Influence of repeated upper airway obstruction on the arousal and cardiopulmonary response to upper airway obstruction in lambs

Experiments were done on five lambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted.     

Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs

Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to upper airway obstruction during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial Hb oxygen saturation. A tracheotomy was done and a fenestrated tracheotomy tube placed in the trachea. During the study, a 5 F balloon-tipped catheter was inserted into the tracheotomy tube so that air flow could be obstructed by inflating the balloon. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of upper airway obstruction. Carotid denervation significantly affected the arousal response to upper airway obstruction. Arousal occurred during 14 of 14 epochs in quiet sleep and during 12 of 13 epochs in active sleep before the arterial Hb oxygen saturation decreased to 30%. However, the time to arousal was increased and the arterial Hb oxygen saturation at arousal was decreased in carotid-denervated lambs compared with what we have previously observed in carotid-intact lambs. These data provide evidence that the carotid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during upper airway obstruction in lambs. Our results may have implications for sudden infant death syndrome, because it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death.     

Arousal from sleep during rapidly developing hypoxemia in lambs

Arousal is an important protective response that may prevent severe hypoxemia and death during sleep. However, very little is known about arousal from sleep in response to respiratory stimuli in newborns. Experiments were therefore done to investigate the arousal response from sleep to rapidly developing hypoxemia in eight lambs. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial hemoglobin oxygen saturation. A tracheotomy was done and a tracheostomy tube placed in the trachea so that the fraction of inspired oxygen could be changed quickly. No sooner than 3 days after surgery, measurements were made in quiet sleep and active sleep (AS) during 30-s control periods when the animals were breathing 21% oxygen and during experimental periods of hypoxemia when the animals were breathing either 10, 5, or 0% oxygen in nitrogen. During quiet sleep, arousal occurred at similar arterial hemoglobin oxygen saturations (81 +/- 6% on 10% O2, 80 +/- 5% on 5% O2 and 83 +/- 5% on 0% O2) suggesting that arousal was independent of the rate of change of arterial oxygen. However, during AS arousal occurred at different arterial hemoglobin oxygen saturations (76 +/- 6% on 10% O2, 55 +/- 11% on 5% O2, and 44 +/- 17% on 0% O2) suggesting that arousal was dependent on the rate of change of arterial oxygen. During some epochs of AS, electrocortical signs of cerebral hypoxia and primary apnea occurred before arousal. These data provide evidence that arousal from quiet sleep in response to hypoxemia occurs once an arousal threshold has been reached.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naloxone does not alter the arousal response decrement after repeated exposure to hypoxemia during sleep in lambs.

Experiments were done to determine if endogenous opiates cause the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs. Five lambs were anesthetized and instrumented for sleep staging and measurement of arterial Hb oxygen saturation. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing 5% oxygen. The experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen, once the lamb aroused from sleep. After each lamb had been exposed to 5% oxygen during 100 consecutive epochs of sleep, naloxone--an opiate antagonist--was given i.v. in a dose of 3 mg/kg as a bolus. The animals continued to be exposed to 5% oxygen during six more epochs of sleep after the administration of naloxone. Arousal occurred from both sleep states during rapidly developing hypoxemia but was delayed in active sleep compared to quiet sleep. The arterial Hb oxygen saturation at arousal was significantly lower, and the time to arousal was significantly longer with repeated exposure to hypoxemia during both quiet sleep and active sleep. Naloxone did not alter this arousal response decrement to hypoxemia. Thus, our data provide evidence that endogenous opiates do not play a major role in causing the arousal response decrement that follows repeated exposure to hypoxemia during sleep in lambs.     

Repeated exposure to rapidly developing hypoxemia influences the interaction between oxygen and carbon dioxide in initiating arousal from sleep in lambs

Experiments were done on 12 lambs to determine if repeated exposure to hypoxemia influences the interaction between oxygen and carbon dioxide in causing arousal response from sleep. Each lamb was anesthetized and instrumented for sleep staging and measurements of arterial Hb oxygen saturation. No sooner than 3 days after surgery, measurements were made in quiet and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing either 5% O2-0% CO2, 5% O2-5% CO2 or 5% O2-10% CO2. Each experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen once the animal aroused from sleep. The lambs were divided into two groups. One group (n = 7) was studied without prior exposure to hypoxemia and the other group (n = 5) was studied after exposure to 5% oxygen during approximately 100 epochs of sleep until they aroused. In lambs not previously exposed to hypoxemia, there was evidence for a slight interaction between oxygen and carbon dioxide in initiating arousal but only from quiet sleep. Repeated exposure to hypoxemia resulted in an arousal response decrement to hypoxemia. In lambs previously exposed to hypoxemia, there was evidence for an interaction between oxygen and carbon dioxide in initiating arousal from both quiet and active sleep (i.e. the time to arousal decreased and the saturation at arousal increased as increasing amounts of carbon dioxide were added to the hypoxic gas mixture).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nicotine delays arousal during hypoxemia in lambs

