Ryan S Garten

• Ph.D.
• Professor (Associate) at Virginia Commonwealth University

Purpose: Chronic anxiety is commonly associated with poor sleep patterns, which may contribute to an increased risk of cardiovascular disease (CVD) through mechanisms like oxidative stress, vascular dysfunction, and poor blood pressure control. As sleep disturbances, particularly poor sleep quality and/or regularity, have been independently linked...

Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) is not fully understood. This study tested the hypothesis that elevated MSNA dim...

Background: Electronic nicotine delivery systems, often referred to as e-cigarettes, are popular tobacco products frequently advertised as safer alternatives to traditional cigarettes despite preliminary data suggesting a potential negative cardiovascular impact. Cardiorespiratory fitness is a critical cardiovascular health marker that is diminish...

Young individuals with post‐traumatic stress disorder (PTSD) display peripheral vascular and autonomic nervous system dysfunction, two factors potentially stemming from a redox imbalance. It is currently unclear if these aforementioned factors, observed at rest, alter peripheral haemodynamic responses to exercise in this population. This study exam...

Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) has not been adequately addressed. This study sought to test the hypothesis that...

Background: Adverse childhood experiences (ACEs) are strong emotional or physical stressors that occur during sensitive developmental periods and are associated with reduced cardiovascular health (CVH). Resilience, or the psychological capacity of individuals to cope with adversity, has been recently shown to have a positive influence on CVH. Despi...

Background Electronic (e-) cigarettes are increasingly popular tobacco products on the US market. Traditional tobacco products are known to cause vascular dysfunction, one of the earliest indicators of cardiovascular disease (CVD) development. However, little is known about the effect of regular e-cigarette use on vascular function. The purpose of...

Objectives: Cardiorespiratory fitness (CRF) is influenced by body composition quantity and quality in heart failure with preserved ejection fraction (HFpEF) and obesity. Bioelectrical impedance analysis (BIA) provides a noninvasive quantitative and qualitative body composition assessment. The aim of this study was to determine the role of phase an...

BACKGROUND: Microvascular dysfunction is a marker of endothelial vascular damage and is considered one of the earliest indicators of cardiovascular disease (CVD) development. Frequent cannabis use has been previously linked to increased CVD risk. However, whether microvascular health is impacted by cannabis use in otherwise healthy young adults has...

BACKGROUND: Electronic cigarettes (e-cigs) are popular tobacco products that are currently advertised as a safer alternative to traditional cigarettes. Preliminary data, primarily from animal studies, suggests that e-cigs are associated with an increased cardiovascular disease (CVD) risk. Cardiorespiratory fitness is a marker of cardiovascular (CV)...

Purpose: Adequate, robust vascular responses to passive and active movement represent two distinct components linked to normal, healthy cardiovascular function. Currently, limited research exists determining if these vascular responses are altered in premenopausal females (PMF) when compared across sex or menstrual cycle phase. Methods: Vascular...

Purpose: This study sought to determine if high sodium (HS) intake in salt resistant (SR) individuals attenuates upper limb arterial dilation in response to reactive (occlusion) and active (exercise) hyperemia, two stimuli with varying vasodilatory mechanisms, and the role of oxidative stress in this response. Methods: Ten young, SR participants...

Simple Summary Lifestyle modifications such as diet and exercise are a first-line defense to promote health in individuals with obesity. High-intensity interval exercise has recently gained popularity as a time-effective exercise modality. As such, this work compared the acute exercise induced benefits on vascular health between high-intensity inte...

Purpose Young non-Hispanic black (BL) males have displayed lower blood flow (BF) and vascular conductance (VC), but intact functional sympatholysis, during upper limb exercise when compared to non-Hispanic white (WH) males. This study sought to explore if similar differences were also present in the lower limbs. Methods Thirteen young BL males and...

