MELANIA DIRCE OLIVEIRA MARQUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
- 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.
- 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.
- 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.