A decreased ability to arouse from sleep in response to arterial hypoxemia may lead to severe asphyxia and has been proposed as a mechanism of sudden infant death syndrome. Based on previous observations that nicotine exposure, a major environmental risk factor for sudden infant death syndrome, may impair hypoxic defense in neonates, we hypothesized that a short-term infusion of nicotine could impair hypoxic arousal through interference with oxygen-sensing mechanisms. Seven chronically instrumented unanesthetized lambs were studied at the age of 4.6 +/- 1.3 d during normoxia and acute hypoxia (0.1 fraction of inspired oxygen) for 5 min. Ventilation, transcutaneous Hb oxygen saturation, blood pressure, heart rate, and time to arousal were compared during a control saline infusion and during a 0.5 microg x kg(-1) x min(-1) nicotine infusion. Activity states, i.e. wakefulness and quiet sleep as well as arousal, were defined by EEG, nuchal electromyogram, and electrooculogram. Each lamb acted as its own control. Arousal from quiet sleep occurred significantly later during nicotine infusion compared with control (177 +/- 93 versus 57 +/- 41 s, p < 0.01) and at a lower transcutaneous Hb oxygen saturation (60 +/- 12 versus 79 +/- 12%, p < 0.01) (paired t test). The ventilatory response to hypoxia in wakefulness was similar during both conditions but was significantly attenuated in quiet sleep during nicotine infusion (p < 0.001, 2-way ANOVA repeated-measures design). Blood pressure and heart rate responses were similar during both conditions. These results suggest that a brief nicotine exposure blunts oxygen sensitivity in young lambs, a finding of potential relevance for sudden infant death syndrome.     

Depression of Respiratory Muscles and Defective Responses to Nasal Obstruction during Active Sleep in the Newborn

Henderson-Smart, D. J. and Read, D. J. C. (1976). Aust. paediat. J. , 12, 261–266. Depression of respiratory muscles and defective responses to nasal obstruction during active sleep in the newborn. Rib-cage and abdominal movements were recorded during different sleep stages in 22 healthy babies at ages up to 3 months and in 8 older infants up to 10 months. During active sleep, all babies and 6 infants developed: (i) rib-cage collapse during diaphragmatic descent; (ii) overall deflation of the rib-cage. Oesophageal pressure recordings in 7 babies showed that this paradoxical rib-cage motion was not accompanied by increased negativity of intra-pleural pressure, and was therefore not due to intermittent airway obstruction.
In 7 newborn lambs, the development of rib-cage paradox during active sleep was related to a marked reduction of the electromyographic (EMG) activity of intercostal and abdominal muscles. During quiet sleep, nasal occlusion initiated a strong reflex augmentation of intercostal EMG activity and prompt arousal, whereas in active sleep these defensive responses were absent. A reduction of pulmonary O₂-stores and ventilation may result during active sleep, making the newborn baby vulnerable to a rapid development of hypoxaemia, respiratory depression and sudden infant death (crib-death).     

Hypoxic and hypercapneic arousal responses and prediction of subsequent apnea in apnea of infancy

Hypoxic and hypercapneic arousal responses from quiet sleep were tested in 56 infants with apnea of infancy (one or more episodes of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation with no treatable cause; age 6.8 +/- 1.1 [SEM] months). Responses were compared with those of nine control infants ranging from 1 to 25 months of age. To assess hypercapneic arousal, the inspired PCO2 was rapidly increased during quiet sleep to 60 mm Hg or until arousal (restlessness, agitation, eye opening) occurred. All control infants and those with apnea of infancy aroused to hypercapnea, but control infants aroused at a lower inspired PCO2 (inspired PCO2 40.1 +/- 2.6 mm Hg) than those with apnea of infancy (inspired PCO2 46.9 +/- 1.5 mm Hg, P less than .05). To assess hypoxic arousal, the inspired PO2 was rapidly decreased during quiet sleep to 80 mm Hg or until arousal occurred. All control infants aroused to hypoxia (inspired PO2 78.3 +/- 2.1 mm Hg). However, only 38% of those with apnea of infancy aroused (inspired PO2 78.1 +/- 0.8 mm Hg), indicating an abnormality in recognition of hypoxia, or central brainstem response to hypoxia. During the 10.4 +/- 1.2 months of follow-up, there was a high incidence of subsequent apneas (greater than 20 seconds) during sleep at home in 50 apneic infants. Infants with abnormal hypoxic arousal responses had more severe subsequent apneas than those with normal hypoxic arousal responses (P less than .05).     

