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Abnormal Vascular, Metabolic, and Neural Function During Exercise in Heart Failure with Preserved Ejection Fraction

射血分数保留的心力衰竭患者运动期间血管、代谢和神经功能异常

基本信息

批准号：
9327726
负责人：
Christopher M Hearon
金额：
$ 5.67万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-15 至 2020-05-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9327726
关键词：
Acetylene Activities of Daily Living Aerobic Blood Vessels Blood flow Cardiac Cardiac Output Clinical EFRAC Educational Intervention Exercise Exercise Tolerance Exercise stress test Extensor Failure Functional disorder Gases Goals Heart failure Human Impairment Ischemia Kinetics Knee Lung Measurement Measures Mediating Metabolic Methodology Morbidity - disease rate Muscle Muscle Contraction Muscle function Nervous system structure Neurophysiology - biologic function Outcome Oxygen Patients Peripheral Population Production Quality of life Reflex action Rest Skeletal Muscle Speed Stress Techniques Testing Training Treatment Efficacy Treatment Failure United States Vasoconstrictor Agents Walking Work afferent nerve design exercise capacity exercise intervention exercise intolerance exercise training experience hemodynamics improved insight mortality muscle form novel patient population peroneal nerve persistent symptom relating to nervous system response targeted treatment uptake vascular abnormality

项目摘要

PROJECT SUMMARY Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the heart failure population in the United States, and the primary chronic symptom experienced by these patients is severe exercise intolerance. Exercise intolerance is quantified as reduced peak oxygen uptake during exercise, and to date, therapies targeting central cardiac limitations have invariably failed to improve peak VO2, quality of life, or survival in HFpEF. Emerging evidence from our lab suggests reduced skeletal muscle oxidative capacity may contribute to exercise intolerance in HFpEF patients. However, the mechanisms responsible for peripheral metabolic inefficiency remain unclear. Reduced blood flow (oxygen delivery), and slowed oxygen uptake kinetics (O2 utilization), may be primary contributors to reduced skeletal muscle oxidative capacity and result in the production of metabolites known to activate muscle afferent nerves and stimulate reflex increases in muscle sympathetic (vasoconstrictor) nervous system activity (MSNA). Elevated MSNA can in turn, result in further impairments in hemodynamic control during exercise. However, to date there have been no studies specifically investigating the contribution of peripheral vascular, metabolic, and neural impairments to reduced exercise capacity in HFpEF. The first goal of this proposal will be to identify impairments in peripheral vascular, metabolic, and sympathetic neural function in HFpEF. To accomplish this, we will measure the dynamic blood flow response (oxygen delivery) and oxygen uptake kinetics (oxygen utilization) during knee extensor (KE) exercise, as well as MSNA during exercise to characterize the contribution of peripheral abnormalities to exercise intolerance in HFpEF. The second goal will be to utilize small muscle mass KE training, specifically targeting these peripheral skeletal muscle deficiencies, to improve aerobic capacity and exercise tolerance in HFpEF. We will assess vascular, metabolic, and neural function before and after completing 8 weeks of single KE exercise training, in conjunction with measures of maximal aerobic capacity and functional capacity. The isolated KE training approach will minimize the central hemodynamic stress of whole body exercise, while simultaneously targeting skeletal muscle function to improve exercise tolerance in HFpEF. Importantly, this proposal will advance our understanding of the basic pathophysiology of exercise intolerance in HFpEF. Considering that vascular function, oxidative capacity, and a MSNA are independent predictors of mortality in heart failure patients, strategies aimed at improving these functional markers may have important implications for the treatment of HFpEF, a condition for which there are currently no known therapies to reduce morbidity and mortality.

项目总结