Purpose: Vascular responses to passive movement represent a novel assessment of vascular function and serves as a critical component for adequate blood flow regulation during exercise. Although alterations to estradiol (E2) throughout the menstrual cycle, as well as sex differences, are known to impact vascular function, limited research exists in...

Objective: This study sought to determine if a high sodium (HS) intake attenuates upper limb flow mediated dilation in response to reactive (RH-FMD) and sustained (SS-FMD) hyperemia, and the role of oxidative stress in this response. Our hypothesis is HS intake will similarly impair upper limb vascular function when assessed as both RH-FMD and SS-...

Generalized anxiety disorder (GAD) is a disabling psychiatric condition that can result in physiological manifestations linked to a greater risk for cardiovascular disease (CVD). Peripheral vascular dysfunction may be one mechanism augmenting CVD risk as GAD is linked to an overactivation of the sympathetic nervous system, a phenomenon that can res...

New findings: What is the central question of this study? Use of the passive leg movement (PLM) test, a non-invasive assessment of microvascular function, is on the rise. However, PLM reliability in men has not been adequately investigated, nor has such reliability data, in men, been compared to the most commonly employed vascular function assessm...

Background Mitochondrial health is an important predictor of several health-related comorbidities including obesity, type 2 diabetes mellitus, and cardiovascular disease. In persons with spinal cord injury (SCI), mitochondrial health has been linked to several important body composition and metabolic parameters. However, the complex interplay of ho...

As a deficiency in tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase, has been implicated in the age-related decline in vascular function, this study aimed to determine the impact of acute BH4 supplementation on flow-mediated vasodilation (FMD) in old adults. Two approaches were employed: 1) A multi-day, double-blind, plac...

Background Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventri...

Cardiorespiratory fitness (CRF) is a robust and independent predictor of cardiovascular health and overall mortality. Patients with lung cancer often have chronic lung disease, contributing to impaired CRF. Radiation to the heart during lung cancer treatment may further reduce CRF. The determinants of CRF in this population are not well understood....

Purpose: Posttraumatic stress disorder (PTSD) has been associated with an increase in risk of cardiovascular disease (CVD). The goal of the study was to determine if peripheral vascular dysfunction, a precursor to CVD, was present in young adults with PTSD, and if an acute antioxidant (AO) supplementation could modify this potential PTSD-induced v...

A correction to this paper has been published: https://doi.org/10.1007/s00421-021-04701-9

Purpose Lower limb microvascular dysfunction resulting from prolonged sitting (PS) bouts has been revealed to occur independent of sex. Although acute antioxidant supplementation has been reported to blunt conduit artery dysfunction following PS in young males, it is unknown if this protective effect extends to the microvasculature or is relevant i...

Cardiorespiratory fitness (CRF) is a robust and independent predictor of cardiovascular health and overall mortality. Patients with lung cancer often have chronic lung disease, contributing to impaired CRF. Radiation to the heart during treatment of lung cancer may further reduce CRF. The determinants of reduced CRF in this population are not well...

Purpose Pentraxin 3 (PTX3) has been shown to be a predictor of endothelial dysfunction in patients with increased risk of cardiovascular disease (CVD) (e.g., obesity). Circulating PTX3 concentrations are dysregulated in obese individuals and are elevated following acute aerobic exercise. High-intensity interval exercise (HIIE) has been demonstrated...

Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intoleran...

This review discusses the associations of muscular strength (MusS) with cardiovascular disease (CVD), CVD-related death, and all-cause mortality, as well as CVD risk factors, such as metabolic syndrome, diabetes, obesity, and hypertension. We then briefly review the role of resistance exercise training in modulating CVD risk factors and incident CV...

Purpose: Recently, it has been shown that young African American males display lower hyperemic responses, but preserved shear-induced dilation, in response to dynamic handgrip exercise when compared to Caucasian American counterparts; however, it is unknown whether this blunted exercise hyperemia is also present in the lower limbs. Methods: Young A...