Effects of prior hypoxia exposure, endotoxin and sleep state on arousal ability to airway obstruction in piglets: implications for sudden infant death syndrome

BACKGROUND: Respiratory tract infections may be an important component in many deaths attributed to sudden infant death syndrome (SIDS), although the mechanism of involvement remains unclear. OBJECTIVES: The hypothesis was tested that prolonged hypoxia and a thermogenic state (simulating a fever due to respiratory tract infection) would impair respiratory responsiveness to airway obstruction during sleep. METHODS: Thirty nine piglets aged 5-7 days were exposed to 24 h of moderate hypoxia and/or a low dose of endotoxin derived from Salmonella abortus equi. Responsiveness to complete and subtotal upper airway obstruction was tested during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The end-point for airway obstruction tests was taken as the first protective response, either arousal or initiation of mouth breathing. Responsiveness was assessed as response time and response threshold (measured as respiratory effort, i.e. esophageal pressure swing). RESULTS: All animals demonstrated a thermogenic state following endotoxin delivery (drop in ear temperature of 5.8 +/- 0.2 degrees C and a small but significant increase in rectal temperature). Response time to subtotal airway obstruction was reduced during the heat conserving phase of the fever (thermogenesis; 2.8 +/- 0.5 s compared to 4.3 +/- 0.7 s during pre-endotoxin tests), but markedly increased during the recovery period (20.3 +/- 5.1 compared to 14.0 +/- 2.5 s pre-endotoxin) in NREM sleep. Response threshold was not significantly affected by either endotoxin or hypoxia in NREM sleep. Respiratory responsiveness to subtotal obstruction was markedly reduced during REM sleep (response time 40.3 +/- 10.9 s compared to 14.7 +/- 2.2 s in NREM; response threshold -14.0 +/- 1.3 mm Hg compared to -11.7 +/- 1.0 mm Hg in NREM). CONCLUSIONS: This study has demonstrated in a neonatal animal model that respiratory responsiveness to airways obstruction is delayed during recovery from fever. The findings may have implications for the human infant recovering from a respiratory illness.     

Sleep-dependent changes in the coupling between heart period and arterial pressure in newborn lambs

This study assessed whether sleep-dependent changes in the relationship between heart period (HP) and mean arterial pressure (MAP) occur in newborn life. Electrodes for electrocorticographic, electromyographic, and electrooculographic monitoring and an arterial catheter for blood pressure recordings were implanted in 11 newborn lambs. HP and MAP beat-to-beat values were computed from 120-s blood pressure recordings during quiet wakefulness, active sleep, and quiet sleep. For each recording, the time shift at which the maximum of the HP versus MAP cross-correlation function was attained was identified. For each lamb and wake-sleep state, an average correlation coefficient was then computed corresponding to the median value of such time shifts. The maximum of the cross-correlation function was attained with HP lagging behind MAP. The corresponding mean correlation coefficient was significantly higher in quiet sleep (0.51 +/- 0.05) than either in quiet wakefulness (0.31 +/- 0.05) or in active sleep (0.29 +/- 0.03). Sleep-related differences in the correlation between HP and MAP were maintained after HP and MAP data were low-pass filtered at 0.3 Hz to remove their fast ventilatory oscillations. In conclusion, data indicate that the relationship between spontaneous fluctuations in HP and those in MAP is sleep-state dependent in newborn lambs. A positive HP versus MAP correlation with HP lagging behind MAP is consistent with baroreflex control of HP. Heart rhythm thus may be more tightly controlled by the baroreceptor reflex and less dependent on central autonomic commands in quiet sleep than either in quiet wakefulness or in active sleep.     

