Jerome A Dempsey

• University of Wisconsin–Madison

We tested the hypothesis that breathing heliox, to attenuate the mechanical constraints accompanying the decline in pulmonary function with aging, improves exercise performance. Fourteen endurance-trained older men (67.9 ± 5.9 year, \(\dot{V}\)O2max: 50.8 ± 5.8 ml/kg/min; 151% predicted) completed two cycling 5-km time trials while breathing room a...

We have examined the importance of three long‐standing questions concerning chemoreceptor influences on cardiorespiratory function which are currently experiencing a resurgence of study among physiologists and clinical investigators. Firstly, while carotid chemoreceptors (CB) are required for hypoxic stimulation of breathing, use of an isolated, ex...

Nearly forty years ago, Professor Dempsey delivered the 1985 ACSM Joseph B. Wolffe Memorial Lecture titled: "Is the lung built for exercise?". Since then, much experimental work has been directed at enhancing our understanding of the functional capacity of the respiratory system by applying complex methodologies to the study of exercise. This revie...

Substantial advances have been made recently into the discovery of fundamental mechanisms underlying the neural control of breathing and even some inroads into translating these findings to treating breathing disorders. Here, we review several of these advances, starting with an appreciation of the importance of V̇A:V̇CO2:PaCO2 relationships, then...

Physical activity is the most common source of heat strain for humans. The thermal strain of physical activity causes over-breathing (hyperventilation) and this has adverse physiological repercussions. The mechanisms underlying heat-induced hyperventilation during exercise are unknown, but recent evidence supports a primary role of carotid body hyp...

Humans hyperventilate under heat and cold strain. This hyperventilatory response has detrimental consequences including acid–base dysregulation, dyspnoea, decreased cerebral blood flow and accelerated brain heating. The ventilatory response to hypoxia is exaggerated under whole‐body heating and cooling, indicating that altered carotid body function...

Increased ventilation relative to metabolic secondary to alveolar hyperventilation and/or increased physiological dead space (excess ventilation) is a key cause of exertional dyspnoea. Excess ventilation has assumed a prominent role in the functional assessment of patients with heart failure (HF) with reduced (r) or preserved (p) ejection fraction,...

In health, the near-eucapnic, highly efficient hyperpnea during mild-to-moderate intensity exercise is driven by three obligatory contributions, namely, feedforward central command from supra-medullary locomotor centers, feedback from limb muscle afferents, and respiratory CO2 exchange (V̇CO2). Inhibiting each of these stimuli during exercise elici...

A model of optimal control of ventilation recently developed for humans has suggested that the localization of the transition between a convective and a diffusive transport of the respiratory gas determines how ventilation should be controlled to minimize its energetic cost at any metabolic regime. We generalized this model to any mammal, based on...

figure legend Genesis of air hunger. In a working model of mechanisms giving rise to air hunger, brainstem respiratory centres send projections (corollary discharge) to the forebrain, giving rise to breathing discomfort in proportion to the magnitude of corollary discharge (Banzett et al., 2021 in press). These brainstem respiratory centres also se...

Key points The carotid chemoreceptor mediates the ventilatory and muscle sympathetic nerve activity (MSNA) responses to hypoxia and contributes to tonic sympathetic and respiratory drives. It is often presumed that both excitatory and inhibitory tests of chemoreflex function show congruence in the end‐organ responses. Ventilatory and neurocirculato...

In the healthy, untrained young adult a case is made for a respiratory system- airways, pulmonary vasculature, lung parenchyma, respiratory muscles and neural ventilatory control system - which is near ideally designed to ensure a highly efficient, homeostatic response to exercise of varying intensities and durations. Our aim was then to consider c...

This viewpoint is the result of a Horizon Round Table discussion of Exercise and Aging held during the 2017 Saltin International Graduate School in Exercise and Clinical Physiology in Gatineau, Quebec. This expert panel discussed key issues and approaches to future research into aging, across human physiological systems, current societal concerns,...

Central sleep apnea is prevalent in patients with heart failure, healthy individuals at high altitudes, and chronic opiate users and in the initiation of “mixed” (that is, central plus obstructive apneas). This brief review focuses on (a) the causes of repetitive, cyclical central apneas as mediated primarily through enhanced sensitivities in the r...

We examine recent findings that have revealed interdependence of function within the chemoreceptor pathway regulating breathing and sympathetic vasomotor activity and the hypersensitization of these reflexes in chronic disease states. Recommendations are made as to how these states of hyperreflexia in chemoreceptors and muscle afferents might be mo...

We examine 2 means by which the healthy respiratory system contributes to exercise limitation. These include the activation of respiratory and locomotor muscle afferent reflexes, which constrain blood flow and hasten fatigue in both sets of muscles, and the excessive increases in pulmonary vascular pressures at high cardiac outputs, which constrain...

