Mechanisms of Phenotypic Variance in Cardiovascular Responses to Exercise

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When people perform physical activity like aerobic exercise, the cardiovascular system matches oxygen delivery to the muscle's oxygen demand. This is the corner stone of sustainable energy production and in the end, governs our capacity to perform and tolerate exercise. The amount of blood the muscle receives depends on the output of blood from the heart and the degree of blood vessel dilation in the active muscle. My recent work has demonstrated profound inter-individual phenotypic differences in how the blood vessels and heart respond to exercise. This phenotypic variability impacts exercise performance due to differences in how well oxygen delivery is matched to the muscle's oxygen demand, yet phenotypic variability is often masked by traditional experimental design of group-level mean data. My research program utilizes a novel experimental approach focusing on unique phenotypic responses in order to explore how well individuals match oxygen delivery to oxygen demand during exercise. The long-term objective of my research program is to identify and understand how inter-individual phenotypic cardiovascular responses impact the ability to match oxygen delivery to oxygen demand during physical exertion. In the present proposal, I am seeking to: 1) Determine the contribution of red blood cell desaturation to inter-individual differences in how our blood vessels dilate during exercise; 2) Determine the extent to which left ventricular structure and function contribute to inter-individual differences in output from the heart during exercise; and 3) Explore the application of statistical models to identify potential unique phenotypic signatures that predict an individual's acute cardiovascular response to exercise. For the research community, this research program will, for the first time, attempt to identify and unmask the mechanisms explaining inter-individual phenotypic variability in how the blood vessels and heart respond to exercise and will advance our understanding about how and why individualized strategies and outcomes exist when examining acute responses and chronic adaptations to exercise. This information may represent a critical missing link in understanding cardiovascular control, the individual capacity for exercise performance and the responsiveness to exercise training, and the vulnerability to exertional intolerance. The findings from this basic mechanistic research may be leveraged to identify personalized oxygen delivery pathways, which can have a tremendous application in not only human performance and exercise training, but can inform strategies of targeted, personalized or `precision' interventions, similar to the emerging field of personalized medicine. A key outcome would be to improve exertional tolerance, a known limitation across performance and rehabilitation spectrums. The proposed research will provide the foundational knowledge required to begin utilizing this information to improve the lives of Canadians.