Papers by Kevin Shoemaker
Sympathetic nerve activity plays an essential role in the normal regulation of blood pressure in ... more Sympathetic nerve activity plays an essential role in the normal regulation of blood pressure in humans and in the etiology and progression of many chronic diseases. Sympathetic nerve recordings associated with blood pressure regulation can be recorded directly using microneurography. A general characteristic of this signal is spontaneous burst activity of spikes (action potentials) separated by silent periods against a background of considerable gaussian noise. During measurement with electrodes, the raw muscle sympathetic nerve activity (MSNA) signal is amplified, band-pass filtered, rectified and integrated. This integration process removes important information regarding action potential content and their discharge properties. The first objective of this thesis was to propose a new method for detecting action potentials from the raw MSNA signal to enable investigation of post-ganglionic neural discharge properties. The new method is based on the design of a mother wavelet that is matched to an actual mean action potential template extracted from a raw MSNA signal and applying it to the raw MSNA signal using a continues wavelet transform (CWT) for spike detection. The performance of the proposed method versus two previous wavelet-based approaches was evaluated using 1) MSNA recorded from seven healthy participants and, 2)simulated MSNA. The results show that the new matched wavelet performs better than the previous wavelet-based methods that use a non-matched wavelet in detecting action potentials in the MSNA signal. The second objective of this thesis was to employ the proposed action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human MSNA signal. While in other neural systems (e.g. the skeletal motor system) there is a well understood pattern of neural recruitment during activation, our understanding of how sympathetic neurons are coordinated during baseline and baroreceptor unloading are very limited. We demonstrate that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger. This information has important implications for how blood pressure is controlled, and the malleability of sympathetic activaiii tion in health and disease.
Cardiovascular Research, Jul 1, 1997
Objective: Whether the dimensions of conduit arteries contribute to the time course of change in ... more Objective: Whether the dimensions of conduit arteries contribute to the time course of change in blood flow during voluntary rhythmic exercise, and the mechanisms governing such a response in humans, are not known. Methods: The time course of change in the vascular and blood flow dynamics in the brachial artery during the transition between rest and 5 min of rhythmic handgrip exercise was Ž. Ž. assessed in humans using continuous measures of brachial artery mean blood velocity MBV; pulsed Doppler , diameter echo Doppler Ž. Ž. Ž. and mean arterial pressure Finapres. The exercise cadence was 1sr1s Fast and 1sr2s Slow workrrest schedules while supine with the arm positioned above or below the heart. Results: Brachial artery diameter of the active arm was reduced 5% at ; 10 s following the Ž. onset of exercise performed above the heart P-0.05 , irrespective of work rate, and returned to rest levels by 30 s with no concurrent changes in arterial pressure. By 2 min of the Fast contraction rate exercise, brachial artery diameter of the active arm was greater than rest Ž. P-0.05 irrespective of arm position. Brachial artery dimensions in the contralateral inactive arm were not altered during exercise Ž. P) 0.05. Compared with rest, MBV and forearm blood flow at 5 s of exercise were increased in the active arm but were reduced Ž. transiently in the inactive limb P-0.05. Conclusions: Conduit artery responses to exercise were dependent upon the work rate and arm position. The delayed dilation in the heavier exercise, independent of arm position, suggests that stimuli related to the metabolic activity of the distal active skeletal muscle may influence the dimensions of the conduit artery. q 1997 Elsevier Science B.V.
Physiological Reports
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Nine healthy volunteers performed a series of single handgrip isometric contractions to test the ... more Nine healthy volunteers performed a series of single handgrip isometric contractions to test the hypothesis that the blood flow response to a contraction is determined solely by the tension-time index (isometric analog of work). Contractions were performed in duplicate at 15, 30, and 60% of maximal voluntary contraction (MVC) at durations of 0.5, 1, and 2 s. Forearm blood flow (FBF) was measured beat by beat by using Doppler ultrasound. Peak FBF responded in a graded fashion to graded increases in peak tension with contraction time held constant (35, 56, and 90 ml/min for 15, 30, and 60% MVC for 1 s, respectively). When tension was kept constant, peak FBF responded in a graded fashion to graded increases in duration (77, 90, and 97 ml/min for 60% MVC for 0.5, 1, and 2 s). With a constant tension-time index, peak FBF responded in a graded fashion to graded increases in peak tension (48, 56, and 77 ml/min for 15% MVC/2 s, 30% MVC/1 s, and 60% MVC/0.5 s). Similar trends were also observed for total postcontraction hyperemia. Blood flow increased regardless of whether the change in tension-time index was accomplished by an increase in tension or duration of contraction. However, with a constant tension-time index, the change in blood flow was related to the peak tension developed. Our results suggest that the blood flow response to a single muscle contraction is not determined solely by the work performed (tension-time index) but also by the number of muscle fibers recruited.