Sympathetically-induced vasoconstrictor modulation of local vasodilation occurs in contracting skeletal muscle during exercise to ensure appropriate perfusion of a large active muscle mass and to also maintain arterial blood pressure. In this synthesis, we discuss the contribution of group III-IV muscle afferents to the sympathetic modulation of bl...

Objective: This article reviews the current engineering approaches for the detection and treatment of sleep apnea. Approach: It discusses signal acquisition and processing, highlights the current nonsurgical and nonpharmacological treatments, and discusses potential new therapeutic approaches. Main results: This work has led to an array of val...

The biological responses to acute and chronic exercise are marked by a high level of physiological redundancy that operates at various levels of integration, including the molecular, cellular, organ-system, and whole-body scale. During acute exercise, this redundancy protects whole-body homeostasis in the face of 10-fold or more increases in whole-...

We present the device design, simulation, and measurement results of a therapy device that potentially prevents sleep apnea by slightly increasing inspired CO2 through added dead space (DS). The rationale for treatment of sleep apnea with CO2 manipulation is based on two recently reported premises: (i) preventing transient reductions in PaCO2 will...

Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal...

Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal...

We recently hypothesized that across the range of normoxia to severe hypoxia the major determinant of central motor drive (CMD) during endurance exercise switches from a predominantly peripheral origin to a hypoxic-sensitive central component of fatigue. We found that peripheral locomotor muscle fatigue (pLMF) is the prevailing factor limiting cent...

We address adaptive vs. maladaptive responses to hypoxemia in healthy humans and hypoxic-tolerant species during wakefulness, sleep, and exercise. Types of hypoxemia discussed include short-term and life-long residence at high altitudes, the intermittent hypoxemia attending sleep apnea, or training regimens prescribed for endurance athletes. We pro...

We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO2 . The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body PCO2 ≈ 22, 41 and 68 mmHg, respectively) on the ventilatory CO2 sensitivity of central chemoreceptors was studied in seven awake dogs...

to the editor: Many thanks to Dr. Joseph ([1][1]) for requesting clarification of methods used to measure metabolic rate of the rodent in our recent study ([3][2]). Measurements of V̇o2 and V̇co2 in the rat do indeed require a great deal of precision, given that the differences between inspired

We evaluated several methods for characterizing hypoxic chemosensitivity in the conscious rat. Adult Sprague-Dawley rats (n=30) were exposed to normobaric hypoxia (FIO2, 0.15, 0.12, and 0.09). We measured ventilation (VE; barometric plethysmography), arterial oxygen saturation (SpO2; pulse oximeter), and oxygen consumption and carbon dioxide produc...

I received most of my education in Canada, finishing at the University of Wisconsin (UW)-Madison medical school, where I have remained throughout my academic career. The research in our laboratory centered on the broad field of respiratory and cardiorespiratory physiology and pathophysiology as applied to exercise, sleep, hypoxia, and several chron...

We review the substantial recent progress made in understanding the underlying mechanisms controlling breathing and the applicability of these findings to selected human diseases. Emphasis is placed on the sites of central respiratory rhythm and pattern generation as well as newly described functions of the carotid chemoreceptors, the integrative n...

We have shown previously that inhibition of the isolated carotid body (CB) chemoreceptor (via CB‐specific hyperoxia & hypocapnia) markedly reduced the ventilatory response sensitivity of the central chemoreceptors to increased PaCO2 whereas stimulation (via CB‐specific hypoxia & normocapnia) markedly increased it (Blain et al., J. Physiol. 588: 245...

Sustained high-intensity exercise demands time-dependent increases in ventilation and respiratory muscle work. Exercise-induced diaphragmatic fatigue commonly occurs because of a combination of the amount of diaphragmatic work required to support the exercise hyperpnea plus the increased propensity of the diaphragm for fatigue during exercise when...

During sojourn to high altitudes progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes including: a) correction of alkalinity in cerebrospinal fluid; b) increased...

We review evidence in support of significant contributions to the pathogenesis of obstructive sleep apnea (OSA) from pathophysiological factors beyond the well-accepted importance of airway anatomy. Emphasis is placed on contributions from neuro-chemical control of central respiratory motor output through its effects on output stability, upper airw...

When tested in isolation, stimuli associated with respiratory CO2 exchange, feedforward central command and type III-IV muscle afferent feedback have each been shown to be capable of eliciting exercise-like cardio-ventilatory responses - but their relative contributions in a setting of physiologic exercise remains controversial. We reasoned that in...

This essay is simply a highly personal account of how one mentor has joined with a team of mentors, combined with special "permanent" employees, lively group interactions and high expectations for trainees to provide a fertile environment for the training of scientists. I also need to acknowledge the deep personal friendships that have developed an...

