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Author: Matthew D Muller (53)


Aug
2017

The purpose of this study was to investigate blood pressure (BP) and leg skeletal muscle oxygen saturation (SmO2) during treadmill walking in patients with peripheral artery disease (PAD) and healthy subjects. Eight PAD patients (66 ± 3 years, 1 female) and eight healthy subjects (65 ± 2 years, 1 female) walked on a treadmill at 2 miles/hour. The incline increased by 2% every 2 minutes from 0% to 15% or until maximal discomfort.

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Aug
2017

During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs.

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Jul
2017

Peripheral artery disease (PAD) is an atherosclerotic vascular disease that affects 200 million people worldwide. Although PAD primarily affects large arteries, it is also associated with microvascular dysfunction, an exaggerated blood pressure (BP) response to exercise, and high cardiovascular mortality. We hypothesized that fatiguing plantar flexion exercise that evokes claudication elicits a greater reduction in skeletal muscle oxygenation (SmO2) and a higher rise in BP in PAD compared with age-matched healthy subjects, but low-intensity steady-state plantar flexion elicits similar responses between groups.

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Mar
2017

Despite its widespread clinical use, the β1-adrenergic receptor antagonist esmolol hydrochloride is not commonly used in human physiology research, and the effective dose of esmolol (compared with the nonselective β-blocker propranolol) is unclear. In four separate studies we used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate (HR)-lowering effect of esmolol compared with propranolol and saline in healthy humans. In cohort 1, both esmolol (ΔHR 57 ± 6 beats/min) and propranolol (ΔHR 56 ± 7 beats/min) attenuated exercise tachycardia compared with saline (ΔHR 88 ± 17 beats/min).

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Oct
2016

Blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) has the potential to quantify skeletal muscle oxygenation with high temporal and high spatial resolution. The purpose of this study was to characterize skeletal muscle BOLD responses during steady-state plantar flexion exercise (i.e.

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Jul
2017

To evaluate the dynamic characteristics of T2* -weighted signal change in exercising skeletal muscle of healthy subjects and peripheral artery disease (PAD) patients under a low-intensity exercise paradigm.
Nine PAD patients and nine age- and sex-matched healthy volunteers underwent a low-intensity exercise paradigm while magnetic resonance imaging (MRI) (3.0T) was obtained.

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Jan
2017

Peripheral arterial disease (PAD) is an atherosclerotic vascular disease that affects over 200 million people worldwide. The hallmark of PAD is ischemic leg pain and this condition is also associated with an augmented blood pressure response to exercise, impaired vascular function, and high risk of myocardial infarction and cardiovascular mortality. In this study, we tested the hypothesis that coronary exercise hyperemia is impaired in PAD.

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May
2016

Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α-adrenergic receptors and β-adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone.

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Aug
2015

Epidemiologic data suggest there are seasonal variations in the incidence of severe cardiac events with peak levels being evident in the winter. Whether autonomic indices including muscle sympathetic nerve activity (MSNA) vary with season remains unclear. In this report, we tested the hypothesis that resting MSNA varies with the seasons of the year with peak levels evident in the winter.

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Nov
2015

Exposure to hypoxia is associated with cognitive impairment, mediated by cerebral deoxygenation. This can be problematic for individuals who perform mental tasks at high altitude. Eight healthy men completed two experimental trials consisting of 5h of exposure to normobaric hypoxia (12.

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Sep
2015

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation.

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Aug
2015

Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex. Humans with peripheral arterial disease (PAD) have an augmented exercise pressor reflex, but the metabolite(s) responsible for this augmented response is not known. We tested the hypothesis that intravenous injection of ketorolac, which blocks the activity of cyclooxygenase, would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) evoked by plantar flexion exercise.

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Apr
2015

We recently demonstrated that postmenopausal women have an augmented blood pressure response to voluntary apnea compared to premenopausal women. Both obstructive sleep apnea (OSA) and healthy aging are associated with increased oxidative stress, which may impair cardiovascular function. Restoring physiological responses could have clinical relevance since transient surges in blood pressure are thought to be an important stimulus for end-organ damage in aging and disease.

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Oct
2014

Voluntary apnea activates the central and peripheral chemoreceptors, leading to a rise in sympathetic nerve activity and limb vasoconstriction (i.e., brachial blood flow velocity and forearm cutaneous vascular conductance decrease to a similar extent).