PURPOSE: Dietary sodium intake guidelines is ≤2,300 mg/day, yet is exceeded by 90% of Americans. This study examined the impact of a high sodium diet on blood flow regulation during exercise. METHODS: Six males (25 ± 2 years) consumed dietary sodium intake guidelines for two weeks, with one week salt-capsule supplemented (HS: 6,900 mg/day of sodium...

New findings: What is the central question of this study? This study sought to investigate if young adults reporting low sleep quality possessed lower vascular function and altered autonomic nervous system modulation when compared to young adults reporting high sleep quality. What is the main finding and its importance? The study revealed that in...

Chronic obstructive pulmonary disease (COPD), characterized by pulmonary dysfunction, is now also recognized to be associated with free radical-mediated vascular dysfunction. However, as previous investigations have utilized the brachial artery flow-mediated dilation technique, whether such vascular dysfunction exists in the locomotor muscle of pat...

Purpose The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. The goal of the study was to better elucidate the mechanisms behind the increased CVD risk by examining peripheral vascular function, a precursor to...

Purpose This study sought to determine whether fluctuations in estrogen levels throughout the menstrual cycle (early (EF) vs late follicular (EF) phase) altered the vascular and blood flow responses to acute upper limb exercise and if these responses were different when compared to males. Methods Ten young females (YF: 21±3 yrs) were recruited and...

Disturbed sleep, defined as any alteration to normal sleep patterns, has been linked to poor cardiovascular health and an increase in cardiovascular disease (CVD) risk. These negative sleep patterns are highly prevalent with 35% to 41% of individuals in the United States reported some form of disturbed sleep. Although high amounts of physical activ...

Tetrahydrobiopterin (BH 4 ) is a cofactor which recouples eNOS, potentially increasing nitric oxide (NO)‐bioavailability. Previously, BH 4 has been documented to restore conduit artery vascular dysfunction, assessed by flow mediated vasodilation (FMD) in sedentary old subjects. This study aimed to determine if BH 4 can restore microvascular functio...

Background: Irradiation of the heart during cancer radiotherapy is associated with a dose-dependent risk of heart failure. Animal studies have demonstrated that irradiation leads to an inflammatory response within the heart as well as a reduction in cardiac reserve. In the current study we aimed to evaluate whether inflammatory biomarkers correlat...

We measured peak oxygen consumption (VO2) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as...

Background: This study sought to determine the impact of an acute prior bout of high-intensity interval aerobic exercise on attenuating the vascular dysfunction associated with a prolonged sedentary bout. Methods: Ten young (24 ± 1 y) healthy males completed two 3-hour sessions of prolonged sitting with (SIT-EX) and without (SIT) a high-intensit...

PURPOSE: Inducible nitric oxide synthase (iNOS) is an enzyme expressed in leukocytes that supports innate immune function. While iNOS expression is low-to-undetectable in leukocytes under normal resting conditions, LPS-stimulated overexpression of iNOS increases indices of pro-inflammation, oxidative stress, and apoptosis. Aerobic exercise is a kno...

J. Weggen, A. Hogwood, B. Imthurn, A. McIntyre, A. Darling, K. Decker and R. Garten. Virginia Commonwealth University, Richmond, VA The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. Peripheral vascular dys...

Exercise intolerance is the cardinal symptom of heart failure (HF) and is of crucial relevance, because it is associated with a poor quality of life and increased mortality. While impaired cardiac reserve is considered to be central in HF, reduced exercise and functional capacity are the result of key patient characteristics and multisystem dysfunc...

New finding: What is the central question of this study? This study sought to determine whether prior upper limb aerobic training can attenuate the vascular dysfunction resulting from negative alteration of blood flow patterns. What is the main finding and its importance? We demonstrated that the microvasculature of young men with prior upper limb...

Vascular function and blood flow responses to upper limb exercise are differentially altered in response to different exercise training modalities. Rowing is a unique exercise modality that incorporates the upper limbs and can significantly augment upper limb endurance, strength, and power capacity. Purpose: This study sought to determine whether...