Neurophysiologically, central apnea is due to a temporary failure in the pontomedullary pacemaker generating breathing rhythm. As a polysomnographic finding, central apneas occur in many pathophysiological conditions. Depending on the cause or mechanism, central apneas may not be clinically significant, for example, those that occur normally at sle...

To determine how the OSA patient's pathophysiologic traits predict the success of the treatment aimed at stabilization or increase in respiratory motor outputs, we studied 26 patients with OSA (AHI 42±5 events/hour with 92% of apnea were obstructive), who were treated with O2 supplementation, an isocapnic rebreathing system in which CO2 was added o...

In patients with hypertension, volitional slowing of the respiratory rate has been purported to reduce arterial pressure via withdrawal of sympathetic tone. We examined the effects of paced breathing at 7, 14, and 21 breaths per minute, with reciprocal changes in tidal volume, on muscle sympathetic nerve activity, forearm blood flow, forearm vascul...

Background In patients with hypertension, volitional slowing of the respiratory rate has been purported to reduce arterial pressure via withdrawal of sympathetic tone. Methods We examined the effects of paced breathing at 7, 14, and 21 breaths per minute with reciprocal changes in tidal volume, on blood pressure, muscle sympathetic nerve activity,...

Neurophysiologically, central apnea is due to a temporary failure in the pontomedullary pacemaker generating breathing rhythm. As a polysomnographic finding, central apneas occur in many pathophysiological conditions. Depending on the cause or mechanism, central apneas may not be clinically significant, for example, those that occur normally at sle...

Unstable periodic breathing with intermittent ventilatory overshoots and undershoots commonly occurs in chronic heart failure, in hypoxia, with chronic opioid use and in certain types of obstructive sleep apnea. Sleep promotes breathing instability because it unmasks a highly sensitive dependence of the respiratory control system on chemoreceptor i...

Abstract  The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward 'central command' mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types...

During exercise by healthy mammals, alveolar ventilation and alveolar-capillary diffusion increase in proportion to the increase in metabolic rate to prevent PaCO2 from increasing and PaO2 from decreasing. There is no known mechanism capable of directly sensing the rate of gas exchange in the muscles or the lungs; thus, for over a century there has...

summary Te respiratory system contributes in three major ways to limitations in arterial O 2 content and/or blood flow during high-intensity exercise, namely: 1) exercise-induced arterial hypoxemia (EIAH) which occurs to a highly variable extent among highly trained male and female runners; 2) intrathoracic pressure effects on stroke volume; and 3)...

During exercise by healthy mammals, alveolar ventilation and alveolar‐capillary diffusion increase in proportion to the increase in metabolic rate to prevent PaCO 2 from increasing and Pa o 2 from decreasing. There is no known mechanism capable of directly sensing the rate of gas exchange in the muscles or the lungs; thus, for over a century there...

Non‐Technical Summary We investigated the influence of group III/IV muscle afferents on central motor drive, the development of peripheral locomotor muscle fatigue, and endurance performance time during high‐intensity constant‐load cycling exercise to exhaustion. Our findings suggest that, on the one hand, afferent feedback ensures adequate circula...

Greetings to the Journal of Applied Physiology readership. This editorial will be the last report submitted by our current editorial team, which began their service on July 1st of 2005 and will terminate June 30, 2011. I will concentrate on the scope, quality, and impact of the Journal of Applied

To compare the breathing instability and upper airway collapsibility between patients with pure OSA (i.e. 100% of apneas are obstructive) and patients with predominant OSA (i.e., coexisting obstructive and central apneas). A cross-sectional study with data scored by a fellow being blinded to the subjects' classification. The results were compared b...

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to the editor: Our interpretation of Dr. White's letter ([10][1]) is that he pretty much agrees that our findings suggest that thin-fiber muscle afferents in the human are significantly involved in the cardiovascular and ventilatory responses to rhythmic exercise ([1][2]) and one of the possible

The sections in this article are:

The sections in this article are:

We investigated the role of somatosensory feedback on cardioventilatory responses to rhythmic exercise in five men. In a double-blind, placebo-controlled design, subjects performed the same leg cycling exercise (50/100/150/325 ± 19 W, 3 min each) under placebo conditions (interspinous saline, L(3)-L(4)) and with lumbar intrathecal fentanyl impairin...

We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO2 . The effect of CB normoxic hypocapnia, normocapnia, and hypercapnia (PCB CO2 ≈ 22, 41, & 68 mmHg) on the ventilatory CO2 sensitivity of central chemoreceptors was studied in 7 awake dogs with vascularly-isolated and...

We examined the effects of respiratory muscle work [inspiratory (W r-insp); expiratory (Wr-exp)] and arterial oxygenation (SpO2) on exercise-nduced locomotor muscle fatigue in patients with chronic obstructive pulmonary disease (COPD). Eight patients (FEV, 48 ± 4%) performed constant-load cycling to exhaustion (Ctrl; 9.8 ± 1.2 min). In subsequent t...

