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