Journal of the American Heart Association, 2018
Background Although the increased prevalence and severity of clinical depression and elevated car... more Background Although the increased prevalence and severity of clinical depression and elevated cardiovascular disease risk represent 2 vexing public health issues, the growing awareness of their combined presentation compounds the challenge. The obese Zucker rat, a model of the metabolic syndrome, spontaneously develops significant depressive symptoms in parallel with the progression of the metabolic syndrome and, thus, represents a compelling model for study. The primary objective was to assess the impact on both cardiovascular outcomes, specifically vascular structure and function, and depressive symptoms in obese Zucker rats after aggressive treatment for cardiovascular disease risk factors with long‐term exercise or targeted pharmacological interventions. Methods and Results We chronically treated obese Zucker rats with clinically relevant interventions against cardiovascular disease risk factors to determine impacts on vascular outcomes and depressive symptom severity. While mos...
Frontiers in Aging Neuroscience, 2016
Brain structure is a fundamental determinant of brain function, both of which decline with age in... more Brain structure is a fundamental determinant of brain function, both of which decline with age in the adult. Whereas short-term exercise improves brain size in older adults, the impact of endurance training on brain structure when initiated early and sustained throughout life, remains unknown. We tested the hypothesis that long-term competitive aerobic training enhances cortical and subcortical mass compared to middle to older-aged healthy adults who adhere to the minimum physical activity guidelines. Observations were made in 16 masters athletes (MA; 53 ± 6 years, VO = 2max 55 ± 10 ml/kg/min, training > 15 years), and 16 active, healthy, and cognitively intact subjects (HA; 58 ± 9 years, VO = 2max 38 ± 7 ml/kg/min). T1-weighted structural acquisition at 3T enabled quantification of cortical thickness and subcortical gray and white matter volumes. Cardiorespiratory fitness correlated strongly with whole-brain cortical thickness. Subcortical volumetric mass at the lateral ventricles, R hippocampus, R amygdala, and anterior cingulate cortex, correlated with age but not fitness. In a region-of-interest (ROI) group-based analysis, MA expressed greater cortical thickness in the medial prefrontal cortex, pre and postcentral gyri, and insula. There was no effect of group on the rate of age-related cortical or subcortical decline. The current data suggest that lifelong endurance training that produces high levels of cardiorespiratory fitness, builds cortical reserve early in life, and sustains this benefit over the 40-70 year age span. This reserve likely has important implications for neurological health later in life.
American journal of physiology. Heart and circulatory physiology, 2018
While it is known that chronic stress and clinical depression are powerful predictors of poor car... more While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and depressive symptoms, creating a combined condition of severely elevated cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs) and the unpredictable chronic mild stress (UCMS) model to determine the impact of preexisting metabolic disease on the relationship between chronic stress/depressive symptoms and vascular function. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive effects on vascular function in female lean Zucker rats (LZRs). In general, vasodilator reactivity was attenuated under control conditions in OZRs compared with LZRs. Although still impaired, conduit arterial and resistance arteriolar dilator reactivity under control conditions in female OZRs was superior to ...
