Publications

We aimed to characterize the cerebral hemodynamic response to obstructive sleep apnea/hypopnea events, and evaluate their association to polysomnographic parameters. The characterization of the cerebral hemodynamics in obstructive sleep apnea (OSA) may add complementary information to further the understanding of the severity of the syndrome beyond the conventional polysomnography.Severe OSA patients were studied during night sleep while monitored by polysomnography. Transcranial, bed-side diffuse correlation spectroscopy (DCS) and frequency-domain near-infrared diffuse correlation spectroscopy (NIRS-DOS) were used to follow microvascular cerebral hemodynamics in the frontal lobes of the cerebral cortex. Changes in cerebral blood flow (CBF), total hemoglobin concentration (THC), and cerebral blood oxygen saturation (StO2) were analyzed.We considered 3283 obstructive apnea/hypopnea events from sixteen OSA patients (Age (median, interquartile range) 57 (52-64.5); females 25%; AHI (apnea-hypopnea index) 84.4 (76.1-93.7)). A biphasic response (maximum/minimum followed by a minimum/maximum) was observed for each cerebral hemodynamic variable (CBF, THC, StO2), heart rate and peripheral arterial oxygen saturation (SpO2). Changes of the StO2 followed the dynamics of the SpO2, and were out of phase from the THC and CBF. Longer events were associated with larger CBF changes, faster responses and slower recoveries. Moreover, the extrema of the response to obstructive hypopneas were lower compared to apneas (p < .001).Obstructive apneas/hypopneas cause profound, periodic changes in cerebral hemodynamics, including periods of hyper- and hypo-perfusion and intermittent cerebral hypoxia. The duration of the events is a strong determinant of the cerebral hemodynamic response, which is more pronounced in apnea than hypopnea events.© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.

JTD Keywords: cerebral hemodynamics, desaturation, diffuse correlation spectroscopy, duration, hypopnea, hypoxemia, near-infrared spectroscopy, optical pathlength, oxygenation, severity, sleep disorder, spectroscopy, tissue, Adult, Airway obstruction, Apnea hypopnea index, Arterial oxygen saturation, Article, Blood oxygen tension, Blood-flow, Brain blood flow, Brain cortex, Cerebral hemodynamics, Controlled study, Diffuse correlation spectroscopy, Disease severity, Female, Frequency, Frontal lobe, Heart rate, Hemodynamics, Hemoglobin, Hemoglobin determination, Human, Humans, Major clinical study, Male, Near infrared spectroscopy, Near-infrared spectroscopy, Obstructive sleep apnea, Oxygen, Periodicity, Polysomnography, Sleep apnea syndromes, Sleep apnea, obstructive, Sleep disorder, Spectroscopy, near-infrared

JTD Keywords: Airway obstruction, Lung function, Non-invasive technique, Respiratory resistance, Vocal cord dysfunction

Rat model of Obstructive Sleep Apnea (OSA) is a realistic approach for studying physiological mechanisms involved in sleep. Rats are usually anesthetized and autonomic nervous system (ANS) could be blocked. This study aimed to assess the effect of anesthesia on ANS activity during OSA episodes. Seven male Sprague-Dawley rats were anesthetized intraperitoneally with urethane (1g/kg). The experiments were conducted applying airway obstructions, simulating 15s-apnea episodes for 15 minutes. Five signals were acquired: respiratory pressure and flow, SaO2, ECG and photoplethysmography (PPG). In total, 210 apnea episodes were studied. Normalized power spectrum of Pulse Rate Variability (PRV) was analyzed in the Low Frequency (LF) and High Frequency (HF) bands, for each episode in consecutive 15s intervals (before, during and after the apnea). All episodes showed changes in respiratory flow and SaO₂ signal. Conversely, decreases in the amplitude fluctuations of PPG (DAP) were not observed. Normalized LF presented extremely low values during breathing (median=7,67%), suggesting inhibition of sympathetic system due to anesthetic effect. Subtle increases of LF were observed during apnea. HRV and PPG analysis during apnea could be an indirect tool to assess the effect and deep of anesthesia.

JTD Keywords: electrocardiography, fluctuations, medical disorders, medical signal detection, medical signal processing, neurophysiology, photoplethysmography, pneumodynamics, sleep, ECG, SaO₂ flow, SaO₂ signal, airway obstructions, amplitude fluctuations, anesthesia effects, anesthetized nervous system, autonomic evaluation, autonomic nervous system, breathing, heart rate variability, high-frequency bands, low-frequency bands, male Sprague-Dawley rats, normalized power spectrum, obstructive sleep apnea, photoplethysmography, physiological mechanisms, pulse rate variability, rat model, respiratory flow, respiratory pressure, signal acquisition, sympathetic system inhibition, time 15 min, time 15 s, Abstracts, Atmospheric modeling, Computational modeling, Electrocardiography, Rats, Resonant frequency

