MELANIA DIRCE OLIVEIRA MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Loop gain in REM versus non-REM sleep using CPAP manipulation: A pilot study(2019) MESSINEO, Ludovico; TARANTO-MONTEMURRO, Luigi; AZARBARZIN, Ali; MARQUES, Melania; CALIANESE, Nicole; WHITE, David P.; WELLMAN, Andrew; SANDS, Scott A.
- Broadband Sound Administration Improves Sleep Onset Latency in Healthy Subjects in a Model of Transient Insomnia(2017) MESSINEO, Ludovico; TARANTO-MONTEMURRO, Luigi; SANDS, Scott A.; MARQUES, Melania D. Oliveira; AZABARZIN, Ali; WELLMAN, David AndrewBackground: Insomnia is a major public health problem in western countries. Previous small pilot studies showed that the administration of constant white noise can improve sleep quality, increase acoustic arousal threshold, and reduce sleep onset latency. In this randomized controlled trial, we tested the effect of surrounding broadband sound administration on sleep onset latency, sleep architecture, and subjective sleep quality in healthy subjects. Methods: Eighteen healthy subjects were studied with two overnight sleep studies approximately one week apart. They were exposed in random order to normal environmental noise (40.1 [1.3] dB) or to broadband sound administration uniformly distributed in the room by two speakers (46.0 [0.9] dB). To model transient insomnia, subjects went to bed (""lights out"") 90 min before usual bedtime. Results: Broadband sound administration reduced sleep onset latency to stage 2 sleep (time from lights out to first epoch of non-rapid eye movement-sleep stage 2) (19 [16] vs. 13 [23] min, p = 0.011; median reduction 38% baseline). In a subgroup reporting trouble initiating sleep at home (Pittsburgh Sleep Quality Index section 2 score = 1), sound administration improved subjective sleep quality (p = 0.037) and the frequency of arousals from sleep (p = 0.03). Conclusion: In an experimental model of transient insomnia in young healthy individuals, broadband sound administration significantly reduced sleep onset latency by 38% compared to normal environmental noise. These findings suggest that broadband sound administration might be helpful to minimize insomnia symptoms in selected individuals.
- Retropalatal and retroglossal airway compliance in patients with obstructive sleep apnea(2018) MARQUES, Melania; GENTA, Pedro R.; AZARBARZIN, Ali; SANDS, Scott A.; TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; WHITE, David P.; WELLMAN, AndrewObjectives: We hypothesized that preferential retropalatal as compared to retroglossal collapse in patients with obstructive sleep apnea was due to a narrower retropalatal area and a higher retropalatal compliance. Patients with a greater retropalatal compliance would exhibit a recognizable increase in negative effort dependence (NED). Methods: Fourteen patients underwent upper airway endoscopy with simultaneous recordings of airflow and pharyngeal pressure during natural sleep. Airway areas were obtained by manually outlining the lumen. Compliance was calculated by the change of airway area from end-expiration to a pressure swing of -5 cm H2O. NED was quantified for each breath as [peak inspiratory flow minus flow at -5 cm H2O]/[peak flow] x 100. Results: Compared to the retroglossal airway, the retropalatal airway was smaller at end-expiration (p < 0.001), and had greater absolute and relative compliances (p < 0.001). NED was positively associated with retropalatal relative area change (r = 0.47; p < 0.001). Conclusions: Retropalatal airway is narrower and more collapsible than retroglossal airway. Retropalatal compliance is reflected in the clinically-available NED value.