BMC Geriatrics, 2016
Background: Dementia is associated with cognitive and functional deficits, and poses a significan... more Background: Dementia is associated with cognitive and functional deficits, and poses a significant personal, societal, and economic burden. Directing interventions towards older adults with self-reported cognitive complaints may provide the greatest impact on dementia incidence and prevalence. Risk factors for cognitive and functional deficits are multifactorial in nature; many are cardiovascular disease risk factors and are lifestyle-mediated. Evidence suggests that multiple-modality exercise programs can provide cognitive and functional benefits that extend beyond what can be achieved from cognitive, aerobic, or resistance training alone, and preliminary evidence suggests that novel mind-motor interventions (i.e., Square Stepping Exercise; SSE) can benefit cognition and functional fitness. Nevertheless, it remains unclear whether multiple-modality exercise combined with mind-motor interventions can benefit diverse cognitive and functional outcomes in older adults with cognitive complaints. Methods/Design: The Multiple-Modality, Mind-Motor (M4) study is a randomized controlled trial investigating the cognitive and functional impact of combined physical and cognitive training among community-dwelling adults with self-reported cognitive complaints who are 55 years of age or older. Participants are randomized to a Multiple-Modality and Mind-Motor (M4) intervention group or a Multiple-Modality (M2) comparison group. Participants exercise for 60 minutes/day, 3-days/week for 24 weeks and are assessed at baseline, 24 weeks and 52 weeks. The primary outcome is global cognitive function at 24 weeks, derived from the Cambridge Brain Sciences computerized cognitive battery. Secondary outcomes are: i) global cognitive function at 52 weeks; ii) domain-specific cognitive function at 24 and 52 weeks; iii) mobility (gait characteristics under single and dual-task conditions and balance); and 3) vascular health (blood pressure and carotid arterial measurements). We will analyze data based on an intent-to-treat approach, using mixed models for repeated measurements.
Frontiers in Aging Neuroscience, 2016
Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and ha... more Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre-and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control.
Journal of Critical Care, 2015
Early mobilization of critically ill patients is beneficial, suggesting that it should be incorpo... more Early mobilization of critically ill patients is beneficial, suggesting that it should be incorporated into daily clinical practice. Early passive, active, and combined progressive mobilizations can be safely initiated in intensive care units (ICUs). Adult patients receiving early mobilization have fewer ventilator-dependent days, shorter ICU and hospital stays, and better functional outcomes. Pediatric ICU data are limited, but recent studies also suggest that early mobilization is achievable without increasing patient risk. In this review, we provide a current and comprehensive appraisal of ICU mobilization techniques in both adult and pediatric critically ill patients. Contraindications and perceived barriers to early mobilization, including cost and health care provider views, are identified. Methods of overcoming barriers to early mobilization and enhancing sustainability of mobilization programs are discussed. Optimization of patient outcomes will require further studies on mobilization timing and intensity, particularly within specific ICU populations.
Journal of Applied Physiology, 2002
The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sle... more The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exh...
The Journal of Physiology, 2005
We recently reported that male, but not female, rats exhibit basal endogenous neuropeptide Y Y 1-... more We recently reported that male, but not female, rats exhibit basal endogenous neuropeptide Y Y 1-receptor modulation of hindlimb vasculature. The lack of baseline endogenous Y 1-receptor control in females was evident despite the expression of Y 1-receptors and neuropeptide Y in hindlimb skeletal muscle tissue. The following study addressed the hypothesis that neuropeptide Y bioavailability is blunted in female rats under baseline conditions. It was further hypothesized that enhanced prejunctional autoinhibitory neuropeptide Y Y 2-receptor expression and/or proteolytic processing of released neuropeptide Y may persist in female rats. Using western blot analysis, it was observed that females had greater overall neuropeptide Y Y 2-receptor expression in skeletal muscle compared to males (P < 0.05). To address the prevalence/impact of baseline endogenous Y 2-receptor activation on neuropeptide Y release in hindlimb vasculature, an arterial infusion of BIIE0246 (specific non-peptide Y 2-receptor antagonist; 170 µg kg −1) was carried out on female and male rats. Y 2-receptor blockade resulted in a decrease in hindlimb vascular conductance in females and males (P < 0.05). However, the BIIE0246-induced decrease in vascular conductance was Y 1-receptor dependent in females, but not males (P < 0.05). In addition, compared to baseline, BIIE0246 infusion resulted in increased plasma neuropeptide Y concentration in females (P < 0.05), while there was no observable change in males. In a final experiment, systemic inhibition of proteolytic enzymes dipeptidylpeptidase IV (via 500 nM diprotin A) and aminopeptidase P (via 180 nM 2-mercaptoethanol) elicited a Y 1-receptor-dependent decrease in hindlimb vascular conductance in females (P < 0.05). It was concluded that our previously reported lack of basal endogenous Y 1-receptor activation in female hindlimb vasculature was (at least partially) due to prejunctional Y 2-receptor autoinhibition and proteolytic processing of neuropeptide Y.