Breathing patterns, oxygen and carbon dioxide levels in sleeping healthy infants during the first nine months after birth

Data on arterial oxygen saturation (SaO2), transcutaneous PO2, pCO2 (tcpO2, tcpCO2) and breathing patterns in sleeping healthy term infants were obtained during the first 9 mo after birth. Forty-four healthy infants, mean GA at birth 40 +/- 1.0 wk, mean BW 3520 +/- 562 g were examined between 2 wk and 9 mo postnatally in a cross-sectional study. SaO2, tcpO2, tcpCO2, heart rate (HR), rib cage and abdominal respiratory movements were recorded during natural nocturnal sleep, stratified for sleep states (active sleep (AS), indeterminate sleep (IS), quiet sleep (QS)). The data on AS and IS were pooled as in previous studies. The variables were analysed with respect to age. SaO2 in AS + IS and QS was 96.1 +/- 1.3%, 96.6 +/- 1.4%, respectively. TcpO2 in AS + IS was 10.6 +/- 1.1 kPa and 10.7 +/- 1.3 kPa in QS, while tcpCO2 in AS + IS was 5.4 +/- 0.3 kPa and 5.4 +/- 0.4 kPa in QS. Neither SaO2 nor tcpO2 was influenced by age. TcpCO2 decreased significantly postnatally. Five infants (11.3%) experienced episodes of hypoxaemia with a mean decrease in SaO2 to 86 +/- 1.5%. In four infants these hypoxaemic episodes were linked to upper airway obstructions. Episodes of SaO2 < 90% in conjunction with a decrease in HR to < 100 bpm were detected in one infant only. Periodic breathing (PB) was observed in 38.6% of infants. Conclusion: Oxygenation and carbon dioxide levels in sleeping healthy term infants were comparable to those reported in older children. Hypoxaemic episodes, if present, are associated with upper airway obstruction. PB, often assumed to be a pathological feature, is a normal breathing pattern in this age group.     

Postnatal nicotine exposure does not further compromise hypoxia defense mechanisms in prenatally nicotine-exposed lambs

AIMS: To determine whether combined pre- and postnatal nicotine exposure compared with prenatal exposure alone results in more compromised postnatal hypoxia defense mechanisms and further alteration of the postnatal breathing pattern (reduced tidal volume and increased respiratory rate). METHODS: Seven lambs exposed to nicotine prenatally (pN) (approximate maternal dose: 0.5 mg/kg/d) and seven lambs exposed to nicotine pre- and postnatally (ppN) (postnatal dose: 1.6-2 mg/kg/d) were studied without sedation at an average age of 5 d and 21 d during resting (room air) conditions, during exposure to 10% O2 and during a brief exposure to 100% O2. RESULTS: Resting minute ventilation, occlusion pressure, effective impedance, heart rate and mean arterial blood pressure were similar in the two groups during wakefulness and quiet sleep. Resting tidal volume was significantly higher in ppN than in pN lambs during wakefulness (9.4 +/- 0.7 vs 7.7 +/- 1.4 ml/kg, p < 0.05) and quiet sleep (9.8 +/- 0.6 vs 7.6 +/- 1.5 ml/kg, p < 0.01) at 5 d and also at 21 d during wakefulness (7.7 +/- 1.0 vs 6.2 +/- 1.1 ml/kg, p < 0.05). The ventilatory, heart rate and blood pressure responses to hypoxia were comparable in the two groups during both activity states. Time to arousal from quiet sleep in response to hypoxia was equivalent in the two groups. The ventilatory response to hyperoxia was not significantly different in the two groups during either activity state. CONCLUSION: Continued postnatal nicotine exposure after prenatal exposure did not further compromise hypoxia defense mechanisms after birth.     

Effect of head position on distribution of nasal airflow in preterm infants

Supine preterm infants characteristically adopt a lateral head position; however, it is not known whether this influences the distribution of nasal airflow. Ventilation was measured in 12 healthy preterm infants (postconceptional age 34 +/- 2 weeks) by employing a nasal mask pneumotachygraph that separated airflow between the left and right nasal passages. In the midline supine position, the percent of total tidal volume (%VT) through the right nasal passage ranged from 31% to 64% and varied by less than 5% between active and quiet sleep in any infant. Lateral positioning of the head caused %VT to increase on the dependent side and decrease through the upper nasal passage. When the right side was dependent, mean %VT on that side increased from 52 +/- 9% to 67 +/- 14% (P less than 0.01) and decreased to 43 +/- 10% (P less than 0.05) when the right side was up. In the midline position, the presence of a nasogastric tube caused %VT through the nasal passage with the tube to fall from 54 +/- 8% to 39 +/- 8% (P less than 0.01). The %VT fell farther, to 25 +/- 10% (P less than 0.01), when the nasal passage with the nasogastric tube was up. Despite these changes in VT distribution, total VT remained constant during these maneuvers. We speculate that when supine preterm infants adopt a lateral head position, the decrease in airflow through the upper nasal passage results from partial obstruction of the oropharyngeal or nasopharyngeal airway on that side.     