- The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity A Randomized, Placebo-controlled, Double-Blind Crossover Trial(2019) TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; SANDS, Scott A.; AZARBARZIN, Ali; MARQUES, Melania; EDWARDS, Bradley A.; ECKERT, Danny J.; WHITE, David P.; WELLMAN, AndrewRationale: There is currently no effective pharmacological treatment for obstructive sleep apnea (OSA). Recent investigations indicate that drugs with noradrenergic and antimuscarinic effects improve genioglossus muscle activity and upper airway patency during sleep. Objectives: We aimed to determine the effects of the combination of a norepinephrine reuptake inhibitor (atomoxetine) and an antimuscarinic (oxybutynin) on OSA severity (apnea-hypopnea index [AHI]; primary outcome) and genioglossus responsiveness (secondary outcome) in people with OSA. Methods: A total of 20 people completed a randomized, placebo-controlled, double-blind, crossover trial comparing 1 night of 80 mg atomoxetine plus 5 mg oxybutynin (ato-oxy) to placebo administered before sleep. The AHI and genioglossus muscle responsiveness to negative esophageal pressure swings were measured via in-laboratory polysomnography. In a subgroup of nine patients, the AHI was also measured when the drugs were administered separately. Measurements and Main Results: The participants' median (interquartile range) age was 53 (46-58) years and body mass index was 34.8 (30.0-40.2) kg/m(2). ato-oxy lowered AHI by 63% (34-86%), from 28.5 (10.9-51.6) events/h to 7.5 (2.4-18.6) events/h (P < 0.001). Of the 15/20 patients with OSA on placebo (AHI > 10 events/hr), AHI was lowered by 74% (62-88%) (P < 0.001) and all 15 patients exhibited a >= 50% reduction. Genioglossus responsiveness increased approximately threefold, from 2.2 (1.1-4.7)%/cm H2O on placebo to 6.3 (3.0 to 18.3)%/cm H2O on ato-oxy (P < 0.001). Neither atomoxetine nor oxybutynin reduced the AHI when administered separately. Conclusions: A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on 1 night greatly reduced OSA severity. These findings open new possibilities for the pharmacologic treatment of OSA.
- Breath-holding as a means to estimate the loop gain contribution to obstructive sleep apnoea(2018) MESSINEO, Ludovico; TARANTO-MONTEMURRO, Luigi; AZARBARZIN, Ali; MARQUES, Melania D. Oliveira; CALIANESE, Nicole; WHITE, David P.; WELLMAN, Andrew; SANDS, Scott A.Increased ""loop gain"" of the ventilatory control system promotes obstructive sleep apnoea (OSA) in some patients and offers an avenue for more personalized treatment, yet diagnostic tools for directly measuring loop gain in the clinical setting are lacking. Here we test the hypothesis that elevated loop gain during sleep can be recognized using voluntary breath-hold manoeuvres during wakefulness. Twenty individuals (10 OSA, 10 controls) participated in a single overnight study with voluntary breath-holding manoeuvres performed during wakefulness. We assessed (1) maximal breath-hold duration, and (2) the ventilatory response to 20 s breath-holds. For comparison, gold standard loop gain values were obtained during non-rapid eye movement (non-REM) sleep using the ventilatory response to 20 s pulses of hypoxic-hypercapnic gas (6% CO2-14% O-2, mimicking apnoea). Continuous positive airway pressure (CPAP) was used to maintain airway patency during sleep. Additional measurements included gold standard loop gain measurement during wakefulness and steady-state loop gain measurement during sleep using CPAP dial-ups. Higher loop gain during sleep was associated with (1) a shorter maximal breath-hold duration (r(2) = 0.49, P < 0.001), and (2) a larger ventilatory response to 20 s breath-holds during wakefulness (second breath; r(2) = 0.50, P < 0.001); together these factors combine to predict high loop gain (receiver operating characteristic area-under-curve: 92%). Gold standard loop gain values were remarkably similar during wake and non-REM sleep. The results show that elevated loop gain during sleep can be identified using simple breath-holding manoeuvres performed during wakefulness. This may have implications for personalizing OSA treatment.
