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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cigarette smoking during pregnancy increases the incidence of perinatal mortality and Sudden Infant Death Syndrome (SIDS). We have evaluated prenatal or postnatal nicotine exposure in developing rats to examine the potential role of altered neurotransmitter receptor expression in these processes. Pregnant rats received continuous infusions of nicotine throughout gestation, at doses mimicking the plasma levels found in smokers. After birth, cardiac M2-muscarinic cholinergic receptors, which are responsible for inhibitory autonomic actions, were enhanced in the nicotine group, coincidentally with decreases in stimulatory beta-adrenergic receptors that have been demonstrated previously. Studies of adenylyl cyclase activity confirmed that the changes in receptor binding represented functional alterations: the stimulatory response to isoproterenol was obtunded by prenatal nicotine exposure, whereas the inhibitory response to carbachol was enhanced. Elevations of M2-muscarinic receptor binding were not generalized to all tissues, as the same prenatal nicotine treatment elicited a reduction in these receptors in the brainstem, an effect that has also been noted in infants who died of SIDS; we found no effects of prenatal nicotine on brainstem M1-receptor binding. Postnatal administration of nicotine produced similar brainstem receptor effects when treatment was conducted during the first postnatal week but not thereafter; postnatal nicotine treatment did not affect cardiac M2-receptor binding. Thus, during a critical developmental period, nicotine exposure produces cardiac and brainstem receptor imbalances that favor inhibitory responses, effects that can contribute to morbidity and mortality evoked by hypoxic episodes, such as those experienced during parturition, sleep apnea or airway obstruction.
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PMID:Cholinergic receptors in heart and brainstem of rats exposed to nicotine during development: implications for hypoxia tolerance and perinatal mortality. 1006 68

1. Phenothiazine use in infants has been implicated in apparent life-threatening events, sleep apnoea and Sudden Infant Death Syndrome. 2. The aim of this study was to investigate the cumulative effects of a commonly used antihistamine medication containing promethazine on airway protective mechanisms and cardiorespiratory responses in 42 healthy neonatal piglets (21 naturally sleeping, 21 sedated sleeping). 3. Sedated piglets were given 1.5 mg/kg, p.o., promethazine 2 h prior to each recording session. Control animals slept naturally with no sedative given. On three consecutive days in all piglets, physiological recordings were made during sleep; on at least one of these days, simultaneous physiological and radiological observations were made. 4. Following sedation, sleep time and time in active sleep were increased significantly (P < 0.01). The spontaneous occurrence of swallowing, arousal, body movement, gastrooesophageal reflux and apnoea was compared between naturally and sedated sleeping piglets. Sedation with promethazine significantly decreased the spontaneous occurrence of swallowing (P < 0.05) and arousal (P < 0.05) and increased the occurrence of both central (P < 0.05) and obstructive sleep apnoea (P < 0.0001). 5. By the third day, a cumulative effect of promethazine was seen; the rate of swallowing and body movement significantly decreased (P < 0.01). 6. In summary, a low dose of promethazine profoundly altered sleep characteristics, airway protective mechanisms and cardiorespiratory responses in normal healthy sleeping piglets. Continued use of promethazine over several days may attenuate airway protective mechanisms to a potentially life-threatening degree. Our findings support continued caution in the use of promethazine-containing medications for the sedation of infants.
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PMID:Sedation with promethazine profoundly affects spontaneous airway protection in sleeping neonatal piglets. 1056 15

A developmentally immature sleep pattern has been identified in infants with a recent history of an unexplained life-threatening episode of sleep apnoea who are considered at risk for SIDS. In these infants there is a persistence of Sleep Onset REM Periods (SOREMPS) after prolonged wakefulness when compared to controls matched for age, sex, birthweight and race. This sleep characteristic has not been previously reported.
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PMID:A sleep disturbance in high risk for SIDS infants. 1060 80

