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

项目 1：肌肉反射：参与模式和循环系统后果

• 批准号: 10117110
• 负责人: Lawrence I Sinoway
• 金额: $ 78.19万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117110
• 关键词: 3-Dimensional; Acute; Affect; Amputation; Antioxidants; Arachidonic Acids; Arteries; Ascorbic Acid; Attenuated; Blood Circulation; Blood Pressure; Blood flow; Chronic; Coronary; Data; Disease; Doppler Ultrasound; Dose; Exercise; Funding; Gastrocnemius Muscle; Heart; Impairment; Infusion procedures; Intervention; Intravenous; Ketorolac; Left; Left Ventricular Function; Leg; Life; Limb structure; Medial; Methods; Muscle; Myocardial; Myocardial Infarction; Non-Steroidal Anti-Inflammatory Agents; Organ; Oxidative Stress; Oxygen; Pain; Pain in lower limb; Patients; Peripheral arterial disease; Pharmacology; Play; Process; Reflex action; Rest; Role; Skeletal Muscle; Stroke; Structure of popliteal artery; Vascular Diseases; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Ventricular; Work; Workload; acid stress; base; disabling disease; experimental study; heart metabolism; high risk; improved; prevent; response; tool; vasoconstriction

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.

项目摘要/摘要 – 项目 1 在上一个资助期间，我们证明了跖屈运动会导致血压（BP）升高 与健康受试者相比，患有外周动脉疾病（PAD）的受试者（PFE）增加。这个BP 反应是由于受试者在低负荷时出现了强烈的运动加压反射（EPR） 出现腿部疼痛。我们还证明，静脉注射酮咯酸（一种非酮咯酸）可减弱 EPR。 类固醇抗炎药 [NSAID (64)] 和高剂量静脉注射抗坏血酸，是短期有效的 抗氧化剂（62）。在健康受试者中，这些药物没有效果。因此，花生四烯酸的两种代谢物 氧化应激有助于 PAD 中的 EPR。在本次更新中，我们建议进行 PAD 研究，检查 EPR 参与对有症状的肢体和心脏循环的影响。我们有 开发了新的方法、范式和干预措施，并收集了试点数据，表明我们的 假设成立，实验可行。 目标 1：我们将研究 EPR 如何影响 PAD 患者运动腿的血流和氧合 和健康受试者。 1A。 PAD 和健康受试者的股骨和腘动脉血流对运动的反应是否不同？ 1B. PAD 和健康受试者之间的 BOLD SI 对运动的反应是否不同？ 1C.药物干预是否可以改善 PAD 患者的血流量和运动氧合反应？ 1D。腿部血运重建能否改善腿部血流量和运动时的氧合反应？ 目标 2：我们将研究 EPR 如何影响 PAD 患者静息腿的血流和氧合 和健康受试者。 2A。与健康受试者相比，EPR 是否能增强 PAD 患者的静息腿部血管收缩？ 2B。 PAD 和健康受试者静息腿的 BOLD SI 反应是否不同？ 2C。药物干预是否可以改善 PAD 患者的静息腿部血流和氧合？ 2D。腿部血运重建能否改善 PAD 患者的静息腿部血流和氧合？ 目标 3：我们将研究 EPR 如何影响 PAD 患者的冠状动脉血流和左心室功能 和健康受试者。 3A。 PAD 和健康受试者的冠状动脉血流对运动的反应是否不同？ 3B. PAD 和健康受试者的左心室对运动的反应是否不同？ 3C。药物干预能否改善 PAD 患者的冠状动脉血流和左心室功能？ 3D。腿部血运重建能否改善 PAD 运动期间的冠状动脉血流量？ 总之，目标 1、2 和 3 使用非侵入性尖端方法来了解 PAD 患者的 EPR。