| Popis: |
Recurrent narrowing and collapse of the upper airway (UA) during sleep is a cardinal feature of Obstructive Sleep Apnoea (OSA). The mechanisms leading to UA narrowing and collapse during sleep are complex. The experimental work described in this thesis focuses on two potential contributing mechanistic factors: (1) End expiratory lung volume (EELV) and (2) upper airway dilator muscle (UADM) function, along with the role played by their interaction in the maintenance of UA patency and the pathophysiology of OSA. This concept is explored through experimental work conducted using both an animal model and human subjects. The interaction between EELV and UADM activity in the pathophysiology of OSA is incompletely understood. This thesis examines the hypothesis that changes in EELV influence the resting length of UADMs, particularly those attached to the chest wall such as the strap muscles of the neck. These include the sternohyoid muscle (SH), the representative UADM chosen for study in this thesis. It is further hypothesised that this change in muscle length will influence both passive and active force generation by the SH through alteration of the operating position of the muscle on its length-tension relationship. This thesis examines the influence of EELV on the active and passive properties of the SH and upper airway resistance (RUA) in a series of animal model studies (anaesthetised rat). Supine dominant obstructive sleep apnoea (SDOSA) is a subtype of OSA characterised by more severe sleep disordered breathing (SDB) in the supine versus lateral posture. There is evidence that a change in EELV between the supine and lateral posture may, at least in part, account for this posture related change in SDB severity. The severity of SDB in patients with SDOSA may therefore be more susceptible to the changes in EELV. This thesis explores the interaction between body posture, EELV and SH muscle activity using head-up bed tilt (HUT) in patients with SDOSA studied during both wakefulness and sleep. |