We assessed the contribution of carotid body chemoreceptors (CB) to the ventilatory response to specific CNS hypercapnia in the unanesthetized awake dog. We used extracorporeal blood perfusion of the reversibly isolated carotid sinus to maintain normal blood gases (normoxic, normocapnic perfusate) at the CB, to inhibit the CB (hyperoxic, hypocapnic...

In this review we discuss the implications for ventilatory control of newer evidence suggesting that central and peripheral chemoreceptors are not functionally separate but rather that they are dependent upon one another such that the sensitivity of the medullary chemoreceptors is critically determined by input from the carotid body chemoreceptors...

Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anatomically compromised, collapsible airway, the sleep-induced loss of compensatory tonic input to the upper airway dilator muscle motor neurons leads to co...

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Untreated sleep apnea is a prevalent but treatable condition of breathing pauses during sleep. With approximately 15% of the US population affected, understanding of the total health burden is necessary to guide policy, population initiatives, and clinical practice to reduce the prevalence of this condition. To outline the history and need for a po...

Control of exercising muscle blood flow is a balance between local vasodilatory factors and the increase in global sympathetic vasoconstrictor outflow. Hypoxia has been shown to potentiate the muscle sympathetic nerve response to exercise, potentially limiting the increase in muscle blood flow. Accordingly, we investigated sympathetic restraint to...

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in Pa(CO(2)) in congestive heart failure patients with central sleep apnea compared with those without apnea. Since the regulation of CBF serves to minimize oscillations in H(+) and Pco(2) at the site of the central chemoreceptors, it may play an important role in m...

We used extracorporeal perfusion of the reversibly isolated carotid sinus region to determine the effects of specific carotid body (CB) chemoreceptor inhibition on eupneic ventilation (Vi) in the resting, awake, intact dog. Four female spayed dogs were studied during wakefulness when CB was perfused with 1) normoxic, normocapnic blood; and 2) hyper...

We investigated the role of somatosensory feedback from locomotor muscles on central motor drive (CMD) and the development of peripheral fatigue during high-intensity endurance exercise. In a double-blind, placebo-controlled design, eight cyclists randomly performed three 5 km time trials: control, interspinous ligament injection of saline (5K(Plac...

This review addresses three types of causes of respiratory system limitations to O(2) transport and exercise performance that are experienced by significant numbers of active, highly fit younger and older adults. First, flow limitation in intrathoracic airways may occur during exercise because of narrowed, hyperactive airways or secondary to excess...

We investigated whether somatosensory feedback from contracting limb muscles exerts an inhibitory influence on the determination of central command during closed-loop cycling exercise in which the subject voluntarily determines his second-by-second central motor drive. Eight trained cyclists performed two 5-km time trials either without (5K(Ctrl))...

Basic responses to exerciseDoes the pulmonary system fail and, if so, do failures contribute to limitations of endurance performance?Effects of endurance training on the pulmonary systemDoes specific respiratory muscle training improve endurance performance?Mechanisms for improvement in endurance perf onnanceConclusions References

We briefly summarize recent evidence pertaining to how mechanisms primarily under the control of the respiratory system-namely, arterial oxyhemoglobin desaturation, respiratory muscle work and fatigue, and cyclical fluctuations in intrathoracic pressure-may contribute to exercise limitation. Respiratory influences on cardiac output and on sympathet...

Recently, we have shown that specific, transient carotid chemoreceptor (CC) inhibition in exercising dogs causes vasodilatation in limb muscle. The purpose of the present investigation was to determine if CC suppression reduces muscle sympathetic nerve activity (MSNA) in exercising humans. Healthy subjects (N = 7) breathed hyperoxic gas (F(IO(2)) a...

We assessed the contribution of carotid chemoreceptors tonic activity (CC) on control of eupnea and on the ventilatory response to brain hypoxia and hyperoxia in the unanesthetized awake dog. We used extracorporeal blood perfusion of the reversibly isolated carotid sinus to maintain normal (normoxic, normocapnic perfusate) or to inhibit (hyperoxic,...

The concept of peripheral locomotor muscle fatigue as a regulated variable.

In healthy subjects, heavy intensity endurance exercise places substantial demands on the respiratory muscles as breathing frequency, ventilation and the work of breathing rise over time. In the highly trained subject working at high absolute work rates, the ventilatory demand often causes varying degrees of expiratory flow limitation, sometimes ac...

We asked whether the central effects of fatiguing locomotor muscle fatigue exert an inhibitory influence on central motor drive to regulate the total degree of peripheral fatigue development. Eight cyclists performed constant-workload prefatigue trials (a) to exhaustion (83% of peak power output (W(peak)), 10 +/- 1 min; PFT(83%)), and (b) for an id...