Ventilatory sensitivity to mild asphyxia: prone versus supine sleep position.

AIMS: To compare the effects of prone and supine sleep position on the main physiological responses to mild asphyxia: increase in ventilation and arousal. METHODS: Ventilatory and arousal responses to mild asphyxia (hypercapnia/hypoxia) were measured in 53 healthy infants at newborn and 3 months of age, during quiet sleep (QS) and active sleep (AS), and in supine and prone sleep positions. The asphyxial test mimicked face down rebreathing by slowly altering the inspired air: CO(2), maximum 5% and O(2), minimum 13.5%. The change in ventilation with inspired CO(2) was measured over 5-6 minutes of the test. The slope of a linear curve fit relating inspired CO(2) to the logarithm of ventilation was taken as a quantitative measure of ventilatory asphyxial sensitivity (VAS). Sleep state and arousal were determined by behavioural criteria. RESULTS: At 3 months of age, prone positioning in AS lowered VAS (0.184 prone v 0.269 supine, p = 0.050). At newborn age, sleep position had no effect on VAS. Infants aged 3 months were twice as likely to arouse to the test than newborns (p = 0.013). Placing infants prone as opposed to supine increased the chances of arousal 1.57-fold (p = 0.035). CONCLUSION: Our findings show 3 month old babies sleeping prone compared to supine have poorer ventilatory responses to mild asphyxia, particularly in AS, but the increased prevalence of arousal is a protective factor.     

Hypoxic airway constriction in infants of very low birth weight recovering from moderate to severe bronchopulmonary dysplasia

We hypothesized that infants recovering from severe bronchopulmonary dysplasia have airway constriction that is, at least in part, related to borderline hypoxia. If this hypothesis were correct, pulmonary resistance should decrease with the administration of oxygen. To test this hypothesis, we studied 10 infants recovering from severe bronchopulmonary dysplasia (study weight 2490 +/- 275 gm; birth weight 1010 +/- 89 gm; postnatal age 73 +/- 7 days; postconceptional age 38.5 +/- 1.6 weeks) and 10 matched control infants (study weight 2430 +/- 179 gm; birth weight 2320 +/- 195 gm; postnatal age 25 +/- 4 days; postconceptional age 37.5 +/- 0.8 weeks). Resistance and compliance were measured by means of a mask with a flowmeter and an esophageal balloon (with the PEDS computer program). Measurements in both groups were made in quiet sleep, without sedation, during the inhalation of room air and during the fifth minute of oxygen inhalation. We found that (1) total pulmonary resistance, significantly higher in infants with bronchopulmonary dysplasia than in control infants, decreased from 206.1 +/- 47 cm H2O.L-1.sec-1 during inhalation of room air to 106.5 +/- 20.9 during inhalation of 100% oxygen (p less than 0.05) and (2) pulmonary dynamic compliance, lower in infants with bronchopulmonary dysplasia than in control infants, increased significantly with the administration of 100% oxygen. The results suggest that infants with bronchopulmonary dysplasia have airway constriction and that this is alleviated by inhalation of oxygen.     

A developmental study on types and frequency distribution of short apneas (3 to 15 seconds) in term and preterm infants

We measured the frequency distribution and the ventilatory correlates of the various types of apneas 3 to 15 s long during sleep in eight term infants (birth weight 3.65 +/- 0.16 kg; gestational age 39.5 +/- 0.3 wk) and eight preterm infants (birth weight 2.07 +/- 0.18 kg; gestational age 34.3 +/- 0.4 wk). Each infant was studied on five to seven occasions from birth to 56 wk of postconceptual age using a modified flow-through system. Sixty-six paired epochs of quiet sleep (1163 min) and rapid eye movement sleep (829 min) were analyzed in term infants and 85 paired epochs of quiet sleep (1553 min) and rapid eye movement sleep (1328 min) in preterm infants. Of the 783 apneas recorded in term infants 82% were central, 1.5% obstructive, 0.5% mixed, and 16% were of the breath-holding type; the corresponding figures for the 4086 apneas recorded in preterm infants were 93, 0.5, 1.0, and 5.5%. This distribution was similar in the two sleep states but term infants had a higher percentage of breath-holding apneas than preterm infants (p less than 0.01). In preterm infants the rate of central apneas decreased with postnatal age (p less than 0.01); in term infants the rate did not change significantly. The duration of apneas showed a modal distribution for central apneas at about 8 s for both groups during the 1st month of life (p less than 0.05). The findings suggest: 1) apneas in the newborn and early infancy are primarily central and are more frequent in preterm than in term infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Infant stress and sleep deprivation as an aetiological basis for the sudden infant death syndrome

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.     

