Journal of applied physiology
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Randomized Controlled Trial
Different antimuscarinics when combined with atomoxetine have differential effects on obstructive sleep apnea severity.
The combination of the noradrenergic agent atomoxetine plus the antimuscarinic oxybutynin has recently been shown to improve upper airway physiology and reduce obstructive sleep apnea (OSA) severity. However, the effects of different antimuscarinics when combined with atomoxetine is limited. This study aimed to determine the effects of atomoxetine combined with two different antimuscarinics with varying M-subtype receptor selectivity on OSA severity and upper airway physiology. ⋯ Atomoxetine + biperiden hydrochloride reduces perceived sleepiness, and atomoxetine + solifenacin modestly improves upper airway function in people with OSA but to a lesser extent versus recently published atomoxetine + oxybutynin (broad M-subtype receptor selectivity) findings. These results provide novel mechanistic insight into the role of noradrenergic and antimuscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA. NEW & NOTEWORTHY In contrast to recent findings of major reductions in OSA severity when atomoxetine is combined with a nonspecific antimuscarinic, oxybutynin (broad M-subtype receptor selectivity), addition of solifenacin succinate (M2 and M3 muscarinic receptor selectivity) or biperiden (M1 muscarinic receptor selectivity) with atomoxetine had modest effects on upper airway function during sleep, which provide mechanistic insight into the role of noradrenergic and antimuscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.
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In the neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS), mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T, should be elevated and VILI is proportional to T. Surfactant therapy is effective in NRDS but not ARDS. ⋯ Given the problematic intratracheal delivery of surfactant therapy for ARDS, intravenous SRB might constitute an alternative therapeutic. In a lung injury model, we find that intravenously administered SRB crosses the injured alveolar-capillary barrier thus reduces T specifically in injured lung regions; improves oxygenation; and reduces the degree of further lung injury. Intravenous SRB administration might help respiratory distress patients, including those with the novel coronavirus, avoid mechanical ventilation or, once ventilated, survive.