- Structure and severity of pharyngeal obstruction determine oral appliance efficacy in sleep apnoea(2019) MARQUES, Melania; GENTA, Pedro R.; AZARBARZIN, Ali; TARANTO-MONTEMURRO, Luigi; MESSINEO, Ludovico; HESS, Lauren B.; DEMKO, Gail; WHITE, David P.; SANDS, Scott A.; WELLMAN, AndrewKey points Some patients with obstructive sleep apnoea (OSA) respond well to oral appliance therapy, whereas others do not for reasons that are unclear. In the present study, we used gold-standard measurements to demonstrate that patients with a posteriorly-located tongue (natural sleep endoscopy) exhibit a preferential improvement in collapsibility (lowered critical closing pressure) with oral appliances. We also show that patients with both posteriorly-located tongue and less severe collapsibility (predicted responder phenotype) exhibit greater improvements in severity of obstructive sleep apnoea (i.e. reduction in event frequency by 83%, in contrast to 48% in predicted non-responders). The present study suggests that the structure and severity of pharyngeal obstruction determine the phenotype of sleep apnoea patients who benefit maximally from oral appliance efficacy. center dot center dot center dot center dot A major limitation to the administration of oral appliance therapy for obstructive sleep apnoea (OSA) is that therapeutic responses remain unpredictable. In the present study, we tested the hypotheses that oral appliance therapy (i) reduces pharyngeal collapsibility preferentially in patients with posteriorly-located tongue and (ii) is most efficacious (reduction in apnoea-hypopnea index; AHI) in patients with a posteriorly-located tongue and less-severe baseline pharyngeal collapsibility. Twenty-five OSA patients underwent upper airway endoscopy during natural sleep to assess tongue position (type I: vallecula entirely visible; type II: vallecula obscured; type III: vallecula and glottis obscured), as well as obstruction as a result of other pharyngeal structures (e.g. epiglottis). Additional sleep studies with and without oral appliance were performed to measure collapsibility (critical closing pressure; Pcrit) and assess treatment efficacy. Overall, oral appliance therapy reduced Pcrit by 3.9 +/- 2.4 cmH(2)O (mean +/- SD) and AHI by 69 +/- 19%. Therapy lowered Pcrit by an additional 2.7 +/- 0.9 cmH(2)O in patients with posteriorly-located tongue (types II and III) compared to those without (type I) (P < 0.008). Posteriorly-located tongue (p = 0.03) and lower collapsibility (p = 0.04) at baseline were significant determinants of (greater-than-average) treatment efficacy. Predicted responders (type II and III and Pcrit < 1 cmH(2)O) exhibited a greater reduction in the AHI (83 +/- 9 vs. 48 +/- 8% baseline, P < 0.001) and a lower treatment AHI (9 +/- 6 vs. 32 +/- 15 events h(-1), P < 0.001) than predicted non-responders. The site and severity of pharyngeal collapse combine to determine oral appliance efficacy. Specifically, patients with a posteriorly-located tongue plus less-severe collapsibility are the strongest candidates for oral appliance therapy.
- Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults(2017) TARANTO-MONTEMURRO, Luigi; SANDS, Scott A.; AZARBARZIN, Ali; MARQUES, Melania; MELO, Camila M. de; EDWARDS, Bradley A.; ECKERT, Danny J.; MESSINEO, Ludovico; WHITE, David P.; WELLMAN, AndrewRationale: The reduction in upper airway muscle activity from wakefulness to sleep plays a key role in the development of obstructive sleep apnea. Potassium (K+) channels have been recently identified as the downstream mechanisms through which hypoglossal motoneuron membrane excitability is reduced both in non-rapid eye movement (NREM) sleep and REM sleep. In animal models, the administration of 4-aminopyridine (4-AP), a voltage-gated K+ channel blocker, increased genioglossus activity during wakefulness and across all sleep stages. Objectives: We tested the hypothesis that administration of a single dose of 4-AP 10 mg extended release would increase genioglossus activity (electromyography of the genioglossus muscle [EMG(GG)]) during wakefulness and sleep, and thereby decrease pharyngeal collapsibility. Methods: We performed a randomized controlled crossover proof-of- concept trial in 10 healthy participants. Participants received active treatment or placebo in randomized order 3 hours before bedtime in the physiology laboratory. Results: EMG(GG) during wakefulness and NREM sleep and upper airway collapsibility measured during NREM sleep were unchanged between placebo and 4-AP nights. Tonic but not phasic EMGGG during REM sleep was higher on the 4-AP night when measured as a percentage of maximal voluntary activation (median [interquartile range] 0.3 [0.5] on placebo vs. 0.8 [1.9] %(max) on 4 AP; P = 0.04), but not when measured in mu V or as a percentage of wakefulness value. Conclusions: A single dose of 4-AP 10 mg extended release showed only a small increase in tonic EMG(GG) during REM sleep in this group of healthy subjects. We speculate that a higher dose of 4-AP may further increase EMG(GG). However, given the potentially severe, dose-related adverse effects of this drug, including seizures, the administration of 4-AP does not appear to be an effective strategy to increase genioglossus activity during sleep in humans.