Thesis (Ph. D.)--University of North Texas, Aug., 2009. / Title from title page display. Includes bibliographical references.

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed Mar. 12, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Medicine, Faculty of Medicine. Degree awarded 2008; thesis submitted 2007. Includes bibliography. Also issued in print.

Master of Science (Medicine) / Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon.

Hypoxia is a common feature of many respiratory disorders including acute severe asthma, chronic obstructive pulmonary disease and pneumonia. Hypoxia also occurs during sleep - disordered breathing in conditions such as sleep hypoventilation syndrome and sleep apnea. In most respiratory diseases hypoxia is coupled with increased respiratory load. Compensatory protective mechanisms are activated to oppose these impediments to respiration. However, hypoxia is associated with impaired neurocognitive function and recent studies have demonstrated that hypoxia suppresses respiratory load perception in healthy individuals and asthma patients. These recent findings raise the possibility that a variety of protective physiological reflex responses to increased respiratory load may be impaired during periods of hypoxia. The effects of hypoxia on several of these protective responses and possible mechanisms of respiratory sensory depression by hypoxia are explored in the experiments outlined in this thesis. In the first study, the respiratory related evoked potential ( RREP ) was used to investigate the mechanisms underlying hypoxia - induced suppression of respiratory load sensation in healthy individuals. As a positive control the effects of hypoxia on respiratory load perception to inspiratory resistive loads were also measured. The amplitude of the first and second positive peaks ( P1 and P2 ) of the RREP were significantly reduced during hypoxia. P1 is thought to reflect the arrival of the ascending respiratory signals to the somatosensory area of the cortex. The perceived magnitude of externally applied inspiratory resistive loads was also reduced during hypoxia. These data provide further support that hypoxia suppresses respiratory load perception and suggest that this is mediated, at least in part, by suppression of respiratory afferent information prior to its arrival at the cortex. In the second study, the effects of acute sustained hypoxia on the cough reflex threshold and cough tachyphylaxis to inhaled capsaicin were explored in healthy individuals. Acute sustained hypoxia suppressed cough reflex sensitivity to inhaled capsaicin. This finding raises the possibility that the cough reflex, important for protecting the lungs from inhalation or aspiration of potentially injurious substances and for clearing excess secretions, may be impaired during acute exacerbations of hypoxic - respiratory disease. In the third study, reflex responses of the genioglossus and scalene muscles to brief pulses of negative airway pressure were compared between hypoxia and normoxia during wake and sleep in healthy males in the supine position. Cortical RREPs to the same stimuli were also examined under these conditions. The genioglossus is the largest upper airway ( UA ) dilator muscle and can be reflexively augmented in response to negative UA pressure. A diminished response of this muscle during sleep has been postulated to be a contributing mechanism to obstructive sleep apnea ( OSA ) in individuals with an anatomically narrow UA. Cortical activation ( i.e. arousal ) to sudden airway narrowing in OSA is an important protective response to help restore ventilation during an obstructive event. In this study, genioglossus reflex responses to negative pressure pulse stimuli were maintained during mild overnight hypoxia. Conversely, reflex inhibition of the scalene muscle to the same stimuli was prolonged during hypoxia. In addition, a previously undescribed morphology of the genioglossus negative pressure reflex consisting of activation followed by suppression was observed with greater suppression during sleep than wake. The amplitude of the P2 component of the RREP was also significantly reduced during hypoxia. In summary, the potential mechanisms underlying hypoxia - induced suppression of respiratory load sensation and the effects of hypoxia on several protective respiratory responses have been investigated in healthy subjects. The potential implications of these findings for patients with hypoxic - respiratory disease are discussed. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2006.

Thesis (Ph. D.)--Case Western Reserve University, 2007. / [School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / School of Physical Education, Sport, and Exercise Science

Master of Science (Medicine) / Clinical studies have demonstrated an arousal deficit in infants suffering Obstructive Sleep Apnoea (OSA), and that treatment to alleviate the symptoms of OSA appears to reverse the deficit in arousability. Some sudden infant deaths are thought to be contingent upon such an arousal deficit. This research utilised young piglets during early postnatal development, and exposed them to intermittent hypercapnic hypoxia (IHH) as a model of clinical respiratory diseases. Arousal responses of control animals were compared to the animals exposed to IHH. Comparisons were also made between successive exposures on the first and the fourth consecutive days of IHH. Time to arouse after the onset of the respiratory stimulus, and frequency of arousals during recovery, demonstrated that arousal deficits arose after successive exposures and that these were further exacerbated on the fourth study day. After an overnight recovery period, the arousal deficit was apparently dormant, and only triggered by HH exposure. These studies confirm that both acute and chronic deficits can be induced on a background of otherwise normal postnatal development, suggesting that deficits observed in the clinical setting may be a secondary phenomenon.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Typescript. Includes bibliographical references (leaves xliii-xlv).