Aspects of respiratory physiology and autonomic function after extreme respiratory stress and in brainstem disease

Competitive freedivers repeatedly tolerate physiological extremes of intra-thoracic pressure, lung volume and arterial blood gas tensions - both with alveolar hyperbaria during glossopharyngeal insufflation (GI) at sea level and with extrinsic hyperbaria as they dive. Lung size changes acutely with these pressures and repetitive exposure to this over time may alter lung function and structure. The associated tolerance of severe hypoxia and hypercapnia may affect ventilatory control and cardiac autonomic function. Similarly, abnormal ventilatory and autonomic function may also be a feature of early Parkinson's disease (PD). A recent hypothesis suggests that PD originates in the medulla rather than the midbrain, which may result in central ventilatory effects and disorders of autonomic parameters prior to the classical motor manifestations. The aim of this Thesis was to describe ventilatory function and control in elite freedivers that voluntarily endure the limits of hypoxia and in PD subjects that may have early central ventilatory dysfunction. Importantly, a method was derived to concomitantly measure ventilatory and autonomic responses to differentiate voluntary override of the ventilatory response from intrinsic deficits. Lung volume measurements were collected acutely following repetitive bouts of hyperbaric compression and longitudinally following many years of freediving participation. The respiratory function of patients with moderate and mild PD was measured including respiratory muscle strength. Ventilatory and autonomic responses to progressive hypoxia and hypercapnia were assessed in all study subjects and compared to healthy, non-diving controls. Lung volumes were not affected by repeated intra-day exposure to hyperbaria, however freedivers who perform GI have increased total lung capacity without evidence of reduced lung compliance. This suggests that the increased lung volume is related to reduced chest wall recoil. Freedivers displayed voluntary ventilatory override during the ventilatory control studies, with a normal autonomic response as reflected in pulse transit time and heart rate variability. Subjects with PD had normal lung volumes, with a reduced ventilatory drive in moderate, but not mild disease. However in mild PD, a reduced autonomic response to hypoxia was identified that was not affected by PD dopaminergic therapy. The derived method gave important insight both into subjects that were at the limit of human endurance and in patients with brainstem disease. The concomitant analysis of ventilatory and autonomic function differentiated voluntary override in the freedivers, from subtle intrinsic deficits in patients with mild PD. This analysis has potential for wide application across disease states that are affected by primary or ancillary autonomic dysfunction.