OBJECTIVES/SPECIFIC AIMS: Cardiac radiation exposure following anti-cancer (CA) thoracic radiotherapy (RT) treatment increases risk of heart failure in a dose-dependent manner with a predominantly restrictive cardiomyopathy phenotype and is characterized by a diffuse fibrosis within the myocardium. The peak oxygen pulse (O2Pulse) determined at card...

The role of body composition in patients with heart failure (HF)has been receiving much attention in the last few years. Particularly, reduced lean mass (LM), the best surrogate for skeletal muscle mass, is independently associated with abnormal cardiorespiratory fitness (CRF)and muscle strength, ultimately leading to reduced quality of life and wo...

Background Aging is associated with augmented sympathetic nervous system activity, which promotes vasoconstriction in the peripheral circulation through the alpha‐adrenergic pathway. However, whether this age‐related sympathoexcitation restrains exercising skeletal muscle blood flow and vascular conductance remains poorly understood. Methods In ni...

This study examined if the degree of aerobic training protects against the lower limb vascular dysfunction associated with a prolonged sitting bout. Ten young, aerobically trained (AT) and 10 young, untrained (UT) individuals completed a prolonged (3 h) sitting bout. Leg vascular function was measured prior to and at 1.5 and 3 h into the prolonged...

Aim: To examine the impact of aging on neuromuscular fatigue following cycling (CYC; large active muscle mass) and single-leg knee-extension (KE; small active muscle mass) exercise. Methods: Eight young (25{plus minus}4years) and older (72{plus minus}6years) participants performed CYC and KE to task-failure at a given relative intensity (80% of...

Austin C. Hogwood, Jennifer Weggen, Carson Fralin, David Lee, Matthew Scott, and Ryan S. Garten. Virginia Commonwealth University, Richmond, VA. Reactive oxygen and nitrogen species (RONS) have been revealed to incur both positive and negative changes to physiological function and adaptation. Specific to the peripheral vasculature, RONS can act to...

Dynamic exercise evokes an increase in sympathetic nervous system (SNS) activity, a response that contributes to the “fine‐tuning” of blood flow to meet the metabolic demands of active skeletal muscle. Expression of this exercise‐induced increase in SNS activity is blunted within the vasculature of exercising muscle, an event known as “functional s...

Background The sympathetic nervous system plays an important role in regulating skeletal muscle blood flow at rest and during exercise. Previous studies have identified sex differences in resting muscle sympathetic nerve activity1 and forearm alpha‐adrenergic receptor sensitivity.2 However, whether sympathetic restraint of limb blood flow differs b...

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this...

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction: however little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ±4 yr) and 15 age-...

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 ag...

The vasodilatory response to passive leg movement (PLM) appears to provide a novel, non-invasive assessment of vascular function. However, PLM has yet to be compared to the established non-invasive assessment of vascular health, flow mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM, upright seated and su...

While theoretically sound, the accuracy and precision of (31)P-magnetic resonance spectroscopy ((31)P-MRS) approaches to quantitatively estimate mitochondrial capacity are not well documented. Therefore, employing four differing models of respiratory control (linear, kinetic and multi-point adenosine diphosphate (ADP), and phosphorylation potential...

BACKGROUND The impact of aging on exercise induced fatigue is inconclusive with many studies ascribing a greater fatigue resistance to older individuals. PURPOSE To examine the effect of aging on fatigue resistance during dynamic and isometric small muscle mass exercise, both performed at a given absolute work rate and relative exercise intensity....

Background Passive leg movement (PLM) has been developed as a non‐invasive model for assessing nitric oxide (NO)‐mediated vascular function, and has recently been utilized to demonstrate vascular dysfunction in heart failure with reduced ejection fraction (HFrEF) patients [1]. Tetrahydrobiopterin (BH 4 ) is an essential cofactor of endothelial nitr...

