Mechanisms of Phenotypic Variance in Cardiovascular Responses to Exercise

当人们进行有氧运动等体力活动时，心血管系统会将氧气输送与肌肉的需氧量相匹配。这是可持续能源生产的基石，最终决定了我们进行和容忍锻炼的能力。肌肉接受的血量取决于心脏的输血量和活跃肌肉中血管的扩张程度。我最近的工作表明，在血管和心脏对运动的反应方式上，个体之间存在着深刻的表型差异。由于氧气输送与肌肉需氧量的匹配程度不同，这种表型变异性会影响运动成绩，但表型变异性往往被组级平均数据的传统实验设计所掩盖。我的研究项目使用了一种新的实验方法，专注于独特的表型反应，以探索个人在运动过程中如何将氧气输送与氧气需求很好地匹配。我的研究计划的长期目标是确定和了解个体间表型心血管反应如何影响体力消耗时氧气输送与氧气需求的匹配能力。在目前的建议中，我试图：1)确定红细胞减饱和对运动中血管扩张方式的个体间差异的贡献；2)确定运动中左室结构和功能对心脏输出量的个体间差异的影响程度；3)探索统计模型的应用，以确定预测个人对运动的急性心血管反应的潜在独特表型特征。对于研究界来说，这项研究计划将首次尝试识别和揭示解释心血管和心脏对运动反应的个体间表型差异的机制，并将促进我们对如何以及为什么在检查运动的急性反应和慢性适应时存在个性化的策略和结果的理解。这些信息可能代表了在理解心血管控制、个人运动能力和运动训练反应能力以及对劳力不耐受的脆弱性方面的关键缺失环节。这一基础机制研究的结果可能被用来确定个性化的氧气输送途径，这不仅可以在人类表现和运动训练中有巨大的应用，而且可以为有针对性的、个性化的或“精确”干预的战略提供信息，类似于新兴的个性化医学领域。一个关键的结果将是提高运动耐力，这是一个已知的跨运动和康复光谱的限制。拟议的研究将提供开始利用这些信息改善加拿大人生活所需的基础知识。

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.