In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor.
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PMID:Respiration and parturition affected by conditional overexpression of the Ca2+-activated K+ channel subunit, SK3. 1098 76

SIDS is almost invariably sleep-related. Viable syndrome aetiology must be compatible with its many epidemiologically diverse risk factors, each of which directly or indirectly associates with the creation of psychological and/or physiological infant stress, and the subsequent disruption of normal, contented sleep. During essential deep 'rebound' recovery sleep, arousal ability and upper airway muscle tone decrease further to that in normal sleep, with subsequent upper airway obstruction. When stress impact causes sufficient sleep disruption and physiological fatigue, a failure to arouse and so restore sufficient tone to overcome such obstruction results in sudden, unexpected death. SIDS has therefore many causes which share a final lethal mechanical pathway. Evidence is presented for obstructive apnoea during sleep as being the primary syndrome death mode, for sleep disruption, reduced arousal ability, and infant stress in SIDS, and for risk factor association with the creation of this stress. Specific infant vulnerability in the first 6 months of life to stress predominantly related to total dependency on a carer for gratification of need, and to obstructive sleep apnoea due to normal anatomical, physical, and respiratory immaturity, including rapid physiological fatigue, and peaks in sleep and thermal stress vulnerability, are discussed. Further reasons for the limited age period of SIDS, and for reduced neonatal risk, are given. Prone sleeping risk can relate to positional airway obstruction during normal sleep without prior infant stress. Much of SIDS aetiology appears to concern factors related to socio-economic deprivation and subsequent sub-optimal infant care.
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PMID:Infant stress and sleep deprivation as an aetiological basis for the sudden infant death syndrome. 1117 74

Cardiorespiratory decompensation or even death may result from dysfunction of upper airway reflexes during sleep. This could manifest, for example, as a lack of pharyngeal dilation in obstructive sleep apnoea or failure of autoresuscitation by gasping in sudden infant death syndrome. Data obtained from experiments in anaesthetized cats suggest several clinicophysiological applications for upper airway reflexes possessing important pathogenetic and therapeutic potentials. Such reflex effects include: 1. Pharyngeal dilation as additional treatment in obstructive sleep apnoea. 2. Bronchodilation after deep nasal breathing in asthmatic attacks. 3. Oesophageal sphincter relaxation alleviating gastro-oesophageal reflux. 4. Provocation of sniff- and gasp-like aspiration for reversal of central apnoea. 5. Arousal from sleep increasing the general reactivity. 6. Increase in muscle tone underlying behavioural defence reactions. 7. Increase in sympathetic activity contributing to powerful cardiopulmonary-cerebral resuscitation. 8. Adrenergic reaction mediated by catecholamine secretion.
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PMID:Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation. 1121 78

1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway protective mechanisms and cardiorespiratory reflexes following simulated gastro-oesophageal reflux (GER) to different levels in the oesophagus and pharynx. 2. Physiological and radiographic recordings were made in 21 naturally sleeping (controls) and 21 sedated (1.5 mg/kg, p.o., promethazine) piglets. On 3 consecutive days physiological recordings were made in all piglets during active sleep. Gastro-oesophageal reflux was simulated by the injection of boluses of 0.5 mL HCl, pH 2 or 3, or NaCl (0.9%) at 37 degrees C into the pharynx, upper or lower oesophagus. 3. In healthy neonatal piglets, minimal sedation with promethazine, which did not affect behaviour during wakefulness, revealed previously unreported findings during active sleep. 4. The most significant effects were observed following simulated GER to the pharynx, with no effect observed in the lower oesophagus. In sedated piglets, compared with naturally sleeping piglets, there was a significant reduction in swallowing (P < 0.01), delayed radiological clearance of fluid (P < 0.05), a reduction in breathing rate, oxygen saturation and heart rate and an increase in apnoea. 5. These findings are consistent with a low dose of promethazine producing a significant attenuation of airway protective mechanisms and, thus, stimulation of the laryngeal chemoreflex. The results suggest a mechanism for the association observed between promethazine use and the occurrence of ALTE and SIDS. The results support continued caution and suggest the need for greater regulation of promethazine-containing medications in infants.
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PMID:Airway protection following simulated gastro-oesophageal reflux in sedated and sleeping neonatal piglets during active sleep. 1142 20

