Human pregnancy is characterized by significant increases in central ventilatory drive and perceived respiratory discomfort (breathlessness). The physiological mechanisms of hyperventilation and breathlessness in pregnancy remain largely unknown and understudied. Objective: The main purpose of this research was to elucidate the mechanisms of maternal hyperventilation, and to systematically examine the contribution of alterations in central ventilatory drive, static/dynamic respiratory mechanics and their interaction with respect to the intensity of perceived breathlessness during exercise in pregnancy. General Methods: Experiments were conducted between 34-38 wks gestation and again 4-5 months post-partum in a total of 35 healthy, young women. A comprehensive mathematical model of ventilatory control was used to examine the role of alterations in wakefulness and central chemoreflex drives to breathe, acid-base balance and female sex hormones in maternal hyperventilation. The effects of pregnancy on detailed ventilatory (breathing pattern, airway function, operating lung volumes, esophageal pressure-derived indices of respiratory mechanics) and perceptual (breathing and leg discomfort) responses to incremental cycle exercise to the limits of tolerance were also examined. Results: Maternal hyperventilation resulted from a complex interaction between alterations in arterial and central acid-base balance and other factors that directly affect ventilation, including increased wakefulness and central chemoreflex drives to breathe, increased metabolism and decreased cerebral blood flow. Mechanical adaptations of the respiratory system, including recruitment of resting inspiratory capacity and reduced airway resistance, accommodated the increased demand for tidal volume expansion during exercise in pregnancy, while preserving effort-displacement and breathlessness-ventilation relationships. Variation in the severity of gestational breathlessness could not be explained by respiratory mechanical/muscular factors, but ultimately reflected variation in the amplitude of maternal hyperventilation and temporal desensitization to the sensory consequences of increased ventilation. Conclusion: Our results indicated that 1) the hyperventilation and attendant hypocapnia/alkalosis of pregnancy can be explained by alterations in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow; 2) mechanical adaptations of the respiratory system obviated the anticipated rise in perceived breathlessness for a given ventilation during exercise in pregnancy, and helped to ensure that peak aerobic working capacity was admirably preserved, even in late gestation; and 3) gestational breathlessness ultimately reflected the normal awareness of increased ventilation and contractile respiratory muscle effort. / Thesis (Ph.D, Kinesiology & Health Studies) -- Queen's University, 2008-08-28 16:01:40.78