Blood Pressure Control During Exercise in Heart Failure

描述(由申请人提供)：心功能障碍的一个显著特征是运动耐量降低。即使在正常受试者中，动态运动也是心血管控制面临的最大挑战之一。在大肌群的剧烈动态运动中，为了给活跃的骨骼肌提供足够的血流量和维持动脉血压，心输出量增加，非活动区的血管传导性降低。在心力衰竭的受试者中，由于心脏功能的限制，这些问题变得更加严重，导致心血管对动态运动的反应发生显著变化。在这种情况下，交感神经系统经常发生深刻的激活，表现为高血浆儿茶酚胺和非活跃区域的强烈血管收缩，如内脏和肾血管。即使是活跃的骨骼肌也可能相对收缩血管。人们对这些反应的调节机制知之甚少。在心力衰竭受试者中，存在两种能够引起心血管反应改变的强大反射：肌肉代谢反射和动脉压力反射。这项建议中描述的实验旨在测试肌肉代谢性反射和动脉压力感受性反射在调节心力衰竭时运动引起的心血管反应变化中的功能重要性。使用我们强大的有意识的、慢性仪器化的动物模型，这些研究集中在确定这些反射的中介机制，这些反射之间的相互作用的程度，以及这些机制和相互作用在心力衰竭中是如何改变的。此外，我们还将探讨心力衰竭患者运动时冠脉血流量与心功能的关系，以及心力衰竭恢复后是否能恢复正常的心血管控制机制。

DESCRIPTION (provided by applicant): A hallmark feature of ventricular dysfunction is decreased exercise tolerance. Even in normal subjects, dynamic exercise presents one of the greatest challenges to cardiovascular control. During strenuous dynamic exercise with a large muscle mass, cardiac output increases and vascular conductance to inactive areas decreases in order to provide both sufficient blood flow to active skeletal muscle and to maintain arterial blood pressure. In subjects with heart failure, these problems become exacerbated due to the limitations in ventricular function resulting in markedly altered cardiovascular responses to dynamic exercise. In this setting profound activation of the sympathetic nervous system often occurs as evidenced by high plasma catecholamines and intense vasoconstriction in inactive areas such as the splanchnic and renal vasculatures. Even active skeletal muscle may be relatively vasoconstricted. The mechanisms mediating these responses are poorly understood. 2 powerful reflexes exist which are capable of inducing the altered cardiovascular responses in subjects with heart failure: the muscle metaboreflex and the arterial baroreflex. Experiments described in this proposal are designed to test the functional importance of the muscle metaboreflex and the arterial baroreflex in mediating the altered cardiovascular responses to exercise in heart failure. Using our powerful conscious, chronically instrumented animal model, these studies are focused on determining the mechanisms of mediating these reflexes, the extent of interaction between these reflexes and how these mechanisms and interactions are altered in heart failure. Furthermore, we will explore the relationships between coronary blood flow and ventricular function during exercise in heart failure and whether recovery of normal cardiovascular control mechanisms can occur with the recovery from heart failure.