Sleep Disordered Breathing: Contribution of Abdominal Muscle Activation and Hormonal Intervention in Healthy and Pathological Conditions

• Author / Creator

  Saini, Jasmeen

• Breathing and sleep are both imperative and intricate physiological processes that require development in the perinatal period to sustain life and adapting to changes in postnatal life. Inspiration and expiration are generated by oscillatory microcircuits located in the ventrolateral medulla and work in unison to produce a normal breathing pattern. Inspiratory rhythm is generated by the preBötzinger complex that drives muscle activity of the diaphragm and other inspiratory muscles. The lateral parafacial region drives active expiration through contraction of the abdominal muscles. Respiration is an obligatory ongoing process that may be temporarily interrupted by ongoing behaviours or by apneas that occur in both healthy and pathological conditions.
  Sleep is characterized by different states which are generated and modulated by multiple regions throughout the brain with considerable developmental changes in early postnatal life. The breathing pattern varies with changes in brain states, and this may contribute to the development of sleep disordered breathing. Infants are a particularly impacted population as breathing and sleep are simultaneously undergoing dramatic changes during development and they spend a considerable amount of time sleeping, during which breathing is vulnerable.
  In this thesis I was interested in characterizing the changes postnatal developmental in sleep, breathing parameters and expiratory abdominal activity in rodents. Previous work in our laboratory in adult rodents demonstrated the occurrence of potent expiratory abdominal muscle recruitment mostly during rapid eye movement sleep. Abdominal activation periods in adult rats were more likely to occur after an episode of unstable breathing like an apnea, suggesting that active expiration may be involved in stabilizing breathing when it becomes irregular. Given the ongoing development of the brain and the respiratory system, neonates can be prone to greater respiratory disturbances, so I aimed to investigate if neonatal rodents from postnatal day 0-15 displayed expiratory activity during sleep and how this activation altered respiration. I hypothesized that abdominal activation was associated with a stabilization in ventilation. I instrumented rats with EMG electrodes in respiratory muscles and recorded their behavior to characterize the duration and pattern of sleep states and occurrence of apneas and hypopneas throughout postnatal development, focusing on the activation of abdominal muscles and its relationship to sleep states. Our results suggest that the occurrence of abdominal activation during quiet sleep did not alter respiratory parameters and occurrence decreased with age, whereas active expiration during active sleep was present across development and associated with an increase in minute ventilation and a decrease in respiratory variability across development.
  
  Given our results in infant rodents, I wanted to characterize the pattern of abdominal muscle recruitment in polysomnography recordings obtained from children suspected of sleep disordered breathing. I aimed to investigate whether children also displayed abdominal muscle activation during sleep and how this correlated with respiratory events such as apneas and hypopneas. I hypothesized that activation of the abdominal muscles in human infants occurred during both quiet and active sleep as seen in infant rodents. My results indicated that children also exhibited an expiratory abdominal activation pattern during sleep in both regular sleep and in conjunction with respiratory events, with no specific differences between infants at 0-2 years of age.
  In the last experimental chapter of my thesis, I used a model of impaired central chemoreception to investigate the effects of a potent progestin drug on respiration and chemoreflex responses. A fortuitous study reported a chemoreflex response recovery following implementation of an oral contraceptive etonogestrel, in two female patients affected by congenital central hypoventilation. Here I investigated the hypothesis that etonogestrel would increase ventilation in adult female rodents that were healthy and those with lesions to the retrotrapezoid nucleus, a central chemosensitive region of the brain. My findings indicated that etonogestrel did not affect baseline breathing nor CO2 chemoreflex in healthy female rats. Interestingly, in lesioned rats, respiratory parameters were restored to control levels, indicating a potent stimulatory role of sex hormones on ventilation.
  The final chapter of this thesis is the conclusion which covers the future directions of study on the abdominal activation investigations in mammals, and on the use of etonogestrel as a potential respiratory stimulant in conditions of an impaired chemoreflex. It also addresses the limitations of the present studies that were addressed in subsequent studies in our laboratory.

• Subjects / Keywords

  • Sex Hormones
  • Breathing
  • Sleep
  • Sleep disordered breathing

• Graduation date

  Spring 2024

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-69j4-z909

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.