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Mary J Morrell

Publications and source records attributed to Mary J Morrell.

16 recordsLinked to original sources
PubMed2006

Neural consequences of sleep disordered breathing: the role of intermittent hypoxia.

Sleep disordered breathing is characterised by periodic breathing, episodes of hypoxia and repeated arousals from sleep; symptoms include excessive daytime sleepiness, impairment of memory, learning and attention. Recent evidence from animal studies suggests that both intermittent hypoxia and sleep fragmentation can independently lead to neuronal defects in the hippocampus and pre frontal cortex; areas known to be closely associated with neural processing of memory and executive function. We have previously shown that sleep disordered breathing is associated with loss of gray matter concentration within the left hippocampus (47). We have now confirmed and extended this finding in 22 right handed, newly diagnosed male patients (mean (sd): age 51.8 (15.4) yrs, apnea/hypopnea index 53.1 (14.0) events/hr, minimum nocturnal oxygen saturation 75 (8.4) %) and 17 controls matched for age and handedness. Voxel-based morphometry, an automated unbiased technique, was used to characterise changes in gray matter concentration. The magnetic resonance images were segmented and grey matter concentration determined voxel by voxel. Analysis of variance was then preformed, adjusted for overall image intensity, with age as a covariant. Additional to the deficit in the left hippocampus, we found more extensive loss of gray matter bilaterally in the parahippocampus. No additional focal lesions were seen in other brain regions. Based on our findings and data from other human and animal studies, we speculate that in patients with sleep disordered breathing intermittent hypoxia is associated with neural deficit, and further that such lesions may lead to cognitive dysfunction.

Adult↗
PubMed2006

Sleep-disordered breathing in a general heart failure population: relationships to neurohumoral activation and subjective symptoms.

The aim of this study was to determine the prevalence of sleep-related breathing disorders (SDB) in a UK general heart failure (HF) population, and assess its impact on neurohumoral markers and symptoms of sleepiness and quality of life. Eighty-four ambulatory patients (72 male, mean (SD) age 68.6 (10) yrs) attending UK HF clinics underwent an overnight recording of respiratory impedance, SaO2 and heart rate using a portable monitor (Nexan). Brain natriuretic peptide (BNP) and urinary catecholamines were measured. Subjective sleepiness and the impairment in quality of life were assessed (Epworth Sleepiness Scale (ESS), SF-36 Health Performance Score). SDB was classified using the Apnoea/Hypopnoea Index (AHI). The prevalence of SDB (AHI > 15 events h(-1)) was 24%, increasing from 15% in mild-to-moderate HF to 39% in severe HF. Patients with SDB had significantly higher levels of BNP and noradrenaline than those without SDB (mean (SD) BNP: 187 (119) versus 73 (98) pg mL(-1), P = 0.02; noradrenaline: 309 (183) versus 225 (148) nmol/24 h, P = 0.05). There was no significant difference in reported sleepiness or in any domain of SF-36, between groups with and without SDB (ESS: 7.8 (4.7) versus 7.5 (3.6), P = 0.87). In summary, in a general HF clinic population, the prevalence of SDB increased with the severity of HF. Patients with SDB had higher activation of a neurohumoral marker and more severe HF. Unlike obstructive sleep apnoea, SDB in HF had little discernible effect on sleepiness or quality of life as measured by standard subjective scales.

Aged↗
PubMed2006

Temazepam at high altitude reduces periodic breathing without impairing next-day performance: a randomized cross-over double-blind study.

The aim of the study was to examine the efficacy and safety of temazepam on nocturnal oxygenation and next-day performance at altitude. A double-blind, randomized, cross-over trial was performed in Thirty-three healthy volunteers. Volunteers took 10 mg of temazepam and placebo in random order on two successive nights soon after arrival at 5000 m, following a 17-day trek from 410 m. Overnight SaO(2) and body movements, and next-day reaction time, maintenance of wakefulness and cognition were assessed. Compared with placebo, temazepam resulted in a reduction in periodic breathing from a median (range) of 16 (0-81.3)% of the night to 9.4 (0-79.6)% (P = 0.016, Wilcoxon's signed-rank test), associated with a small but significant decrease in mean nocturnal SaO(2) from 78 (65-84)% to 76 (64-83)% (P = 0.013). There was no change in sleep latency (P = 0.40) or restlessness (P = 0.30). Temazepam had no adverse effect on next-day reaction time [241 (201-380) ms postplacebo and 242 (204-386) ms post-temazepam], maintenance of wakefulness (seven trekkers failed to maintain 40 min of wakefulness postplacebo, and four post-temazepam), cognition or acute mountain sickness. At high altitude temazepam reduces periodic breathing during sleep without an adverse effect on next-day reaction time, maintenance of wakefulness or cognition. The 2% reduction in mean SaO(2) post-temazepam is likely to be predominantly because of acclimatization, as by chance more trekkers took temazepam on the first night (19 versus 14). We conclude that at high altitude temazepam is effective in reducing periodic breathing, and is safe to use, without any adverse effect upon next-day performance.