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Nov
2014

Patients with coronary artery disease have attenuated coronary vasodilator responses to physiological stress, which is partially attributed to a β-adrenergic receptor (β-AR)-mediated mechanisms. Whether β-ARs contribute to impaired coronary vasodilation seen with healthy aging is unknown. The purpose of this study was to investigate the role of β-ARs in coronary exercise hyperemia in healthy humans.

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Jul
2014

In response to hypoxia, a net vasodilation occurs in the limb vasculature in young healthy humans and this is referred to as "hypoxia-induced vasodilation". We performed two separate experiments to determine (1) if hypoxia-induced forearm vasodilation is impaired in older men (n = 8) compared to young men (n = 7) and (2) if acute systemic infusion of ascorbic acid would enhance hypoxia-induced vasodilation in older men (n = 8). Heart rate, mean arterial pressure, oxygen saturation, minute ventilation, forearm vascular conductance (FVC, Doppler ultrasound), and cutaneous vascular conductance (CVC, laser Doppler flowmetry) were recorded continuously while subjects breathed 10% oxygen for 5 min.

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Jul
2014

Cardiac ischemia and angina pectoris are commonly experienced during exertion in a cold environment. In the current study we tested the hypotheses that oropharyngeal afferent blockade (i.e.

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Dec
2013

Forearm vascular conductance (FVC) increases in response to mental stress (verbal mental arithmetic) in young people. However, the effect of healthy aging and mental stress on FVC is unknown. In this study, we tested the hypothesis that FVC and cutaneous vascular conductance (CVC) would be attenuated in older adults compared to young adults.

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Mar
2014

Forehead cooling activates the sympathetic nervous system and can trigger angina pectoris in susceptible individuals. However, the effect of forehead cooling on coronary blood flow velocity (CBV) is not well understood. In this human experiment, we tested the hypotheses that forehead cooling reduces CBV (i.

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Nov
2013

Peripheral arterial disease (PAD) patients have augmented blood pressure increases during exercise, heightening their cardiovascular risk. However, it is unknown whether patients have exaggerated renal vasoconstriction during exercise and if oxidative stress contributes to this response. Eleven PAD patients and 10 controls (CON) performed 4-min mild, rhythmic, plantar flexion exercise of increasing intensity (0.

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Feb
2014

Clinical evidence indicates that obstructive sleep apnea is more common and more severe in men compared with women. Sex differences in the vasoconstrictor response to hypoxemia-induced sympathetic activation might contribute to this clinical observation. In the current laboratory study, we determined sex differences in the acute physiological responses to maximal voluntary end-expiratory apnea (MVEEA) during wakefulness in healthy young men and women (26 ± 1 yr) as well as healthy older men and women (64 ± 2 yr).

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Jan
2014

Animal studies indicate alpha-adrenergic coronary vasoconstriction helps maintain left ventricular function during physiological stress. Whether this process occurs in humans is unknown. In the current study, we used transthoracic Doppler echocardiography to test the effect of lower body negative pressure (LBNP) on coronary blood flow velocity (CBV, left anterior descending coronary artery) and myocardial function in eight young healthy subjects before and after systemic infusion of phentolamine, a nonselective alpha blocker.

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Aug
2013

Reactive oxygen species (ROS), produced acutely during skeletal muscle contraction, are known to stimulate group IV muscle afferents and accentuate the exercise pressor reflex (EPR) in rodents. The effect of ROS on the EPR in humans is unknown. We conducted a series of studies using ischemic fatiguing rhythmic handgrip to acutely increase ROS within skeletal muscle, ascorbic acid infusion to scavenge free radicals, and hyperoxia inhalation to further increase ROS production.

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Sep
2013

The physiological effects of immersion hypothermia and afterdrop are well-characterized, but the psychological effects are less clear. The purpose of this study was to quantify changes in cognitive function during and after lower body water immersion.
On separate mornings, nine young healthy men participated in both neutral (35 +/- 1 degree C) and cold (13 +/- 1 degree C) water immersion.

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Nov
2013

Melatonin attenuates the skin sympathetic nerve response to mental stress.

Am J Physiol Heart Circ Physiol 2013 Nov 30;305(9):H1382-6. Epub 2013 Aug 30.
Matthew D Muller, Charity L Sauder, Chester A Ray
Melatonin attenuates muscle sympathetic nerve responses to sympathoexcitatory stimuli, but it is unknown whether melatonin similarly attenuates reflex changes in skin sympathetic nerve activity (SSNA). In this double-blind, placebo-controlled, crossover study, we tested the hypothesis that melatonin (3 mg) would attenuate the SSNA response to mental stress (mental arithmetic). Twelve healthy subjects underwent experimental testing on two separate days.