The vasodilatory response to passive leg movement (PLM), often performed in either the upright seated or supine posture, appears to provide a novel, non‐invasive assessment of vascular function. However, PLM has yet to be compared to flow mediated vasodilation (FMD), a test recognized to have prognostic value in terms of vascular health. Therefore,...

PURPOSE Aging is associated with an increase in oxidant production that negatively impacts vascular function. This vascular dysfunction is, in part, mediated by a decrease in endothelial nitric oxide synthase (eNOS) activity. Tetrahydrobiopterin (BH4), an important co‐factor involved in eNOS coupling, is highly susceptible to oxidation and therefor...

Heightened muscle sympathetic nerve activity (MSNA) is associated with impaired vasodilatory capacity and vascular dysfunction linked to aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during continuous passive limb movement (PLM), a novel method to assess vascular function, has not been determined....

Passive leg movement (PLM) is emerging as a potentially better assessment of nitric oxide (NO)‐mediated vascular function than brachial artery flow‐mediated dilation, as it elicits a robust NO‐mediated increase in both leg vascular conductance (LVC) and leg blood flow (LBF). Typically, PLM is conducted with continuous movements spanning one to two...

Introduction: Due to reduced nitric oxide (NO) bioavailability with age, passive leg movement (PLM)-induced vasodilation is attenuated in older sedentary subjects and, unlike the young, cannot be augmented by posture-induced elevations in femoral perfusion pressure. However, whether vasodilator function assessed with PLM, and therefore NO bioavail...

Background: Exercise intolerance is a hallmark symptom of heart failure patients with preserved ejection fraction (HFpEF), which may be related to an impaired ability to appropriately increase blood flow to the exercising muscle. Methods: We evaluated leg blood flow (LBF, ultrasound Doppler), heart rate (HR), stroke volume (SV), cardiac output (...

Post cuff occlusion flow mediated dilation (FMD) is a proposed indicator of Nitric Oxide (NO)-bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates po...

Objective: While vascular dysfunction is well defined in patients with heart failure (HF) with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of patients with HF with preserved ejection fraction (HFpEF) are not well characterised. Thus, we sought to test the hypothesis that patients with HFpEF would de...

Key points The concept of symmorphosis predicts that the capacity of each step of the oxygen cascade is attuned to the task demanded of it during aerobic exercise at maximal rates of oxygen consumption ( ) such that no single process is limiting or in excess at . The present study challenges the applicability of this concept to humans by revealing...

This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with COPD. Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex...

Using flow-mediated vasodilation (FMD) and reactive hyperemia (RH), this study aimed to provide greater insight into left ventricular assist device (LVAD)-induced changes in peripheral vascular function. Peripheral endothelial function is recognized to be impaired in patients with heart failure with reduced ejection fraction (HFrEF), but the periph...

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow, and the transport and utilization of oxygen (O2) in patients with chronic obstructive pulmonary disease (COPD) is not well understood. This study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic e...

This study sought to examine the effects of partial vascular occlusion (PVO) on oxidative stress markers in response to resistance exercise and at rest in young resistance-trained males. 12 resistance-trained males performed 6 conditions in random counterbalanced order: rest (R), low-intensity (LIRE: 30% 1RM) and moderate-intensity (MIRE: 70% 1RM)...

The present study aimed to determine the day to day variability and reliability of several blood oxidative stress markers at rest in a healthy young cohort over a four-week period. Twelve apparently healthy resistance trained males (24.6 ± 3.0 yrs) were tested over 7 visits within 4 weeks with at least 72 hrs between visits at the same time of day....

Key points We aimed to elucidate the role of group III/IV locomotor muscle afferents in the development of central fatigue and the responsiveness of the corticospinal tract in relation to an unexercised arm muscle. Intrathecal fentanyl, a μ‐opioid receptor agonist, was employed to attenuate afferent feedback from the leg muscles during intense cycl...

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac, skeletal, and smooth muscle was harvested from a total of...