Hypoxic arousal responses in infants with bronchopulmonary dysplasia

Infants with bronchopulmonary dysplasia have a high incidence of sudden, unexplained death in the postneonatal period, yet the cause of these deaths is unknown. Frequent episodes of clinically unsuspected arterial oxygen desaturation have recently been described in infants with bronchopulmonary dysplasia. We hypothesized that infants with bronchopulmonary dysplasia who experience frequent episodes of hypoxia may have abnormal arousal responses to these hypoxic episodes. We studied 12 infants with bronchopulmonary dysplasia at 41.4 +/- 1.3 weeks postconceptional age. Hypoxic arousal responses were performed during quiet sleep at an inspired oxygen tension of 80 mm Hg for a maximum of three minutes or until arousal occurred. Of 12 infants, 11 (92%) aroused normally to the hypoxic challenge. However, all infants required vigorous stimulation and supplemental oxygen after the initial arousal response. Of 12 infants with bronchopulmonary dysplasia, eight (67%) experienced prolonged apnea with bradycardia, and four of 12 (33%) required brief ventilatory assistance (bag and mask) to restore normal breathing. Abnormal pneumographic findings did not predict the occurrence of these prolonged periods of apnea and bradycardia following hypoxia. We conclude that an abnormal response to hypoxia following arousal may lead to prolonged apnea and bradycardia in infants with bronchopulmonary dysplasia. We speculate that the inability to recover from this hypoxia may result in sudden death in these infants.     

Decreased specific airway conductance in infant apnea

A disorder of respiratory control is the suspected etiology in a majority of infants with apnea. Although neurologic control of breathing has been evaluated in infants surviving an apneic episode, pulmonary mechanics have not been previously measured. Pulmonary mechanics were measured during sleep in ten infants with apnea, aged 45.4 +/- 1.4 (SE) weeks postconception, and 13 control infants, aged 42.0 +/- 0.8 weeks postconception. Infant apnea patients were defined as those having at least one episode of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation to restore normal breathing, and in whom no treatable etiology could be found. Thoracic gas volume, airway resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured in six infants using an esophageal balloon. Specific airway conductance was decreased in infants with apnea compared with control infants (P less than .05). Thoracic gas volume, airway resistance, and dynamic pulmonary compliance values were comparable with those of control infants. These data suggest that airway narrowing or abnormal control of airway tone during sleep may contribute to apnea in some infants.     

Arterial oxygen tension threshold range for the onset of arousal and breathing in fetal sheep.

Mechanisms for the control of episodic fetal breathing movements or the onset of continuous breathing at birth remain unknown. Lung distension with 100% O2 at a continuous positive airway pressure of 30 cm H2O may induce arousal and continuous breathing. To investigate 1) the threshold range of arterial oxygen tension (PaO2) for the onset of arousal and breathing and 2) the graded response of breathing to various levels of PaO2, we studied 10 fetal sheep between 135 and 142 d of gestation (term = 147 +/- 2 d). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, arterial pH, and blood gas tensions. PaO2 threshold was determined through an indwelling O2 sensor catheter. Fetal lungs were distended at a continuous positive airway pressure of 40 cm H2O with 100% N2 or with O2 ranging from 40 to 100% via an in situ endotracheal tube. At the onset of arousal (n = 10), PaO2, arterial carbon dioxide tension, and Hb O2 saturation increased from control values of 21.7 +/- 0.75 torr (2.9 +/- 0.09 kPa), 41.8 +/- 1.1 torr (5.47 +/- 0.15 kPa), and 52.9 +/- 2.6% to 65.6 +/- 9.6 torr (8.74 +/- 1.28 kPa), 46.9 +/- 1.3 torr (6.25 +/- 0.17 kPa), and 92.9 +/- 2.06%, respectively, whereas the pH decreased from 7.31 +/- 0.006 to 7.27 +/- 0.009 (mean +/- SEM; p = 0.001, 0.04, 0.002, and 0.001, respectively). Seven of 10 fetuses breathed continuously. In these fetuses, PaO2 and arterial carbon dioxide tension further increased and pH decreased; however, no further significant increase in Hb O2 saturation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)