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Nov
2013

Peripheral arterial disease (PAD) is an atherosclerotic condition that can provoke symptoms of leg pain ("intermittent claudication") during exercise. Because PAD is often observed with comorbid conditions such hypertension, dyslipidemia, diabetes, cigarette smoking, and/or physical inactivity, the pathophysiology of PAD is certainly complex and involves multiple organ systems. Patients with PAD are at high risk for myocardial infarction, stroke, and all-cause mortality.

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Oct
2013

Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex (CBR)-heart rate (HR) control during local metabolite accumulation in humans. However, the contribution of thromboxane A2 (TXA2) toward this response is unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in humans was examined.

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Mar
2013

Mental stress (MS) is a known trigger of myocardial infarction and sudden death. By activating the sympathetic nervous system, MS may have deleterious effect on the cardiovascular system but this process is not completely understood. The primary aim of this study was to quantify the effect of MS on skin sympathetic nerve activity (SSNA).

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Jul
2013

Sympathetically mediated renal vasoconstriction may contribute to the pathogenesis of hypertension in older adults, but empirical data in support of this concept are lacking. In 10 young (26 ± 1 yr) and 11 older (67 ± 2 yr) subjects, we quantified acute hemodynamic responses to three sympathoexcitatory stimuli: local cooling of the forehead, cold pressor test (CPT), and voluntary apnea. We hypothesized that all stimuli would increase mean arterial blood pressure (MAP) and renal vascular resistance index (RVRI) and that aging would augment these effects.

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Jul
2013

Tactile stimulation of the oropharynx (TSO) elicits the gag reflex and increases heart rate (HR) and mean arterial pressure (MAP) in anesthetized patients. However, the interaction between upper-airway defense reflexes and the sympathetic nervous system has not been investigated in conscious humans. In Experiment 1, beat-by-beat measurements of HR, MAP, muscle sympathetic nerve activity (MSNA), and renal vascular resistance (RVR) were measured during TSO and tactile stimulation of the hard palate (Sham) in the supine posture.

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Apr
2014

When exposed to a cold environment, a barehanded person experiences pain, cold sensation, and reduced manual dexterity. Both acute (e.g.

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Jan
2013

We sought to determine how the aging left ventricle (LV) responds to sympathetic nervous system (SNS) activation. Three separate echocardiographic experiments were conducted in 11 healthy young (26 ± 1 yr) and 11 healthy older (64 ± 1 yr) adults. Tissue Doppler imaging was used to measure systolic myocardial velocity (S(m)), early diastolic myocardial velocity (E(m)), and late diastolic myocardial velocity (A(m)) during isometric fatiguing handgrip (IFHG), a 2-min cold pressor test (CPT), and 5 min of normobaric hypoxia.

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Oct
2012

Lower body water immersion (LBWI) is experienced in the marine industry but the physiological responses to LBWI are unclear. The purpose of the current experiment was to test the effects of water temperature and immersion duration on rectal temperature, heart rate, stroke volume, blood pressure, metabolic rate, and thermal sensation in healthy subjects.
Nine young men underwent two 60-min trials of seated LBWI to the iliac crest in a counterbalanced fashion.

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Dec
2012

Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in patients with peripheral arterial disease (PAD). However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants. Three physiological studies were conducted in patients with PAD and controls.

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Feb
2013

Obesity is a disease of oxidative stress (OS). Acute hyperoxia (breathing 100 % O(2)) can evoke coronary vasoconstriction by the oxidative quenching of nitric oxide (NO). To examine if weight loss would alter the hyperoxia-related coronary constriction seen in obese adolescents, we measured the coronary blood flow velocity (CBV) response to hyperoxia using transthoracic Doppler echocardiography before and after a 4-week diet and exercise regimen in 6 obese male adolescents (age 13-17 years, BMI 36.

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Dec
2012

Sleep deprivation and cold air exposure are both experienced in occupational and military settings but the combined effects of these 2 stressors is unknown. The purpose of this study was to determine the effects of 53 hours of total sleep deprivation on thermoregulation during the rewarming phase (25°C air) after acute cold air exposure (10°C air).
Eight young men underwent 2 trials in which they either received 7 hours of sleep at night or were totally sleep deprived.

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Jun
2012

Several industries experience periods of cold exposure and rewarming throughout the workday but mental performance under these conditions is unknown. A better understanding of cognition during the rewarming phase after cold exposure may help reduce accidents and improve performance. Ten young men (wearing ~0.