Altitude Sickness↗
PubMed2005

The determinants of therapeutic levels of continuous positive airway pressure in elderly sleep apnea patients.

We have examined the role of age on the continuous positive airway pressure (CPAP) levels required to treat two groups of elderly (n=70) and young (n=70) sleep apneic patients, matched for disease severity (apnea/hypopnea index), body mass index and neck circumference. Elderly patients required lower CPAP levels compared to young [mean (sd): 6.9(1.9)cm H(2)O and 9.4(3.5)cm H(2)O, respectively; P<0.0001]. To investigate this finding, we studied the effects of CPAP and its components (inspiratory and expiratory positive airway pressure) on lung volume and upper airway resistance in two groups of elderly [n=9, age 71.7(3.3) years] and young [n=9, age 36.7(4.4)] patients with sleep apnea during wakefulness. CPAP produced a greater decrease in airway resistance (P=0.009) and a greater increase in lung volume (P=0.008) in the elderly compared to young patients. We conclude that both the greater lung inflation and the greater direct splinting of the upper airway contributed to the lower CPAP level required by the elderly. Ageing may be an important determinant of therapeutic CPAP levels in clinical practice, especially in older sleep apneic patients.

Adult↗
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

Ventilation is unstable during drowsiness before sleep onset.

Ventilation is unstable during drowsiness before sleep onset. We have studied the effects of transitory changes in cerebral state during drowsiness on breath duration and lung volume in eight healthy subjects in the absence of changes in airway resistance and fluctuations of ventilation and CO2 tension, characteristic of the onset of non-rapid eye movement sleep. A volume-cycled ventilator in the assist control mode was used to maintain CO2 tension close to that when awake. Changes in cerebral state were determined by the EEG on a breath-by-breath basis and classified as alpha or theta breaths. Breath duration and the pause in gas flow between the end of expiratory airflow and the next breath were computed for two alpha breaths which preceded a theta breath and for the theta breath itself. The group mean (SD) results for this alpha-to-theta transition was associated with a prolongation in breath duration from 5.2 (SD 1.3) to 13.0 s (SD 2.1) and expiratory pause from 0.7 (SD 0.4) to 7.5 s (SD 2.2). Because the changes in arterial CO2 tension (PaCO2) are unknown during the theta breaths, we made in two subjects a continuous record of PaCO2 in the radial artery. PaCO2 remained constant from the alpha breaths through to the expiratory period of the theta breath by which time the duration of breath was already prolonged, representing an immediate and altered ventilatory response to the prevailing PaCO2. In the eight subjects, the CO2 tension awake was 39.6 Torr (SD 2.3) and on assisted ventilation 38.0 Torr (1.4). We conclude that the ventilatory instability recorded in the present experiments is due to the apneic threshold for CO2 being at or just below that when awake.

Alpha Rhythm↗
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

Occlusion of the upper airway does not augment the cardiovascular response to arousal from sleep in humans.

The cardiovascular response to an arousal from sleep at the termination of an obstructive apnea is more than double that to a spontaneous arousal. We investigated the hypothesis that stimulation of respiratory mechanoreceptors, by inspiring against an occluded airway during an arousal from sleep, augments the accompanying cardiovascular response. Arousals (>10 s) from stage 2 sleep were induced by a 1-s auditory tone (85 dB) during a concomitant 1-s inspiratory occlusion (O) and without an occlusion [i.e., control arousal (C)] in 15 healthy men (mean +/- SE: age, 25 +/- 1 yr). Arousals were associated with a significant increase in mean arterial blood pressure (MAP) at 4 s (P < 0.001) and a significant decrease in R-R interval at 3 s (P < 0.001). However, the magnitude of the cardiovascular response was not different during C compared with O (MAP: C, 86 +/- 3 to 104 +/- 3 mmHg; O, 86 +/- 3 to 105 +/- 3 mmHg; P = 0.99. R-R interval: C, 1.12 +/- 0.03 to 0.89 +/- 0.04 s; O, 1.11 +/- 0.02 to 0.87 +/- 0.02 s, P = 0.99). Ventilation significantly increased during arousals under both conditions at the second breath (P < 0.001); this increase was not different between the two conditions (C: 4.40 +/- 0.29 to 6.76 +/- 0.61 l/min, O: 4.35 +/- 0.34 to 7.65 +/- 0.73 l/min; P = 0.31). We conclude that stimulation of the respiratory mechanoreceptors by transient upper airway occlusion is unlikely to interact with the arousal-related autonomic outflow to augment the cardiovascular response in healthy young men.

Acoustic Stimulation↗
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↗
PubMed2004

Apnea and history.

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Famous Persons↗
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↗