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

Obstructive sleep apnea (OSA) is a sleep disorder in which repetitive upper airway obstructive events occur during sleep. These events can induce hypoxia, which is a risk factor for multiple cardiovascular and cerebrovascular diseases. Chronic obstructive pulmonary disease (COPD) is a disorder which induces a persistent inflammation of the lungs. This condition produces hypoventilation, affecting the blood oxygenation, and leads to an increased risk of developing lung cancer and heart disease. In this study, we evaluated how COPD affects the severity and characteristics of OSA in a multivariate demographic database including polysomnographic signals. Results showed SpO2 subtle variations, such as more non-recovered desaturations and increased time below a 90% SpO2 level, which, in the long term, could worsen the risk to suffer cardiovascular and cerebrovascular diseases.Clinical Relevance - COPD increases the OSA risk due to hypoventilation and altered SpO2 behavior. © 2021 IEEE.

JTD Keywords: Chronic obstructive lung disease, Complication, Epidemiologic studies, Epidemiology, Human, Humans, Oxygen saturation, Pulmonary disease, chronic obstructive, Sleep apnea, obstructive, Sleep disordered breathing, Syndrome

Patients suffering from obstructive sleep apnea (OSA) usually present an increased sympathetic activity caused by the intermittent hypoxia effect on autonomic control. This study evaluated the relationship between sleep stages and the apnea duration, frequency, and type, as well as their impact on HRV markers in different groups of disease severity. The hypnogram and R-R interval signals were extracted in 81 OSA patients from night polysomnographic (PSG) recordings. The apnea-hypopnea index (AHI) defined patient classification as mild-moderate (AHI< 30, n 44) or severe (AHI>30, n 37). The normalized power in VLH, LF, and HF bands of RR series were estimated by a time-frequency approach and averaged in 1-min epochs of normal and apnea segments. The autonomic response and the impact of sleep stages were assessed in both segments to compare patient groups. Deeper sleep stages (particularly S2) concentrated the shorter and mild apnea episodes (from 10 to 40 s) compared to light (SWS) and REM sleep. Longer episodes (>50 s) although less frequent, were of similar incidence in all stages. This pattern was more pronounced for the group of severe patients. Moreover, during apnea segments, LF nu was higher (p 0.044) for the severe group, since V LF nu and HF nu presented the greatest changes when compared to normal segments. The non-REM sleep seems to better differentiate OSA patients groups, particularly through VLF nu and HF nu (p<0.001). A significant difference in both sympathetic and vagal modulation between REM and non-REM sleep was only found within the severe group. These results confirm the importance of considering sleep stages for HRV analysis to further assess OSA disease severity, beyond the traditional and clinically limited AHI values.Clinical relevance - Accounting for sleep stages during HRV analysis could better assess disease severity in OSA patients. © 2021 IEEE.

JTD Keywords: blood-pressure, genomic consequences, intermittent hypoxia, rapid-eye-movement, sympathetic activity, Heart rate, Heart-rate-variability, Human, Humans, Polysomnography, Rem sleep, Sleep apnea, obstructive, Sleep disordered breathing, Sleep stage, Sleep stages, Sleep, rem

STUDY OBJECTIVES: To investigate whether noninvasive application of recurrent airway obstructions induces early release of mesenchymal stem cells into the circulating blood in a rat model of obstructive sleep apnea. DESIGN: Prospective controlled animal study. SETTING: University laboratory. PATIENTS OR PARTICIPANTS: Twenty male Sprague-Dawley rats (250-300 g). INTERVENTIONS: A specially designed nasal mask was applied to the anesthetized rats. Ten rats were subjected to a pattern of recurrent obstructive apneas (60 per hour, lasting 15 seconds each) for 5 hours. Ten anesthetized rats were used as controls. MEASUREMENTS AND RESULTS: Mesenchymal stem cells from the blood and bone marrow samples were isolated and cultured to count the total number of colony-forming unit fibroblasts (CFU-F) of adherent cells after 9 days in culture. The number of CFU-F from circulating blood was significantly (P = 0.02) higher in the rats subjected to recurrent obstructive apneas (5.00 +/- 1.16; mean +/- SEM) than in controls (1.70 +/- 0.72). No significant (P = 0.54) differences were observed in CFU-F from bone marrow. CONCLUSIONS: Application of a pattern of airway obstructions similar to those experienced by patients with sleep apnea induced an early mobilization of mesenchymal stem cells into circulating blood.

JTD Keywords: Adipocytes/cytology, Animals, Blood Cell Count, Bone Marrow Cells/ cytology, Cell Adhesion/physiology, Cell Count, Cell Differentiation/physiology, Cell Division/physiology, Disease Models, Animal, Fibroblasts/cytology, Male, Mesenchymal Stem Cells/ cytology, Osteocytes/cytology, Rats, Rats, Sprague-Dawley, Sleep Apnea, Obstructive/ blood, Stem Cells/cytology