic factor associated with cardio-respiratory diseases. These marked changes in cerebrovascular control that occur during sleep suggest that the cerebral circulation may be particularly vulnerable to cardio-respiratory insults during this period.

Blood Circulation Time↗

PubMed2005

Overnight changes in the cerebral vascular response to isocapnic hypoxia and hypercapnia in healthy humans: protection against stroke.

BACKGROUND AND PURPOSE: The reduction in hypercapnic cerebral vascular reactivity that occurs in the morning after sleep is associated with an increased risk of cerebral ischemia and stroke. It is not known if the cerebral vascular response to hypoxia is similarly reduced in the morning, but such a reduction could be considered a further risk factor for cerebral vascular disease. METHODS: To test if the cerebral vascular response to hypoxia is reduced in the morning, the overnight changes in the left middle cerebral artery velocity (MCAV) in response to isocapnic hypoxia (IH) and hypercapnia before and after a normal night sleep were determined in 18 individuals. RESULTS: From evening to morning, hypercapnic cerebral vascular reactivity decreased significantly (evening 2.0+/-0.4, morning 1.3+/-0.2 cm/sec/mm Hg; P<0.05); in contrast, the increase in MCAV in response to IH (-10% SaO2) was unchanged (evening 9.0+/-1.4, morning 8.7+/-2.2%; P>0.05). CONCLUSIONS: Our findings indicate that substantial differences exist in the regulation of the cerebral circulation in response to hypoxia and hypercapnia on waking from sleep. An intact cerebral vascular response to IH, during this time period, could be interpreted as a protective mechanism against cerebral ischemia and stroke; this is of particular relevance to patients with obstructive sleep apnea who arouse from sleep during hypoxia.

Adult↗

PubMed2005

Cerebral blood flow changes associated with fluctuations in alpha and theta rhythm during sleep onset in humans.

Cerebral blood flow (CBF) is typically reduced during stable non-rapid eye movement (non-REM) sleep compared with the waking level. It is not known when in the sleep cycle these changes occur. However, spontaneous fluctuations in alpha and theta rhythm during sleep onset are associated with marked changes in cardio-respiratory control. The aim of this study was to test the hypothesis that changes in CBF would occur during sleep onset and would be related to changes in cortical activity. Middle cerebral artery velocity (MCAV) was measured using transcranial Doppler ultrasound, as an index of CBF, in 10 healthy subjects. Sleep state, ventilation, end tidal carbon dioxide (PET,CO2), arterial oxygen saturation (SaO2), mean arterial blood pressure (MABP) and cardiac R-R interval (RR) were monitored simultaneously. Immediately following the transition from alpha to theta rhythm (the transition from wake to sleep), ventilation decreased by 13.4% and tidal volume (VT) by 12.2% (P<0.01); PET,CO2 increased by 1.9% (P<0.01); respiratory frequency (fR) and SaO2 did not change significantly. MCAV increased by 9.7% (P<0.01); MABP decreased by 3.2% (P<0.01) but RR did not change significantly. Immediately following the transition from theta to alpha rhythm (spontaneous awakening), increased by 13.3% (P<0.01); VT increased by 11.4% (P<0.01); PET,CO2 decreased by 1.9% (P<0.01); MCAV decreased by 11.1% (P<0.01) and MABP decreased by 7.5%; fR, SaO2 and RR did not change significantly. These changes in MCAV during sleep onset cannot be attributed to changes in ventilation or MABP. We speculate that the changes in cerebral vascular tone during sleep onset are mediated neurally, by regulatory mechanisms linked to the changes in cortical state, and that these mechanisms are different from those regulating the longer-term reduction in CBF associated with stable non-REM sleep.

Adult↗

PubMed2004

Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness.

