title: Early life exposure to chronic intermittent hypoxia causes upper airway dilator muscle weakness, which persists into young adulthood.
abstract: What is the central question of this study? Chronic intermittent hypoxia (CIH) is a dominant feature of respiratory control disorders, which are common. We sought to examine the effects of exposure to CIH during neonatal development on respiratory muscle form and function in male and female rats. What is the main finding and its importance? Exposure to CIH during neonatal development caused sternohyoid muscle weakness in both sexes; an effect that persisted into young adult life upon return to normoxia. Upper airway dilator muscle dysfunction in vivo could predispose to airway collapse, leading to impaired respiratory homeostasis. Chronic intermittent hypoxia (CIH) is a feature of sleep-disordered breathing, which is very common. Exposure to CIH is associated with aberrant plasticity in the respiratory control system including the final effector organs, the striated muscles of breathing. We reasoned that developmental age and sex are key factors determining the functional response of respiratory muscle to CIH. We tested the hypothesis that exposure to CIH causes persistent impairment of sternohyoid muscle function due to oxidative stress and that males are more susceptible to CIH-induced muscle impairment than females. Wistar rat litters (with respective dams) were exposed to intermittent hypoxia for 12 cycles per hour, 8 h per day for 3 weeks from the first day of life [postnatal day (P) 0]. Sham experiments were run in parallel. Half of each litter was studied on P22; the other half was returned to normoxia and studied on P42. Functional properties of the sternohyoid muscle were determined ex vivo. Exposure to CIH significantly decreased sternohyoid muscle force in both sexes; an effect that persisted into young adult life. Chronic intermittent hypoxia had no effect on sternohyoid muscle endurance. Chronic intermittent hypoxia did not affect sternohyoid myosin fibre type, succinate dehydrogenase or glycerol-3-phosphate dehydrogenase activities, or protein free thiol and carbonyl content. Muscles exposed to CIH had smaller cross-sectional areas, consistent with the observation of muscle weakness. In human infants with disordered breathing, CIH-induced upper airway dilator muscle weakness could increase the propensity for airway narrowing or collapse, which could serve to perpetuate impaired respiratory homeostasis.
authors.affiliation: School of Medicine and Medical Science, Health Sciences Centre, University College Dublin, Dublin, Ireland.
authors.forename: Fiona B
authors.initials: FB
authors.lastname: McDonald
authors.affiliation: Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Williams
authors.affiliation: School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Sheehan
authors.affiliation: School of Medicine and Medical Science, Health Sciences Centre, University College Dublin, Dublin, Ireland.|Department of Physiology, School of Medicine, University College Cork, Cork, Ireland.
authors.forename: Ken D
authors.initials: KD
authors.lastname: O'Halloran
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D005260:Female; D000860:Hypoxia / Q000150:complications* / Q000473:pathology*; D008297:Male; D018908:Muscle Weakness / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012132:Respiratory Muscles / Q000254:growth & development* / Q000473:pathology*