Stroke, 2001
Background and Purpose — Cerebrovascular autoregulation has been described with a phase lead of c... more Background and Purpose — Cerebrovascular autoregulation has been described with a phase lead of cerebral blood flow preceding changes in cerebral perfusion pressure (CPP), but there has been less focus on the effect of CPP on cerebral vascular resistance. We investigated these relations during spontaneous fluctuations (control) and repeated head-up tilt. Methods — Eight healthy adults were studied in supine rest and repeated tilt with 10-second supine, 10 seconds at 45° head-up tilt for a total of 12 cycles. Cerebral blood flow was estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP was estimated from corrected finger pressure (CPP F ), and cerebrovascular resistance index (CVRi) was calculated in the supine position from CPP F /MFV. Gain and phase relations were assessed by cross-spectral analysis. Results — In the supine position, MFV preceded CPP F , but changes in CVRi followed CPP F . Gain and phase relations for CPP F as input and MFV as output were...
Medicine & Science in Sports & Exercise, 2005
ABSTRACT Effects of exercise and/or diet on blood pressure (BP) have been well-documented; howeve... more ABSTRACT Effects of exercise and/or diet on blood pressure (BP) have been well-documented; however, their combined effects on overall cardiovascular functioning in those who have preclinical risk factors for cardiovascular diseases are still unclear. The purpose of this study was to evaluate the effect of lifestyle (exercise and diet) modification on measures of left ventricular diastolic filling (LVDF), arterial distensibility (AD), BP (clinic and 24 hour), and exercise capacity (VO2max) in individuals with either high-normal BP (HNBP), impaired fasting glucose level (IFG), or impaired glucose tolerance (IGT). These preliminary findings are from a larger randomized trial of Staged Nutrition and Activity Counseling (SNAC) whose plan includes an individually customized Mediterranean diet with physical exercise, vs usual care lifestyle counseling. Twenty seven subjects with either HNBP, IFG, or IGT (11 M and 16 F, 53.6 ± 7.4 yrs) have participated in the preliminary analysis of the study cohort. Before and after 8 weeks of SNAC, measures of LVDF [early filling flow velocity (E), late filling flow velocity (A), E/A ratio, isovolumic relaxation time (IVRT) and deceleration time (DT)], left ventricular mass (LVM), and AD in carotid (CA) and brachial (BA) arteries assessed using VingMed-5™ cardiac imaging system at rest, and VO2max by exercise treadmill test were determined. Clinic BP using an automated device (BP-TRU™) and 24-h ambulatory BP using a Spacelabs™ ABPM were also recorded. AD in CA improved significantly following SNAC (0.85 ± .28 vs 0.99 ± .28 1/mmHgx10-1, p
Journal of Neuroscience Methods, 2007
The accurate assessment of autonomic sympathetic function is important in the diagnosis and study... more The accurate assessment of autonomic sympathetic function is important in the diagnosis and study of various autonomic and cardiovascular disorders. Sympathetic function in humans can be assessed by recording the muscle sympathetic nerve activity, which is characterized by synchronous neuronal discharges separated by periods of neural silence dominated by colored Gaussian noise. The raw nerve activity is generally rectified, integrated, and quantified using the integrated burst rate or area. We propose an alternative quantification involving spike detection using a two-stage stationary wavelet transform (SWT) de-noising method. The SWT coefficients are first separated into noiserelated and burst-related coefficients on the basis of their local kurtosis. The noise-related coefficients are then used to establish a threshold to identify spikes within the bursts. This method demonstrated better detection performance than an unsupervised amplitude discriminator and similar waveletbased methods when confronted with simulated data of varying burst rate and signal to noise ratio. Additional validation on data acquired during a graded head-up tilt protocol revealed a strong correlation between the mean spike rate and the mean integrate burst rate (r = 0.85) and burst area rate (r = 0.91). In conclusion, the kurtosis-based wavelet de-noising technique is a potentially useful method of studying sympathetic nerve activity in humans.