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Apr
2012

The purpose of this echocardiography study was to measure peak coronary blood flow velocity (CBV(peak)) and left ventricular function (via tissue Doppler imaging) during separate and combined bouts of cold air inhalation (-14 ± 3°C) and isometric handgrip (30% maximum voluntary contraction). Thirteen young adults and thirteen older adults volunteered to participate in this study and underwent echocardiographic examination in the left lateral position. Cold air inhalation was 5 min in duration, and isometric handgrip (grip protocol) was 2 min in duration; a combined stimulus (cold + grip protocol) and a cold pressor test (hand in 1°C water) were also performed.

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Mar
2012

Low-dose caffeine administered in chewing gum does not enhance cycling to exhaustion. The purpose of the current investigation was to examine the effect of low-dose caffeine (CAF) administered in chewing gum at 3 different time points during submaximal cycling exercise to exhaustion. Eight college-aged (26 ± 4 years), physically active (45.

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Sep
2011

Previous studies have shown that single bouts of high-rate active cycling (> 80 rpm) improve upper extremity motor function in individuals with Parkinson's disease (PD). It is unknown if passive leg cycling produces a similar effect on upper extremity function. This article examines whether passive leg cycling can promote immediate changes in upper tremor and bradykinesia in PD and if pedaling rates have variable effects.

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Nov
2011

In the cold, Purdue Pegboard (PP) performance declines. The purpose of this study was to determine if this cold-induced impairment is consistent across days (i.e.

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Dec
2011

The effects of cold air inhalation and isometric exercise on coronary blood flow are currently unknown, despite the fact that both cold air and acute exertion trigger angina in clinical populations. In this study, we used transthoracic Doppler echocardiography to measure coronary blood flow velocity (CBV; left anterior descending coronary artery) and myocardial function during cold air inhalation and handgrip exercise. Ten young healthy subjects underwent the following protocols: 5 min of inhaling cold air (cold air protocol), 5 min of inhaling thermoneutral air (sham protocol), 2 min of isometric handgrip at 30% of maximal voluntary contraction (grip protocol), and 5 min of isometric handgrip at 30% maximal voluntary contraction while breathing cold air (cold + grip protocol).

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Dec
2011

To explore the effect of aspirin on the thermoregulatory responses of men during exposure to 12°C air (acute cold exposure) for a period of 120 minutes and recovery in 25°C air (rewarming) for 120 minutes.
Seven male subjects (26.1 ± 2.

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Feb
2012

We sought to determine if cold acclimatized men display higher economy (i.e. lower oxygen consumption at a given workload) during graded cycle ergometry in the cold (5°C).

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Feb
2012

Supplementary oxygen is commonly administered in current medical practice. Recently it has been suggested that hyperoxia causes acute oxidative stress and produces prompt and substantial changes in coronary resistance in patients with ischemic heart disease. In this report, we examined whether the effects of hyperoxia on coronary blood velocity (CBV) would be associated with a reduction in myocardial function.

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Apr
2011

Individuals with Parkinson's disease (PD) often experience cognitive declines. Although pharmacologic therapies are helpful in treating motor deficits in PD, they do not appear to be effective for cognitive complications. Acute bouts of moderate aerobic exercise have been shown to improve cognitive function in healthy adults.

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Jun
2011

Salt intake may cause conflict for the cardiovascular system as it attempts to simultaneously maintain blood pressure (BP) and temperature homeostasis. Our objective was to determine the effect of a salt and water load vs. a water load upon rectal temperature (Tre) in healthy volunteers.

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Mar
2011

"Rewarming" an important issue from the cold: simulated avalanche survival and the physiology of afterdrop.

Wilderness Environ Med 2011 Mar 23;22(1):98-9; author reply 99-100. Epub 2010 Oct 23.
Matthew D Muller

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Jul
2011

Both mood and cognitive function are altered in cold environments. Body warming through exercise may improve Stroop interference score and lessen total negative mood. The purpose of this study was to determine the effect of equal caloric bouts of interval (INT) and continuous (CONT) exercise on mood and selective attention in the cold.

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Jun
2011

Military and factory work often involves exposure to cold temperatures. With prolonged exposure, individuals report feeling cold and develop pain in their hands, both of which might be alleviated by endogenous heat production via exercise. The purpose of this study was to evaluate how interval (INT) and continuous (CONT) cycle ergometry alter thermal sensation, hand pain, mean finger temperature, and skin surface temperature gradient (forearm-finger) following immobility in moderate cold.

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