Project 1: The Muscle Reflex: Modes of Engagement and Circulatory Consequences

项目摘要/摘要--项目1 在过去的资金支持期间，我们证明了足底屈曲运动引起的血压升高 与健康受试者相比，外周动脉疾病受试者(PFE)增加。这个BP 反应是由于受试者在低工作负荷时出现的运动加压反射(EPR)加重 出现腿部疼痛。我们还证明，静注酮咯酸和非酮洛酸都能减弱EPR。 类固醇抗炎药[非甾体抗炎药()]和大剂量静脉注射抗坏血酸，短期有效 抗氧化剂(62)在健康的受试者中，这些药物没有效果。因此，花生四烯酸的两种代谢物 氧化应激参与了PAD的EPR。在这次更新中，我们建议进行港口及机场发展策略研究，以研究 EPR参与对有症状的肢体和心脏的循环的影响。我们有 开发了新的方法、范例和干预措施，并收集了试点数据，表明我们的 假设是正确的，实验是可行的。 目的1：我们将研究EPR如何影响PAD患者运动腿的血流和氧合。 和健康的受试者。 1A.PAD和健康受试者对运动的股动脉和月国动脉血流反应是否不同？ 1B.PAD和健康受试者对运动的大胆SI反应是否不同？ 1C。药物干预是否能改善PAD运动后的血流和氧合反应？ 1D.腿部血运重建是否能改善腿部血流量和对运动的氧合反应？ 目的2：我们将研究EPR如何影响PAD患者静息时的血流和氧合。 和健康的受试者。 2a.与健康受试者相比，EPR是否增强了PAD患者静息状态下的腿部血管收缩？ 2B。在PAD和健康受试者之间，静息状态下腿部的大胆SI反应是否不同？ 2C。药物干预是否能改善静息状态下PAD的腿部血流和氧合？ 2D。小腿血运重建术是否能改善静息状态下的小腿血流量和PAD的氧合？ 目的3：我们将研究EPR如何影响PAD患者的冠脉血流量和左心功能。 和健康的受试者。 3A。PAD和健康受试者对运动的冠脉血流反应是否不同？ 3B。PAD和健康受试者对运动的左心室反应是否不同？ 3C。药物干预是否能改善PAD患者的冠脉血流量和左心功能？ 3D。小腿血运重建术是否能改善PAD运动期间的冠脉血流量？ 综上所述，AIMS 1、2和3使用无创的尖端方法来了解PAD患者的EPR。

PROJECT SUMMARY/ABSTRACT – PROJECT 1 Over the last funding period, we demonstrated that the rise in blood pressure (BP) with plantar flexion exercise (PFE) is increased in subjects with peripheral arterial disease (PAD) as compared to healthy subjects. This BP response was due to an accentuated exercise pressor reflex (EPR) seen at low workloads, before subjects developed leg pain. We also demonstrated that the EPR is attenuated by both intravenous ketorolac, a non- steroidal anti-inflammatory drug [NSAID (64)] and high dose intravenous ascorbic acid, an effective short-term antioxidant (62). In healthy subjects, these agents had no effect. Thus, both metabolites of arachidonic acid and oxidative stress contribute to the EPR in PAD. In this renewal, we propose PAD studies examining the consequences of EPR engagement on the circulation to the symptomatic limb and the heart. We have developed new methods, paradigms, and interventions and have collected pilot data demonstrating that our hypotheses are valid and the experiments are feasible. AIM 1: We will examine how the EPR affects blood flow and oxygenation in the exercising leg of PAD patients and healthy subjects. 1A. Are femoral and popliteal blood flow responses to exercise different between PAD and healthy subjects? 1B. Are BOLD SI responses to exercise different between PAD and healthy subjects? 1C. Do pharmacological interventions improve blood flow and oxygenation responses to exercise in PAD? 1D. Does leg revascularization improve leg blood flow and oxygenation responses to exercise? AIM 2: We will examine how the EPR affects blood flow and oxygenation in the resting leg of PAD patients and healthy subjects. 2A. Does the EPR enhance resting leg vasoconstriction in PAD vs. healthy subjects? 2B. Are BOLD SI responses in the resting leg different between PAD and healthy subjects? 2C. Do pharmacological interventions improve resting leg blood flow and oxygenation in PAD? 2D. Does leg revascularization improve resting leg blood flow and oxygenation in PAD? AIM 3: We will examine how the EPR affects coronary blood flow and left ventricular function in PAD patients and healthy subjects. 3A. Is the coronary blood flow response to exercise different between PAD and healthy subjects? 3B. Are left ventricular responses to exercise different between PAD and healthy subjects? 3C. Do pharmacological interventions improve coronary blood flow and left ventricular function in PAD? 3D. Does leg revascularization improve coronary blood flow during exercise in PAD? In summary, Aims 1, 2 and 3 use non-invasive cutting-edge methods to understand the EPR in PAD patients.