Blood Flow and Blood Pressure Investigation in Down Syndrome

Specific Aims

Down Syndrome (DS) is the most prevalent genetic form of intellectual disability, and individuals with DS have low work capacity. Reduced work capacity limits gross motor function, and thus, reduces independence, full participation, and ultimately quality of life (QOL). Low work capacity is associated with central autonomic dysfunction in persons with DS, which limits maximal heart rates ~30 beats below expected values. However, during exercise, the autonomic nervous system also balances peripheral blood flow delivery and blood pressure regulation, through the redistribution of blood to active skeletal muscle. Blood flow redistribution occurs primarily through sympathetically-mediated changes in vasomotor tone by stimulation of mechanically and metabolically sensitive afferent fibers in the skeletal muscle, which results in changes in pressure to maintain adequate flow. It is unknown whether the observed central autonomic dysfunction in individuals with DS also alters peripheral blood flow regulation or the blood pressure response to lower limb exercise, which is critical to improving work capacity and ultimately participation and QOL.

Blood flow redistribution occurs in an intensity-dependent manner regulated through changes in pressure, away from inactive tissue towards exercising or active muscle through vasoconstrictive mechanisms. Data from our lab using a mild sympathetic stimulus, namely lower body negative pressure, suggests individuals with DS have reduced vasoconstrictive control. Reduced ability to vasoconstrict inactive tissue during exercise may inhibit appropriate distribution of blood flow to active muscle, which may be particularly limiting during large muscle exercise, thereby limiting work capacity. In addition to reduced vasoconstrictive control, blood flow during exercise is driven by sympathetically-mediated increases in blood pressure from muscular contraction activating the mechano- and metaboreflexes, termed the exercise pressor reflex. Individuals with DS have a blunted blood pressure response to sympathoexcitatory challenges, such as isometric handgrip exercise, suggesting impairments in blood pressure regulation. Taken together, our previous work (i.e., preliminary data) suggests that the redistribution of blood flow and blood pressure regulation may be impaired during stimuli involving small muscle mass for individuals with DS. However, blood flow and blood pressure regulation have not been examined using large muscle exercise (e.g., lower limb exercise) in DS, which may be a more impactful and limiting factor for individuals with DS in regards to work capacity.

Active, lower limb exercise requires greater peripheral blood flow regulation to ensure a match between oxygen demand and supply, which is critical to improving blood pressure regulation and thus, work capacity. The aim of this study is to comprehensively evaluate blood flow redistribution by examining blood flow to active and non-active legs during dynamic (rhythmic muscular activity) lower limb exercise with increasing exercise intensity. In contrast, isometric (contraction of muscles without movement in surrounding joints) lower limb exercise will allow for investigation of blood pressure regulation in individuals with DS through activation of the exercise pressor reflex. More specifically, the metaboreflex can be assessed with post-exercise ischemia that traps metabolites in a regional area, wherein blood pressure and sympathetic activity remain elevated, independent of cardiac output. Interestingly, neither blood flow redistribution nor the exercise pressor response to large muscle exercise have been previously explored in individuals with DS. Investigation of these mechanisms will help elucidate the mechanisms of low work capacity, ultimately leading to improved health outcomes, participation, and QOL for individuals with DS.

The overall aim of this study is to comprehensively evaluate blood flow regulation, including the pressor reflex, in two research aims: Aim 1 (Dynamic Exercise): To examine the effects of lower limb dynamic exercise on femoral blood flow in both exercising and non-exercising legs in individuals with and without DS. The investigators hypothesize individuals with DS will have: a) attenuated femoral blood flow to the active leg at all intensity workloads of dynamic exercise and b) a lack of blood flow control as demonstrated by a lack of vasoconstriction in the non-exercising leg compared to individuals without DS. Aim 2 (Isometric Exercise): To examine the effects of lower limb isometric exercise on the exercise pressor response in individuals with and without DS. The investigators hypothesize the individuals with DS will exhibit an attenuated blood pressure response, demonstrating dysfunction of the exercise pressor reflex following isometric single-leg extension.