Zachary Barrett-O'Keefe

• PhD RDCS
• Mayo Clinic - Rochester

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...

While there is emerging evidence of peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction (HFpEF) that may be related to systemic inflammation and redox imbalance, disease-related changes in locomotor muscle microvascular responsiveness have not been determined. This study combined passive leg movement...

The clinical distinction between athlete's heart and structural heart disease in the echocardiography laboratory is often challenging. We present a case where athletic heart syndrome was promptly differentiated from pathology with a simple maneuver during echocardiography.

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in alpha-adrenergic receptor vasoconstriction. Thus, in eight HFrEF patients (63 ± 4 yrs) and eight well-matched controls (63 ± 2 yrs) we examined changes in leg blood flow...

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...

New findings: What is the central question of this research? Do patients with heart failure with reduced ejection fraction (HFrEF) exhibit a greater dependence on cardiac or peripheral vascular haemodynamics across multiple levels of muscle metaboreflex activation provoked by postexercise circulatory occlusion? What is the main finding and its imp...

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...

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis, however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administ...

Background: Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution...

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...

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...

Systemic sclerosis (SSc) vasculopathy can result in a digital ulcer (DU) and/or pulmonary arterial hypertension (PAH). We hypothesized that bedside brachial artery flow-mediated dilation (FMD) testing with duplex ultrasound could be used in SSc patients to identify features of patients at risk for DU or PAH. Thirty-eight SSc patients were compared...

To better understand the mechanisms responsible for exercise intolerance in heart failure with reduced ejection fraction (HFrEF), the present study sought to evaluate the hemodynamic responses to small muscle mass exercise in this cohort. In 25 HFrEF patients (64 ± 2 yrs) and 17 healthy, age-matched control subjects (64 ± 2 yrs), mean arterial pres...

The endothelin-1 vasoconstrictor pathway contributes to age-related elevations in resting peripheral vascular tone primarily through activation of the endothelin subtype A (ETA) receptor. However, the regulatory influence of ETA-mediated vasoconstriction during exercise in the elderly is unknown. Thus, in 17 healthy volunteers (n = 8 young, 24±2 ye...

Exercise intolerance is a hallmark characteristic of heart failure (HF), which may be related to impaired exercise‐induced vasodilation in the exercising muscle vasculature. While reductions in exercising limb blood flow have been observed in patients with systolic HF no studies, to date, have evaluated vasodilation in HF patients with preserved ej...

While peripheral vascular dysfunction is well‐described in heart failure patients with reduced ejection fraction, disease‐related changes in vascular function in heart failure patients with preserved ejection fraction (HFpEF) remains unclear. Thus, in six HFpEF patients (73 ± 4 yrs) and six healthy controls matched for age (74 ± 4 yrs), sex, and br...

Unlabelled: The reduction in nitric oxide (NO)-mediated vascular function with age has largely been determined by flow-mediated dilation (FMD). However, in light of recent uncertainty surrounding the NO dependency of FMD and the recognition that brachial artery (BA) vasodilation during handgrip exercise is predominantly NO-mediated in the young, w...

To better define the role of sympathetic vasoconstriction in the regulation of exercising skeletal muscle blood flow, five healthy men (24 ± 1 yrs) performed knee‐extensor exercise at 0, 5, 10, and 15 watts during intra‐arterial infusion of phenylephrine (PE, alpha‐1 agonist), phentolamine (PHEN, non‐selective alpha adrenergic antagonist), and sali...

to the editor: We thank Pancheva and colleagues ([4][1]) for penning a Letter to the Editor regarding our paper in which they bring attention to the potential role of metabolic heat and carbon dioxide (CO2) production in the alteration of skeletal muscle blood flow induced by maximal strength

The cardiovascular response to exercise is governed by a combination of vasodilating and vasoconstricting influences that optimize exercising muscle perfusion while protecting mean arterial pressure (MAP). The degree to which endogenous endothelin-1 (ET-1), the body's most potent vasoconstrictor, participates in this response is unknown. Thus, in e...

Aging is characterized by increased sympathoexcitation, expressed through both the alpha-adrenergic and renin-angiotensin-aldosterone (RAAS) pathways. While the independent contribution of these two pathways to elevated vasoconstriction with age may be substantial, significant cross-talk exists that could produce potentiating effects. To examine th...

Maximal strength training (MST) reduces pulmonary oxygen uptake (VO(2)) at a given submaximal exercise work rate (i.e. efficiency). However, whether the increase in efficiency originates in the trained skeletal muscle, and therefore the impact of this adaptation on muscle blood flow and arterial-venous oxygen difference (a-vO(2diff)), is unknown. T...

New findings What is the central question of this study? The role of histamine‐mediated vasodilatation has been studied in the context of whole‐body cycling but not small muscle‐mass exercise. What is the main finding and its importance? These data indicate that histamine receptors are activated following dynamic, but not resistance, exercise. Furt...

Using flow-mediated vasodilation (FMD), reactive hyperemia, and an acute oral antioxidant cocktail (AOC; vitamins C and E and α-lipoic acid), this study aimed to provide greater insight into altered vascular function and the role of oxidative stress in chronic heart failure patients with reduced ejection fraction (HFrEF) and at several time points...

Recently, our group published a study in Hypertension that used flow-mediated vasodilation (FMD) and reactive hyperemia to assess the impact of an enteral antioxidant (AO) mixture, of known efficacy, on the endothelial dysfunction associated with aging.1 In a Letter to the Editor, Tsikas et al2 expressed some concern regarding the divergent FMD and...

Exercise intolerance is a hallmark symptom of heart failure (HF), which may be due, in part, to an exaggerated exercise pressor reflex. Thus, the objective of this study was to better define the magnitude and mechanisms of the exercise pressor response in HF. Six HF patients (NYHA Class II‐III) and six young, healthy controls performed dynamic hand...

Aging is associated with a pro-oxidant state and a decline in endothelial function. Whether acute, enteral antioxidant treatment can reverse this decrement in vascular function is not well known. Flow-mediated vasodilation and reactive hyperemia were evaluated after consumption of either placebo or an oral antioxidant cocktail (vitamin C, 1000 mg;...

We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre...

Skeletal muscle vasodilatation persists following a single bout of exercise and can potentially influence glucose uptake by recovering muscle. To investigate whether blood flow is a rate-limiting component in postexercise muscle glucose uptake, we tested the hypothesis that oral ingestion of H(1)- and H(2)-receptor antagonists, known to attenuate t...

This study used alterations in body position to identify differences in hemodynamic responses to passive exercise. Central and peripheral hemodynamics were noninvasively measured during 2 min of passive knee extension in 14 subjects, whereas perfusion pressure (PP) was directly measured in a subset of 6 subjects. Movement-induced increases in leg b...

The purpose of this investigation was to partially remove feedback from type III/IV skeletal muscle afferents and determine how this feedback influences the central and peripheral hemodynamic responses to passive leg movement. Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure, leg vascular conductance (LVC), and leg b...

Initial observations in moderately fit endurance‐trained men have shown decreases in cardiac output with no change in systemic vascular conductance during postexercise hypotension, in contrast to other populations. As inadequate hydration could have been a cause for the differences, we decided to study a larger group of highly fit endurance‐trained...