Mechanism underlying accelerated arterial oxygen desaturation during recurrent apnea.

Rationale: Brief recurrent apneas in preterm infants and adults can precipitate rapid and severe arterial O(2) desaturation for reasons that remain unclear.

Objectives: We tested a mathematically derived hypothesis that when breathing terminates apnea, mixed-venous hypoxemia continues into the subsequent apnea; as a result, there is a surge in pulmonary O(2) uptake that rapidly depletes the finite alveolar O(2) store, thereby accelerating arterial O(2) desaturation.

Methods: Recurrent apneas were simulated in an experimental lamb model.

A dynamic model for assessing the impact of diffusing capacity on arterial oxygenation during apnea.

Preterm infants have a reduced pulmonary diffusing capacity that has been invoked to explain rapid arterial O(2)-desaturation during apnea, despite little evidence to support this view. We explored the role of diffusion limitation on O(2)-desaturation during apnea by developing a mathematical model of gas exchange in which O(2) dynamically loads the blood traversing the pulmonary capillary. While normal diffusing capacity DL((O(2)) had negligible impact on apneic desaturation, reduced DL((O(2)) advanced the onset of desaturation during apnea.

A model investigation of the impact of ventilation-perfusion mismatch on oxygenation during apnea in preterm infants.

Ventilation-perfusion (V/Q) mismatch is a prominent feature of preterm infants and adults with lung disease. V/Q mismatch is known to cause arterial hypoxemia under steady-state conditions, and has been proposed as the cause of rapid arterial oxygen desaturation during apnea. However, there is little evidence to support a role for V/Q mismatch in the dynamic changes in arterial oxygenation that occur during apnea.

New acoustic method for detecting upper airway obstruction in patients with sleep apnoea.

Unlabelled: This article investigates a new acoustic device to assess the behaviour of the upper airway in patients with OSA. Currently there is no simple non-invasive method to perform such measurements. As such this paper describes the device in probing the patency of the airway during sleep and increasing the efficiency of diagnosing OSA.

A model analysis of arterial oxygen desaturation during apnea in preterm infants.

Rapid arterial O(2) desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O(2) desaturation during apnea (Sa(O)₂) is complicated by the non-linear O(2) dissociation curve, falling pulmonary O(2) uptake, and by the fact that O(2) desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O(2) consumption accelerates Sa(O)₂throughout the entire desaturation process.

Maturation of respiratory control and the propensity for breathing instability in a sheep model.

Limited evidence suggests that the ventilatory interaction between O(2) and CO(2) is additive after birth and becomes multiplicative with postnatal development. Such a switch may be linked to the propensity for periodic breathing (PB) in infancy. To test this idea, we characterized the maturation of the respiratory controller and its effect on breathing stability in approximately 10-day-old lambs and 6-mo-old sheep.

Continuous positive airway pressure reduces loop gain and resolves periodic central apneas in the lamb.

Continous positive airway pressure (CPAP) is used to treat infant respiratory distress syndrome and apnea of prematurity, but its mode of action is not fully understood. We hypothesised that CPAP increases lung volume and stabilises respiratory control by decreasing loop gain (LG). Experimentally induced periodic breathing (PB) in the lamb was terminated early by CPAP in a dose-dependent manner, with a control epoch of 45.

Increased peripheral chemosensitivity via dopaminergic manipulation promotes respiratory instability in lambs.

Periodic breathing (PB) is an instability of the respiratory control system believed to be mediated principally by the peripheral chemoreceptors. We hypothesised that domperidone, a dopamine D(2)-receptor antagonist that increases carotid body sensitivity to O(2) and CO(2), would promote PB through an increase in the loop gain (LG) of the respiratory control system. Domperidone significantly increased controller gain for oxygen (p<0.

Postnatal development of periodic breathing cycle duration in term and preterm infants.

Previous studies of the maturation of periodic breathing cycle duration (PCD) with postnatal age in infants have yielded conflicting results. PCD is reported to fall in term infants over the first 6 mo postnatally, whereas in preterm infants PCD is reported either not to change or to fall. Contrary to measured values, use of a theoretical respiratory control model predicts PCD should increase with postnatal age.

The effects of repeated exposure to hypercapnia on arousal and cardiorespiratory responses during sleep in lambs.

Arousal and cardio-respiratory responses to respiratory stimuli during sleep are important protective mechanisms that rapidly become depressed in the active sleep state when episodes of hypoxia or asphyxia are repeated: whether responses to repeated hypercapnia are similarly depressed is not known. This study aimed to determine if arousal and cardio-respiratory responses also become depressed with repeated episodes of hypercapnia during sleep and whether responses differ in active sleep and quiet sleep. Eight newborn lambs were instrumented to record sleep state and cardio-respiratory variables.

Velocity and attenuation of sound in the isolated fetal lung as it is expanded with air.

We measured the velocity and attenuation of audible sound in the isolated lung of the near-term fetal sheep to test the hypothesis that the acoustic properties of the lung provide a measure of the volume of gas it contains. We introduced pseudorandom noise (bandwidth 70 Hz-7 kHz) to one side of the lung and recorded the noise transmitted to the surface immediately opposite, starting with the lung containing only fetal lung liquid and making measurements after stepwise inflation with air until a leak developed. The velocity of sound in the lung fell rapidly from 187 +/- 28.

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb.

We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in seven lambs following posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or loop gain (LG) of the respiratory control system of the lamb is directly proportional to the difference between alveolar PO2 and inspired PO2. This analysis indicates that during PB, when by necessity LG is >1, replacement of the inspired gas with one of reduced PO2 lowers LG; if we made inspired PO2 approximate alveolar PO2, we predict that LG would be approximately zero and breathing would promptly stabilize.