Intermittent Hypoxia and Cardiopulmonary Adaptation

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The cardiovascular, respiratory and autonomic nervous systems interact to maintain a relative homeostasis during physiological stressors (e.g., exercise, heat, hypoxia). The human body's ability to adapt when exposed to low levels of oxygen (called hypoxia) highlights an important multi-system coordination of physiological responses. The integrated study of these systems provides insight into their adaptation to hypoxia and contributes to our comprehensive understanding of basic human physiology. The long-term objective of my research program is to understand how the respiratory, cardiovascular, and autonomic nervous systems interact, respond, and adapt to hypoxia. **Important differences in the cardiopulmonary systems response to hypoxia of varying intensity, duration, and repetition [i.e. intermittent hypoxia (IH)] have been identified yet our understanding of the mechanisms controlling these differences is poorly understood. Cardiopulmonary adaptation to IH is of particular interest in light of the growing use of IH training with athletes (e.g., hockey, Olympics, mountain climbers). As Canada continues to remain strong at competitive sports, it is prudent to fully explore the basic physiological mechanisms behind the adaptations that take place when healthy humans are exposed to hypoxia. **The research program is divided into two research themes with specific research objectives. In theme I, a series of studies will be aimed at understanding the relationship between sympathetic nerve activity, vascular diameter, and blood flow during and following exposure to hypoxia. Exposure to IH in animals and humans leads to increases in chemoreceptor sensitivity, sympathetic activity, arterial blood pressure, and oxidative stress. The specific mechanisms responsible for these adaptations to IH are unknown; however, our preliminary investigations suggest signaling through the renin-angiotensin system might be involved. Two research objectives have been identified: (1) to determine the differential effect of sustained versus IH on neurovascular coupling in the peripheral and cerebral circulations; and (2) to determine the involvement of the renin-angiotensin system in potentiating sympathoexcitation following IH. In theme II, a series of studies will be aimed at identifying how hypoxia leads to the opening of intrapulmonary arteriovenous anastomoses (IPAVA). IPAVA are pulmonary vessels that bypass the gas exchange surface of the lung and thereby decrease oxygen delivery. This research theme will identify a potential role for IPAVA in protecting pulmonary capillaries from high perfusion pressures that occur during hypoxia. In addition, it will develop a new image analysis tool for quantifying blood flow through IPAVA and determine the humoral and mechanical stimuli responsible for opening and closing IPAVA during hypoxia. For theme II, two research objectives have been identified: (1) to develop and validate a quantitative analysis tool for measuring blood flow through IPAVA from agitated saline contrast echocardiograms; and (2) to determine the relative importance of arterial hypoxia versus increased pulmonary artery pressure in mediating the opening of IPAVA during acute hypoxia. **The proposed research program is a logical extension and incorporates new technologies and discoveries made during my NSERC postdoctoral fellowship. All HQP will receive leadership and project management training, develop independent intellectual research capacity, collaborate with associated laboratories, and will drive the development of new methodologies and innovation. Also, HQP will be involved in writing and publishing their results in high impact physiology journals and conference presentations.