Grant: Discovery Grants Program - Individual

In healthy humans, respiratory blood gases (PO2 and PCO2) and blood acid-base variables (e.g., pH and bicarbonate) are maintained within narrow ranges, supporting normal function. However, blood gases are challenged by various atmospheric, recreational and occupational contexts, where O2 can be low (hypoxia) and/or CO2 can be low (hypocapnia) or high (hypercapnia), challenging arterial oxygenation and pH, and negatively impacting normal metabolism. The chemoreflex control of breathing and renal acid-base regulation are mediated trough complex coordination and interactions between the lungs, heart, brain, blood and kidneys in order to maintain blood gas and acid-base homeostasis in the face of blood gas challenges. In this independent research program proposal, the integrated coordination between the respiratory and renal systems will be explored in healthy humans across diverse contexts, including laboratory and recreational exposures to acute and chronic blood gas (O2 and CO2) and acid-base challenges (e.g., high altitude ascent) using both well-established and recently-characterized novel, portable, and simple methodologies and analytical methods. Following these novel and systematic investigations into the interrelationships between respiratory and renal systems in healthy humans, a comprehensive and integrative picture of the responses to acute and chronic blood gas and acid-base challenges will emerge. Specifically, this NSE program will fill knowledge gaps in our comprehensive understanding of integrative respiratory-renal functioning, elucidating the phenotypic variability, time-course, bi-directional magnitudes, upper and lower thresholds and oxygen-dependent plasticity of respiratory- and renally-mediated acid-base homeostatic mechanisms in healthy humans. In addition, the continued development of novel methodologies and analytical models will increase our capacity to make meaningful measurements in clinical, laboratory and austere field environments in large groups of individuals. These integrative perspectives will help us better understand normal respiratory-renal functioning in healthy humans exposed to extreme environmental and occupational contexts (e.g., high altitude ascent, confined spaces, long-term space flight), and help develop interventions and countermeasures to mitigate abnormal and maladaptive responses.