Central & Peripheral blood flow regulation in individuals with Down syndrome

唐氏综合征(DS)是导致智力残疾的最常见的遗传原因，发生在 在美国，大约每700个新生儿中就有一个。患有DS的个体患上许多 健康问题。工作能力是健康或身体机能下降的重要预测指标， 死亡率，通常以最大耗氧量来衡量。峰值耗氧量非常大 患有DS的人低，不能用缺乏运动、缺乏动力或缺乏运动来解释 对测试的理解。到目前为止，DS工作能力限制的性质尚不清楚，而且 拟议的研究旨在解决这一知识鸿沟。 作功能力由血液流动的中枢和外周调节(即心输出量和 维持动脉血压与为运动肌肉提供氧气和营养)。这些 因子由自主神经的交感和副交感神经分支控制。 系统。心血管疾病DS患者的血流中枢调节功能受损 自主神经功能障碍，副交感神经活性高，交感神经控制能力降低。这 导致心率减慢，血压控制不力，儿茶酚胺水平降低 在锻炼的时候。目前尚不清楚这种中枢控制受损对心输出量的影响程度，以及 随后，在DS患者的运动过程中，工作能力。 对于DS患者的外周血流调节的研究更少。外围设备监管涉及 交感神经调节的非活动肌肉和组织的血管收缩及其局部机制 调节工作肌肉的血管扩张，促进血液流向工作肌肉，以满足 代谢需求。患有DS的人可能会因此而部分地感受到工作能力的降低 有效地将血液分流到工作组织。 因此，这项研究建议的目的是确定中央和中部地区限制的影响 DS患者外周血流调节对工作能力的影响。我们的目标是研究 对运动训练的反应，以更好地了解潜在的机制和潜在的 通过在运动干预中使用这些知识来改善健康。

Down syndrome (DS) is the most prevalent genetic cause of intellectual disability and occurs in approximately 1 in every 700 births in the US. Individuals with DS are at increased risk for a number of health issues. Work capacity is an important predictor of declining health or physical function, and of mortality, and is commonly measured as peak oxygen consumption. Peak oxygen consumption is very low in individuals with DS, and cannot be explained by physical inactivity, lack of motivation, or lack of understanding of the test. To date, the nature of the limitations in work capacity in DS is unknown, and the proposed research aims to address this knowledge gap. Work capacity is determined by central and peripheral regulation of blood flow (i.e. cardiac output and maintaining arterial blood pressure vs. supplying exercising muscles with oxygen and nutrients). These factors are governed by the sympathetic and parasympathetic branches of the autonomic nervous system. Central regulation of blood flow is impaired in individuals with DS due to cardiovascular autonomic dysfunction, whereby parasympathetic activity is high and sympathetic control is reduced. This results in lower heart rate, less adequate blood pressure control and attenuated catecholamine levels during exercise. It is unknown to what extent this impaired central control impacts cardiac output, and subsequently work capacity, during exercise in individuals with DS. Peripheral blood flow regulation is even less studied in individuals with DS. Peripheral regulation involves sympathetically regulated vasoconstriction in non-active muscles and tissues, and local mechanisms regulating vasodilation in working muscles, which facilitates blood flow to working muscle in order to meet metabolic demand. Individuals with DS may partly experience reduced work capacity due to this inability to shunt blood to the working tissue effectively. The aim of this research proposal is therefore to determine the impact of limitations in central and peripheral regulation of blood flow on work capacity in individuals with DS. We aim to examine the responses to exercise training to better understand the underlying mechanisms and the potential to improve health by using this knowledge in exercise interventions.