Dynamic loop gain increases upon adopting the supine body position during sleep in patients with obstructive sleep apnoea.

Background And Objective: Obstructive sleep apnoea (OSA) is typically worse in the supine versus lateral sleeping position. One potential factor driving this observation is a decrease in lung volume in the supine position which is expected by theory to increase a key OSA pathogenic factor: dynamic ventilatory control instability (i.e.

Control theory prediction of resolved Cheyne-Stokes respiration in heart failure.

Cheyne-Stokes respiration (CSR) foretells deleterious outcomes in patients with heart failure. Currently, the size of therapeutic intervention is not guided by the patient's underlying pathophysiology. In theory, the intervention needed to resolve CSR, as a control system instability (loop gain >1), can be predicted knowing the baseline loop gain and how much it falls with therapy.

The effect of prenatal maternal infection on respiratory function in mouse offspring: evidence for enhanced chemosensitivity.

Systemic maternal inflammation is implicated in preterm birth and bronchopulmonary dysplasia (BPD) and may induce morbidities including reduced pulmonary function, sleep-disordered breathing, and cardiovascular disorders. Here we test the hypothesis that antenatal maternal inflammation per se causes altered alveolar development and increased chemoreflex sensitivity that persists beyond infancy. Pregnant C57BL/6 mice were administered lipopolysaccharide (LPS) (150 μg/kg ip) to induce maternal inflammation or saline (SHAM) at embryonic day 16 (randomized).

The Effect of Body Position on Physiological Factors that Contribute to Obstructive Sleep Apnea.

Study Objectives: Obstructive sleep apnea (OSA) resolves in lateral sleep in 20% of patients. However, the effect of lateral positioning on factors contributing to OSA has not been studied. We aimed to measure the effect of lateral positioning on the key pathophysiological contributors to OSA including lung volume, passive airway anatomy/collapsibility, the ability of the airway to stiffen and dilate, ventilatory control instability (loop gain), and arousal threshold.

A randomised crossover trial of clinical algorithm for oxygen saturation targeting in preterm infants with frequent desaturation episodes.

Objectives: Strategies for oxygen therapy for preterm infants, such as the Vermont-Oxford's 'Breathsavers' guidelines, seek to strike a balance between the potential risks of the extremes of hyperoxia and hypoxia in preterm infants. Using an algorithm based on those guidelines, we aimed to compare the proportion of time spent within the SpO2 target range during algorithm-based management of oxygen delivery compared with routine nursing care.

Study Design: In a randomised crossover trial, maintenance of SpO2 over a 4-hour period during routine care was compared with algorithm-based control (administered by a dedicated research nurse).

Interleukin-1 receptor antagonist prevents murine bronchopulmonary dysplasia induced by perinatal inflammation and hyperoxia.

Bronchopulmonary dysplasia (BPD) is a common lung disease of premature infants, with devastating short- and long-term consequences. The pathogenesis of BPD is multifactorial, but all triggers cause pulmonary inflammation. No therapy exists; therefore, we investigated whether the anti-inflammatory interleukin-1 receptor antagonist (IL-1Ra) prevents murine BPD.

Loop gain as a means to predict a positive airway pressure suppression of Cheyne-Stokes respiration in patients with heart failure.

Rationale: Patients with heart failure (HF) and Cheyne-Stokes respiration or periodic breathing (PB) often demonstrate improved cardiac function when treatment with continuous positive airway pressure (CPAP) resolves PB. Unfortunately, CPAP is successful in only 50% of patients, and no known factor predicts responders to treatment. Because PB manifests from a hypersensitive ventilatory feedback loop (elevated loop gain [LG]), we hypothesized that PB persists on CPAP when LG far exceeds the critical threshold for stable ventilation (LG = 1).

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.

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.

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.

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.