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstructions during sleep. The most common animal model of OSA is based on subjecting rodents to intermittent hypoxic exposures and does not mimic important OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To circumvent some of these issues, a novel murine model involving non-invasive application of recurrent airway obstructions was developed. An electronically controlled airbag system is placed in front of the mouse's snout, whereby inflating the airbag leads to obstructed breathing and spontaneous breathing occurs with the airbag deflated. The device was tested on 29 anesthetized mice by measuring inspiratory effort and arterial oxygen saturation (SaO(2)). Application of recurrent obstructive apneas (6s each, 120/h) for 6h resulted in SaO(2) oscillations to values reaching 84.4 +/- 2.5% nadir, with swings mimicking OSA patients. This novel system, capable of applying controlled recurrent airway obstructions in mice, is an easy-to-use tool for investigating pertinent aspects of OSA.

JTD Keywords: Animal model, Upper airway Obstruction, Mouse model, Non-invasive system, Model sleep apnea, Respiratory disease

The aim was to test the hypothesis that mesenchymal stem cells (MSC) could reduce the inflammation induced by recurrent airway occlusions in an animal model of obstructive sleep apnea (OSA). A nasal mask was applied to 30 anesthetized rats. Twenty rats were subjected to a pattern of recurrent obstructive apneas mimicking OSA (60/h, lasting 15 s each) for 5h. MSC (5x10(6) cells) were intravenously injected into 10 of these rats. Ten rats not subjected to apneas or MSC injection were used as controls. The rat blood serum concentrations of pro-inflammatory cytokine IL-1beta were measured by ELISA. IL-1beta was significantly greater in the rats subjected to recurrent apneas (66.7+/-41.2 pg/mL; m+/-SEM) than in controls (1.9+/-1.0 pg/mL; p<0.05). In the group of apneic rats subjected to MSC injection, IL-1beta was significantly reduced (6.1+/-3.8 pg/mL; p<0.05). In conclusion, MSC triggered an early anti-inflammatory response in rats subjected to recurrent obstructive apneas, suggesting that these stem cells could play a role in the physiological response to counterbalance inflammation in OSA.

JTD Keywords: Obstructive sleep apnea, Animal model, Airway obstruction, Inflammation

New techniques for automatic invasive and noninvasive identification of inspiratory flow limitation (IFL) are presented. Data were collected from 11 patients with full nocturnal polysomnography and gold-standard esophageal pressure (Pes) measurement. A total of 38,782 breaths were extracted and automatically analyzed. An exponential model is proposed to reproduce the relationship between Pes and airflow of an inspiration and achieve an objective assessment of changes in upper airway obstruction. The characterization performance of the model is appraised with three evaluation parameters: mean-squared error when estimating resistance at peak pressure, coefficient of determination, and assessment of IFL episodes. The model's results are compared to the two best-performing models in the literature. The obtained gold-standard IFL annotations were then employed to train, test, and validate a new noninvasive automatic IFL classification system. Discriminant analysis, support vector machines, and Adaboost algorithms were employed to objectively classify breaths noninvasively with features extracted from the time and frequency domains of the breaths' flowpatterns. The results indicated that the exponential model characterizes IFL and subtle relative changes in upper airway obstruction with the highest accuracy and objectivity. The new noninvasive automatic classification system also succeeded in identifying IFL episodes, achieving a sensitivity of 0.87 and a specificity of 0.85.

JTD Keywords: Esophageal pressure, Exponential model, Inspiratory flow limitation, Noninvasive, Classification, Upper airway obstruction

Study Objectives: To implement a chronic rat model of recurrent airway obstructions to study the obstructive sleep apnea (OSA) syndrome. Design: Prospective controlled animal study. Setting: University laboratory. Patients or Participants: 24 male Sprague-Dawley rats (250-300 g). Interventions: The rats were placed in a setup consisting of a body chamber and a head chamber separated by a neck collar specially designed to apply recurrent airway obstructions with OSA patterns. Rats in the Obstruction group (n=8) were subjected to 5-s obstructions at a rate of 60 per hour, 6 h/day during 4 weeks. Sham rats (n=8) were placed in the setup but no obstructions were applied. Naive rats (n=8) were subjected to no intervention. Measurements and Results: Breathing flow, pressure, CO2 air concentration, and SpO(2) showed that the model mimicked OSA respiratory events (obstructive apneas, increased respiratory efforts, and oxygen saturation dips). Animal stress, assessed by body weight and plasma corticosterone, was not significantly different across Obstruction and Sham groups. This supports the concept that this novel model does not introduce a significant burden of stress in the rat after acclimatization to the chamber. Thromboxane-B2/6-keto-Prostaglandin-F1a ratio in plasma, which is an index of vasoconstriction, was significantly increased in the rats subjected to obstructions. Conclusions: The designed animal model of chronic recurrent airway obstructions is feasible and potentially useful to study the mechanisms involved in the cardiovascular consequences of OSA.

JTD Keywords: Obstructive sleep apnea, Animal model, Airway obstruction