Grant: Discovery Grants Program - Individual
University of Waterloo
$84,000.00
Physiological mechanisms underlying dynamic cardiorespiratory and cerebrovascular control
EF 2023-24
Résumé
My NSERC-supported research program contributes to the training of exceptional HQP through exploring the complex dynamic physiological adaptations of the cardiorespiratory and cerebrovascular systems to challenges typical of daily life. Our basic research and spaceflight studies have been cited more than 20,000 times and received international awards and national honours. We will continue to develop our influential research on oxygen uptake dynamics by applying artificial intelligence interpretation of wearable sensor data to accurately predict metabolic rate and fitness indicators. Collection of sensor data and "ground-truth" laboratory standards during a 60-day bed rest study in France, and in 9 astronauts before, during and after 6-month spaceflights in our Vascular Aging study will provide HQP rich data sets to mine and explore novel cardiorespiratory indicators related to exercise countermeasures employed during these studies. From our knowledge of regulation of blood flow to working skeletal muscles, we will extend applications of near infrared spectroscopy to monitor changes in perfusion and oxygenation of the tibial bone. My HQP will be the first to study bone perfusion during walking and will explore control mechanisms by manipulating perfusion pressure and vasoconstriction during plantar flexion exercises. We will extend our previous research on cerebral blood flow (CBF) when new trainees are recruited to complete two main projects. The pattern of increase in CBF at the onset of exercise is very poorly described and the mechanisms underlying the increase are incompletely understood. We will apply modeling techniques developed in our study of oxygen uptake kinetics to the increase in CBF. Then we will tease out relative contributions of changes in arterial blood pressure (BP) and CO2 to the increase in CBF by altering arterial CO2 and by regulating breathing patterns, and by manipulating arterial BP. Applying our two-breath method we will determine the gain of the CBF responses to BP and CO2 then predict the change in CBF for comparison to measured CBF to identify regulating factors. During postural tilt, CBF decreases to the point of fainting. This decrease is linked to a fall in arterial BP, but we previously reported that CBF starts to decrease before BP and was related to a drop in arterial CO2, a potent regulator of CBF, yet researchers have argued that fainting is not related to CO2. We see a "chicken and egg" question here, does the drop in CO2 cause a drop in CBF, or does the drop in CBF cause the drop in CO2. We hypothesize the latter and propose experiments in which we manipulate CBF by reducing cardiac output in a random manner to provide time series data that will allow us to apply methods to achieve causal solutions of which occurs first. These results will have a large impact on basic understanding of CBF and could provide important information for many people who experience what are referred to as unexplained falls.
Programme
Discovery Grants Program - Individual
Bénéficiaire
Emplacement
Ontario, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
NSERC's Awards Data
Tel que publié
Application id
RGPIN-2023-03719
Name nom
Hughson, Richard
Department département
Applied Health Sciences
Organization id
33
Institution établissement
University of Waterloo
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2023
Competition year année de concours
2023
Award amount
84000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
DISCOVERY RESEARCH
Group fr
RECHERCHE AXÉE SUR LA DÉCOUVERTE
Committee code
1502
Committee name en
Biological Systems and Functions
Committee name fr
Systèmes et fonctions biologiques
Area of application code
1201
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Life sciences (including biotechnology)
Area of application fr
Sciences de la vie (y compris biotechnologie)
Research subject code
5500
Research subject group en
Animal biology
Research subject group fr
Animal biology
Research subject en
Biologie animale
Research subject fr
Biologie animale
Application title
Physiological mechanisms underlying dynamic cardiorespiratory and cerebrovascular control
Keyword
arterial stiffness; cardiovascular dynamics; cerebrovascular regulation; coded hemodynamic imaging; exercise; human spaceflight; near infrared spectroscopy; oxygen uptake; ultrasound; wearable sensors
Application summary
My NSERC-supported research program contributes to the training of exceptional HQP through exploring the complex dynamic physiological adaptations of the cardiorespiratory and cerebrovascular systems to challenges typical of daily life. Our basic research and spaceflight studies have been cited more than 20,000 times and received international awards and national honours. We will continue to develop our influential research on oxygen uptake dynamics by applying artificial intelligence interpretation of wearable sensor data to accurately predict metabolic rate and fitness indicators. Collection of sensor data and "ground-truth" laboratory standards during a 60-day bed rest study in France, and in 9 astronauts before, during and after 6-month spaceflights in our Vascular Aging study will provide HQP rich data sets to mine and explore novel cardiorespiratory indicators related to exercise countermeasures employed during these studies. From our knowledge of regulation of blood flow to working skeletal muscles, we will extend applications of near infrared spectroscopy to monitor changes in perfusion and oxygenation of the tibial bone. My HQP will be the first to study bone perfusion during walking and will explore control mechanisms by manipulating perfusion pressure and vasoconstriction during plantar flexion exercises. We will extend our previous research on cerebral blood flow (CBF) when new trainees are recruited to complete two main projects. The pattern of increase in CBF at the onset of exercise is very poorly described and the mechanisms underlying the increase are incompletely understood. We will apply modeling techniques developed in our study of oxygen uptake kinetics to the increase in CBF. Then we will tease out relative contributions of changes in arterial blood pressure (BP) and CO2 to the increase in CBF by altering arterial CO2 and by regulating breathing patterns, and by manipulating arterial BP. Applying our two-breath method we will determine the gain of the CBF responses to BP and CO2 then predict the change in CBF for comparison to measured CBF to identify regulating factors. During postural tilt, CBF decreases to the point of fainting. This decrease is linked to a fall in arterial BP, but we previously reported that CBF starts to decrease before BP and was related to a drop in arterial CO2, a potent regulator of CBF, yet researchers have argued that fainting is not related to CO2. We see a "chicken and egg" question here, does the drop in CO2 cause a drop in CBF, or does the drop in CBF cause the drop in CO2. We hypothesize the latter and propose experiments in which we manipulate CBF by reducing cardiac output in a random manner to provide time series data that will allow us to apply methods to achieve causal solutions of which occurs first. These results will have a large impact on basic understanding of CBF and could provide important information for many people who experience what are referred to as unexplained falls.