Journal of Cardiopulmonary Rehabilitation and Prevention, 2009
BACKGROUND AND AIM: There is growing evidence that low-grade systemic inflammation is closely inv... more BACKGROUND AND AIM: There is growing evidence that low-grade systemic inflammation is closely involved in the pathogenesis of type 2 diabetes. The aim of this study was to investigate the relationship between serum inflammatory markers and selected parameters known as risk factors of type 2 diabetes in Korean children. METHODS: In a cross-section study of 263 Korean children aged 12-13 year old, body fatness parameters including height and weight, body mass index (kg/m 2), percent body fat, waist circumference and waist-to-hip ratio were measured using our standardized protocols s. Maximum minute volume of oxygen uptake (VO2max) as an index of cardio/respiratory fitness (CRF) was measured on a motor-driven treadmill using the Bruce protocol. Fasting levels of serum TNF-alpha, interleukin 6, visfatin, retinol binding protein 4, glucose, insulin, TC, HDLC and triglycerides (TG) were also measured using standardized protocols. Pearson's correlations were calculated to assess the relationships between inflammatory markers and selected clinical parameters. RESULTS: Inflammatory markers correlated positively with most of body fatness parameters, resting blood pressure, TC and TG, insulin, and HOMA-IR and negatively with CRF, physical activity, and HDLC. CONCLUSIONS: Serum inflammatory markers were significantly correlated with most of the risk factors implicated in the development of type 2 diabetes. These data provide additional support for the previously reported relationships between subclinical inflammation and the risk of type 2 diabetes in adults.
Journal of Applied Physiology, 2006
Journal of Applied Physiology, 2005
Six male subjects [23 yr (SD 4)] performed repetitions (6–8) of two-legged, moderate-intensity, k... more Six male subjects [23 yr (SD 4)] performed repetitions (6–8) of two-legged, moderate-intensity, knee-extension exercise during two separate protocols that included step transitions from 3 W to 90% estimated lactate threshold (θL) performed as a single step (S3) and in two equal steps (S1, 3 W to ∼45% θL; S2, ∼45% θL to ∼90% θL). The time constants (τ) of pulmonary oxygen uptake (V̇o2), leg blood flow (LBF), heart rate (HR), and muscle deoxygenation (HHb) were greater ( P < 0.05) in S2 (τV̇o2, ∼52 s; τLBF, ∼ 39 s; τHR, ∼42 s; τHHb, ∼33 s) compared with S1 (τV̇o2, ∼24 s; τLBF, ∼21 s; τHR, ∼21 s; τHHb, ∼16 s), while the delay before an increase in HHb was reduced ( P < 0.05) in S2 (∼14 s) compared with S1 (∼20 s). The V̇o2 and HHb amplitudes were greater ( P < 0.05) in S2 compared with S1, whereas the LBF amplitude was similar in S2 and S1. Thus the slowed V̇o2 response in S2 compared with S1 is consistent with a mechanism whereby V̇o2 kinetics is limited, in part, by a slowed...
Journal of Applied Physiology, 2004
Nine healthy volunteers performed a series of single handgrip isometric contractions to test the ... more Nine healthy volunteers performed a series of single handgrip isometric contractions to test the hypothesis that the blood flow response to a contraction is determined solely by the tension-time index (isometric analog of work). Contractions were performed in duplicate at 15, 30, and 60% of maximal voluntary contraction (MVC) at durations of 0.5, 1, and 2 s. Forearm blood flow (FBF) was measured beat by beat by using Doppler ultrasound. Peak FBF responded in a graded fashion to graded increases in peak tension with contraction time held constant (35, 56, and 90 ml/min for 15, 30, and 60% MVC for 1 s, respectively). When tension was kept constant, peak FBF responded in a graded fashion to graded increases in duration (77, 90, and 97 ml/min for 60% MVC for 0.5, 1, and 2 s). With a constant tension-time index, peak FBF responded in a graded fashion to graded increases in peak tension (48, 56, and 77 ml/min for 15% MVC/2 s, 30% MVC/1 s, and 60% MVC/0.5 s). Similar trends were also obser...
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Papers by Kevin Shoemaker