Cardiac vs. Peripheral Vascular Dependency of Cardiovascular Circuit Flow in Exercise

随着年龄的增长，积极锻炼身体可以保护我们的生活质量和健康。了解是什么决定了运动耐受性，为实现积极的生活方式提供了关键的指导。因此，我的研究调查了心血管系统如何发挥作用，以满足人类运动肌肉对氧气的需求，因为肌肉疲劳和运动时的不适感限制了运动耐受性，对氧气输送的充分性非常敏感。当前的研究问题：锻炼肌肉有巨大的能力来增加它对氧气的需求。这对心血管系统在维持动脉血压的同时增加循环血流量（心输出量到肌肉血流量到静脉回流到心输出量）的能力提出了相当大的挑战。虽然我们已经了解了很多：1)运动肌肉时扩张血管的机制以达到更高的血流量，2)激活心脏以增加其收缩速度和强度的神经机制，以及3)反对运动肌肉血管扩张的神经机制；这些机制的作用和相互作用的方式被解释为，如果允许增加肌肉血流量超过心输出量，就会对动脉血压构成潜在威胁。它反映了一种循环结构，在这种结构中，心脏的反应决定了心血管循环流量随着运动可以增加的速度和数量。目前的这种解释忽略了越来越多的证据，即心脏会泵出它从运动肌肉中接收到的任何血液，因此除非达到其泵血能力的极限，否则血液流量不会超过心脏。问题：我认为关于心血管循环流动的“心脏受限和驱动”的观点可能是有缺陷的，需要重新审视。本提案的总体目标是：1)挑战目前对运动肌肉血流的交感抑制的解释，2)确定运动中心血管回路血流在多大程度上受到运动肌肉血流与心输出量的驱动/限制。预期结果：挑战目前公认的心血管运动控制观点提供了一个研究环境，在这个环境中，HQP将为创建应用创新思维、实验创造力和不断反思当前公认范式的研究项目制定蓝图。换句话说，发展范式转换研究的能力。其次，证明了心脏驱动心血管循环的外周起源，心脏只是对将体积转移回动脉循环做出反应，从根本上改变了对运动中心血管控制的理解范式。这对于指导有针对性的方法在运动中改善心血管功能具有重要意义，当心血管功能因衰老、不活动或疾病而下降时。

Being physically active protects quality of life and well-being as we age. Understanding what determines exercise tolerance provides key guidance for enabling a physically active lifestyle. Therefore, my research investigates how the cardiovascular system functions to meet exercising muscle demand for oxygen in humans, because fatigue of muscle and feelings of discomfort in exercise that limit exercise tolerance are highly sensitive to the adequacy of oxygen delivery. Current Research Problem: Exercising muscle has a tremendous capacity to increase its demand for oxygen. This poses a considerable challenge to the cardiovascular system's ability to increase the circuit blood flow (cardiac output to muscle blood flow to venous return to cardiac output) while maintaining arterial blood pressure. While much has been learned about 1) mechanisms that dilate blood vessels in exercising muscle to achieve higher blood flow, 2) neural mechanisms that activate the heart to increase the rate and strength of its contractions, and 3) neural mechanisms that oppose exercising muscle blood vessel dilation; the way these mechanisms act and interact has been interpreted from the point of view that increasing muscle blood flow is a potential threat to arterial blood pressure if it is allowed to exceed the cardiac output. It reflects a construct of the circulation where the response of the heart determines how quickly and how much the cardiovascular circuit flow can increase with exercise. This current explanation ignores accumulating evidence that the heart pumps whatever blood flow it receives from exercising muscle and therefore cannot be exceeded by that flow unless the limits of its pumping capacity are reached. The Problem: I propose that the "cardiac-limited and driven" view of cardiovascular circuit flow may be flawed and requires renewed scrutiny.   Overall objectives of this proposal are: 1) to challenge the current explanation for sympathetic restraint of exercising muscle blood flow, 2) to determine the extent to which cardiovascular circuit flow in exercise is driven/limited by exercising muscle blood flow vs. cardiac output. Anticipated Outcomes: Challenging currently accepted views of cardiovascular control in exercise provides a research environment in which HQP's will develop the blueprint for creating research programs that apply innovative thinking, experimental creativity and the willingness to continually rethink currently accepted paradigms. In other words, develop the capacity for paradigm-shifting research. Second, demonstrating a peripheral origin of driving cardiovascular circuit flow with a heart that simply responds to transfer volume back over to the arterial circulation fundamentally changes the paradigm of understanding cardiovascular control in exercise. This has critical implications for guiding targeted approaches to improving cardiovascular function in exercise when it declines due to aging, inactivity or disease.