Nocturnal hypoxia is a major pathological factor associated with cardiorespiratory disease. During wakefulness, a decrease in arterial O2 tension results in a decrease in cerebral vascular tone and a consequent increase in cerebral blood flow; however, the cerebral vascular response to hypoxia during sleep is unknown. In the present study, we determined the cerebral vascular reactivity to isocapnic hypoxia during wakefulness and during stage 3/4 non-rapid eye movement (NREM) sleep. In 13 healthy individuals, left middle cerebral artery velocity (MCAV) was measured with the use of transcranial Doppler ultrasound as an index of cerebral blood flow. During wakefulness, in response to isocapnic hypoxia (arterial O2 saturation -10%), the mean (+/-SE) MCAV increased by 12.9 +/- 2.2% (P < 0.001); during NREM sleep, isocapnic hypoxia was associated with a -7.4 +/- 1.6% reduction in MCAV (P <0.001). Mean arterial blood pressure was unaffected by isocapnic hypoxia (P >0.05); R-R interval decreased similarly in response to isocapnic hypoxia during wakefulness (-21.9 +/- 10.4%; P <0.001) and sleep (-20.5 +/- 8.5%; P <0.001). The failure of the cerebral vasculature to react to hypoxia during sleep suggests a major state-dependent vulnerability associated with the control of the cerebral circulation and may contribute to the pathophysiologies of stroke and sleep apnea.

Adult↗

PubMed2003

Cardiovascular response to arousal from sleep under controlled conditions of central and peripheral chemoreceptor stimulation in humans.

The cardiovascular response to an arousal occurring at the termination of an obstructive apnea is almost double that to a spontaneous arousal. We investigated the hypothesis that central plus peripheral chemoreceptor stimulation, induced by hypercapnic hypoxia (HH), augments the cardiovascular response to arousal from sleep. Auditory-induced arousals during normoxia and HH (>10-s duration) were analyzed in 13 healthy men [age 24 +/- 1 (SE) yr]. Subjects breathed on a respiratory circuit that held arterial blood gases constant, despite the increased ventilation associated with arousal. Arousals were associated with a significant increase in mean arterial blood pressure at 5 s (P < 0.001) and with a significant decrease in the R-R interval at 3 s (P < 0.001); however, the magnitude of the changes was not significantly different during normoxia compared with HH (mean arterial blood pressure: normoxia, 91 +/- 4 to 106 +/- 4 mmHg; HH, 91 +/- 4 to 109 +/- 5 mmHg; P = 0.32; R-R interval: normoxia, 1.12 +/- 0.04 to 0.90 +/- 0.05 s; HH, 1.09 +/- 0.05 to 0.82 +/- 0.03 [corrected] s; P = 0.78). Mean ventilation increased significantly at the second breath postarousal for both conditions (P < 0.001), but the increase was not significantly different between the two conditions (normoxia, 5.35 +/- 0.40 to 9.57 +/- 1.69 l/min; HH, 8.57 +/- 0.63 to 11.98 +/- 0.70 l/min; P = 0.71). We conclude that combined central and peripheral chemoreceptor stimulation with the use of HH does not interact with the autonomic outflow associated with arousal from sleep to augment the cardiovascular response.

Acoustic Stimulation↗

PubMed2003

CO2 retention in lung disease; could there be a pre-existing difference in respiratory physiology.

Some patients with lung disease retain CO(2), while others with similar lung function do not. This could be explained if CO(2) retainers had a pre-existing low hypercapnic ventilatory response (HCVR) and, from this, a tendency to retain CO(2). To test if such a phenomenon exists in healthy people, we determined the change in end-tidal P(CO(2)) (deltaPET(CO(2))) produced by the addition of a dead-space (DS), during wakefulness and sleep, and related this to the HCVR measured awake. The group mean (n=14) HCVR slope was 2.2+/-1.1 (S.D.) L min(-1) mmHg(-1). The deltaPET(CO(2)) with the application of DS was 1.6+/-1.6 mmHg awake and 2.6+/-2.2 mmHg asleep. During wakefulness the deltaPET(CO(2)) with DS did not correlate with the HCVR slope. However, during sleep, four subjects had a marked increase in the deltaPET(CO(2)) (3.7, 4.3, 6.2, 8.0 mmHg) and a relatively low HCVR (slope 1.5, 1.7, 1.5, 1.7 L min(-1) mmHg(-1), respectively). We speculate that such individuals, should they develop lung disease, may be predisposed to retain CO(2).

Adult↗

PubMed2003

Hypercapnic cerebral vascular reactivity is decreased, in humans, during sleep compared with wakefulness.

