Current U.S. Veteran demographics reveal an aging population with significant cardiovascular dysfunction. This ultimately manifests as mobility limitation, inactivity, and a subsequent worsening of cardiovascular disease (CVD) that often leads to death. However, despite this clear negative cycle of events, there is not a single clinically accepted, and therefore routinely utilized, method of assessing vascular health. As nitric oxide (NO) is anti- atherogenic and cardioprotective, identifying an in vivo bioassay of NO bioavailability has significant worth in ths arena. Passive leg movement (PLM) and the subsequent blood flow increase, measured non-invasively by ultrasound Doppler in the common femoral artery, is emerging as a method by which vascular endothelial function and therefore NO bioavailability can be determined, however, this method is still in its infancy. Here, we propose the validation and characterization of PLM, as a novel, clinically relevant, method to determine vascular health and guide rehabilitation. With the growing interest in personalized medicine, the development of tools, such as PLM, that allow individualized assessments to guide the physician, the patient, and the rehabilitative team, are essential. Therefore two specific aims are proposed that will address the Central Hypothesis that PLM is an NO-dependent, reproducible, and clinically relevant tool to assess vascular health across the human lifespan. The ultimate goal of the proposed studies will be to assist in catalyzing the transition of the assessment of endothelial function by PLM from research to clinical practice.

Public Health Relevance

Current U.S. Veteran demographics reveal an aging population with significant cardiovascular dysfunction. However, there is not a single clinically accepted, and therefore routinely utilized, method of assessing vascular health. As nitric oxide (NO) is anti-atherogenic and cardioprotective, identifying an in vivo bioassay of NO bioavailability has significant worth in ths arena. Passive leg movement (PLM) and the subsequent blood flow increase, measured non-invasively by ultrasound Doppler in the common femoral artery, is emerging as a method by which vascular endothelial function and therefore NO bioavailability can be determined, however, this method is still in its infancy. Here, we propose the validation and characterization of PLM, as a novel, clinically relevant, method to determine vascular health and guide rehabilitation.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01RX001697-02
Application #
9071359
Study Section
Blank (RRD6)
Project Start
2015-07-01
Project End
2019-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
VA Salt Lake City Healthcare System
Department
Type
DUNS #
009094756
City
Salt Lake City
State
UT
Country
United States
Zip Code
84148
Broxterman, Ryan M; Layec, Gwenael; Hureau, Thomas J et al. (2018) Response. Med Sci Sports Exerc 50:1719
Clifton, Heather L; Machin, Daniel R; Groot, H Jonathan et al. (2018) Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement. Exp Physiol 103:1412-1424
Gifford, Jayson R; Richardson, Russell S (2017) CORP: Ultrasound assessment of vascular function with the passive leg movement technique. J Appl Physiol (1985) 123:1708-1720
Nishiyama, Steven K; Zhao, Jia; Wray, D Walter et al. (2017) Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction. J Appl Physiol (1985) 122:354-360
Broxterman, Ryan M; Layec, Gwenael; Hureau, Thomas J et al. (2017) Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents. Med Sci Sports Exerc 49:2404-2413
Ives, Stephen J; Park, Song Young; Kwon, Oh Sung et al. (2017) TRPV1 channels in human skeletal muscle feed arteries: implications for vascular function. Exp Physiol 102:1245-1258
Machin, Daniel R; Clifton, Heather L; Richardson, Russell S et al. (2017) Acute oral tetrahydrobiopterin administration ameliorates endothelial dysfunction in systemic sclerosis. Clin Exp Rheumatol 35 Suppl 106:167-172
Venturelli, Massimo; Layec, Gwenael; Trinity, Joel et al. (2017) Single passive leg movement-induced hyperemia: a simple vascular function assessment without a chronotropic response. J Appl Physiol (1985) 122:28-37
Broxterman, Ryan M; Trinity, Joel D; Gifford, Jayson R et al. (2017) Single passive leg movement assessment of vascular function: contribution of nitric oxide. J Appl Physiol (1985) 123:1468-1476
Wray, D Walter; Amann, Markus; Richardson, Russell S (2017) Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction. Heart Fail Rev 22:149-166

Showing the most recent 10 out of 24 publications