We compared the breathing characteristics of 40 infants who subsequently died of sudden infant death syndrome (SIDS) with those of 607 healthy infants matched for sex and age. The infants were between 2 and 19 wk old at the time of recording. Compared with the control group, the infants who died of SIDS experienced significantly more frequent episodes of obstructive and mixed sleep apnea. The duration of the apneic episodes did not exceed 15 s. Moreover, the SIDS group had a greater proportion of infants with obstructive and mixed apneic episodes than did the control group. In both groups, the frequency of episodes among male infants with apnea was greater than that among female infants. After the age of 9 wk, the proportion of male infants with episodes of obstructive apnea was greater in the SIDS group than in the control group. The frequency of apneic episodes decreased with age. The rate of decrease was significantly greater in the control subjects than in the SIDS group. This finding was made mainly in male infants. The present study provides further indirect evidence for a slower maturation of respiratory control in some infants who ultimately die of SIDS.
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PMID:Developmental characteristics of apnea in infants who succumb to sudden infant death syndrome. 1170 97

Pediatric sleep physiology begins with development of the sleep/wake cycle, and the origins of active versus quiet sleep. The 24-hour circadian cycle becomes established at 3 to 6 months. Sleep disorders are rationally approached in pediatrics as age-related. Disorders during infancy commonly include mild, usually self-limited conditions such as sleep-onset association disorder, excessive nighttime feedings, and poor limit-setting. These require behavioral management to avoid long-term deleterious sleep habits. In contrast, other sleep disorders are more ominous, including sudden infant death syndrome (SIDS), central congenital hypoventilation syndrome, and sleep apnea. Childhood is generally the golden age of sleep, with brief latency, high efficiency, and easy awakening. Parasomnias, sometimes stage specific, are manifest here. Adolescents have sleep requirements similar to preteens, posing a challenge for them to adapt to school schedules and lifestyles. Narcolepsy, usually diagnosed in adolescence or early adulthood, is a lifelong sleep disorder that has led to the identification of the hypocretin/orexin neurotransmitter system. This will lead to enhanced understanding of what regulates stage rapid eye movement, and to novel therapeutic advances for hypersomnolence.
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PMID:Childhood sleep disorders: diagnostic and therapeutic approaches. 1189 82

Pediatric sleep physiology begins with development of the sleep/wake cycle, and the origins of active versus quiet sleep. The 24-hour circadian cycle becomes established at 3-6 months. Sleep disorders during infancy commonly include mild, usually self-limited conditions such as sleep-onset association disorder, excessive nighttime feedings, and poor limit-setting. These require behavioral management to avoid long-term deleterious sleep habits. In contrast, other sleep disorders are more ominous, including SIDS, central congenital hypoventilation syndrome, and sleep apnea. Childhood is generally considered the golden age of sleep, with brief latency to sleep onset, high efficiency, and easy awakening. Yet parasomnias, psychological factors, and sleep disturbances associated with common disorders such as ADHD disrupt the idealistic notion of childhood being a period of unfettered sleep. Adolescents have sleep requirements similar to adults, posing a challenge for them to adapt to school schedules and increasingly demanding lifestyles. Narcolepsy, usually diagnosed in adolescence or early adulthood, is a lifelong sleep disorder and has led to the identification of the hypocretin/orexin neurotransmitter system. Research advances in the complex interrelationships between developmental neurobiology, sleep disorders and behavior will lead to an enhanced understanding of the pathophysiology of sleep problems and lead to novel therapeutic strategies for sleep disturbances in children.
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PMID:Children, sleep, and behavior: a complex association. 1198 23


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