During wakefulness, increases in the partial pressure of arterial CO(2) result in marked rises in cortical blood flow. However, during stage III-IV, non-rapid eye movement (NREM) sleep, and despite a relative state of hypercapnia, cortical blood flow is reduced compared with wakefulness. In the present study, we tested the hypothesis that, in normal subjects, hypercapnic cerebral vascular reactivity is decreased during stage III-IV NREM sleep compared with wakefulness. A 2-MHz pulsed Doppler ultrasound system was used to measure the left middle cerebral artery velocity (MCAV; cm/s) in 12 healthy individuals while awake and during stage III-IV NREM sleep. The end-tidal Pco(2) (Pet(CO(2))) was elevated during the awake and sleep states by regulating the inspired CO(2) load. The cerebral vascular reactivity to CO(2) was calculated from the relationship between Pet(CO(2)) and MCAV by using linear regression. From wakefulness to sleep, the Pet(CO(2)) increased by 3.4 Torr (P < 0.001) and the MCAV fell by 11.7% (P < 0.001). A marked decrease in cerebral vascular reactivity was noted in all subjects, with an average fall of 70.1% (P = 0.001). This decrease in hypercapnic cerebral vascular reactivity may, at least in part, explain the stage III-IV NREM sleep-related reduction in cortical blood flow.

Adult↗

PubMed2003

Changes in brain morphology associated with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) causes hypoxemia and fragmented sleep, which lead to neurocognitive deficits. We hypothesised that focal loss of cortical gray matter generally within areas associated with memory processing and learning and specifically within the hippocampus would occur in OSA. METHODS: Voxel-based morphometry, an automated processing technique for magnetic resonance images, was used to characterise structural changes in gray matter in seven right handed, male patients with newly diagnosed OSA and seven non-apneic, male controls matched for handedness and age. RESULTS: The analysis revealed a significantly lower gray matter concentration within the left hippocampus (p=0.004) in the apneic patients. No further significant focal gray matter differences were seen in the right hippocampus and in other brain regions. There was no difference in total gray matter volume between apneics and controls. CONCLUSION: This preliminary report indicates changes in brain morphology in OSA, in the hippocampus, a key area for cognitive processing.

Brain↗

PubMed2002

BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air hunger.

Air hunger (uncomfortable urge to breathe) is a component of dyspnea (shortness of breath). Three human H(2)(15)O positron emission tomography (PET) studies have identified activation of phylogenetically ancient structures in limbic and paralimbic regions during dyspnea. Other studies have shown activation of these structures during other sensations that alert the organism to urgent homeostatic imbalance: pain, thirst, and hunger for food. We employed blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine activation during air hunger. fMRI conferred several advantages over PET: enhanced signal-to-noise, greater spatial resolution, and lack of ionizing radiation, enabling a greater number of trials in each subject. Six healthy men and women were mechanically ventilated at 12-14 breaths/min. The primary experiment was conducted at mean end-tidal PCO(2) of 41 Torr. Moderate to severe air hunger was evoked during 42-s epochs of lower tidal volume (mean = 0.75 L). Subjects described the sensation as "like breath-hold," "urge to breathe," and "starved for air." In the baseline condition, air hunger was consistently relieved by epochs of higher tidal volume (mean = 1.47 L). A control experiment in the same subjects under a background of mild hypocapnia (mean end-tidal PCO(2) = 33 Torr) employed similar tidal volumes but did not evoke air hunger, controlling for stimulus variables not related to dyspnea. During each experiment, we maintained constant end-tidal PCO(2) and PO(2) to avoid systematic changes in global cerebral blood flow. Whole-brain images were acquired every 5 s (T2*, 56 slices, voxel resolution 3 x 3 x 3 mm). Activations associated with air hunger were determined using voxel-based interaction analysis of covariance that compared data between primary and control experiments (SPM99). We detected activations not seen in the earlier PET study using a similar air hunger stimulus (Banzett et al. 2000). Limbic and paralimbic loci activated in the present study were within anterior insula (seen in all 3 published studies of dyspnea), anterior cingulate, operculum, cerebellum, amygdala, thalamus, and basal ganglia. Elements of frontoparietal attentional networks were also identified. The consistency of anterior insular activation across subjects in this study and across published studies suggests that the insula is essential to dyspnea perception, although present data suggest that the insula acts in concert with a larger neural network.

Adult↗