Jerome Dempsey - Academia.edu (original) (raw)

Papers by Jerome Dempsey

Proceedings of the American Thoracic Society, Jan 15, 2008

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is a form of periodic breathing, com... more Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is a form of periodic breathing, commonly observed in patients with heart failure (HF), in which central apneas alternate with hyperpneas that have a waxing-waning pattern of tidal volume. Uniform criteria by which to diagnose a clinically significant degree of CSR-CSA have yet to be established. CSR-CSA is caused by respiratory control system instability characterized by a tendency to hyperventilate. Central apnea occurs when Pa(CO(2)) falls below the threshold for apnea during sleep due to ventilatory overshoot. Patients with CSR-CSA are generally hypocapnic, with a Pa(CO(2)) closer than normal to the apneic threshold such that even slight augmentation in ventilation drives Pa(CO(2)) below threshold and triggers apnea. Factors contributing to hyperventilation in HF include stimulation of pulmonary irritant receptors by pulmonary congestion, increased chemoreceptor sensitivity, reduced cerebrovascular blood flow, and recu...

The Journal of Physiology, 2004

Sleep unmasks a highly sensitive hypocapnia‐induced apnoeic threshold, whereby apnoea is initiate... more Sleep unmasks a highly sensitive hypocapnia‐induced apnoeic threshold, whereby apnoea is initiated by small transient reductions in arterial CO2 pressure (PaCO2) below eupnoea and respiratory rhythm is not restored until PaCO2 has risen significantly above eupnoeic levels. We propose that the ‘CO2 reserve’ (i.e. the difference in PaCO2 between eupnoea and the apnoeic threshold (AT)), when combined with ‘plant gain’ (or the ventilatory increase required for a given reduction in PaCO2) and ‘controller gain’ (ventilatory responsiveness to CO2 above eupnoea) are the key determinants of breathing instability in sleep. The CO2 reserve varies inversely with both plant gain and the slope of the ventilatory response to reduced CO2 below eupnoea; it is highly labile in non‐random eye movement (NREM) sleep. With many types of increases or decreases in background ventilatory drive and PaCO2, the slope of the ventilatory response to reduced PaCO2 below eupnoea remains unchanged from control. Thu...

Journal of Applied Physiology, 2009

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO2 in c... more Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO2 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 Pco2 at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in PaCO2 would narrow the difference between the eupneic PaCO2 and the apneic threshold PaCO2 (ΔPaCO2), known as the CO2 reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO2 by ∼25% below control. The CO2 reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mod...

Journal of Applied Physiology, 2013

We review evidence in support of significant contributions to the pathogenesis of obstructive sle... more 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 neurochemical control of central respiratory motor output through its effects on output stability, upper airway dilator muscle activation, and arousability. In turn, we consider the evidence demonstrating effective treatment of OSA via approaches that address each of these pathophysiologic risk factors. Finally, a case is made for combining treatments aimed at both anatomical and ventilatory control system deficiencies and for individualizing treatment to address a patient 's own specific risk factors.

Journal of Applied Physiology, 2013

To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predic... more To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predict the success of the treatment aimed at stabilization or increase in respiratory motor outputs, we studied 26 newly diagnosed OSA patients [apnea-hypopnea index (AHI) 42 ± 5 events/h with 92% of apneas obstructive] who were treated with O2supplementation, an isocapnic rebreathing system in which CO2was added only during hyperpnea to prevent transient hypocapnia, and a continuous rebreathing system. We also measured each patient's controller gain below eupnea [change in minute volume/change in end-tidal Pco2(ΔV̇e/ΔPetCO2)], CO2reserve (eupnea-apnea threshold PetCO2), and plant gain (ΔPetCO2/ΔV̇e), as well as passive upper airway closing pressure (Pcrit). With isocapnic rebreathing, 14/26 reduced their AHI to 31 ± 6% of control ( P < 0.01) (responder); 12/26 did not show significant change (nonresponder). The responders vs. nonresponders had a greater controller gain (6.5 ± 1.7 vs. ...

Journal of Applied Physiology, 2006

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyp... more To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired Po2. We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78–80%), and hyperoxia (inspired O2 fraction = 50–52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sighlike breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 ± 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 ± 0.8 s; P...

American Journal of Respiratory and Critical Care Medicine, 2002

To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart fai... more To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart failure (CHF), we measured the end-tidal carbon dioxide pressure (P ET CO 2) during spontaneous breathing, the apnea-hypopnea threshold for CO 2 , and then calculated the difference between these two measurements in 19 stable patients with CHF with (12 patients) or without (7 patients) CSA during non-rapid eye movement sleep. Pressure support ventilation was used to reduce the P ET CO 2 and thereby determine the thresholds. In patients with CSA, 1.5-3% CO 2 was supplied temporarily to stabilize breathing before determining the thresholds. Unlike patients without CSA whose eupneic P ET CO 2 increased during sleep (37.7 Ϯ 1.4 mm Hg versus 40.2 Ϯ 1.5 mm Hg, p Ͻ 0.01), patients with CSA showed no rise in P ET CO 2 from wakefulness to sleep (37.5 Ϯ 0.9 mm Hg versus 38.2 Ϯ 1.0 mm Hg, p ϭ 0.2). Patients with CHF and CSA had their eupneic P ET CO 2 closer to the threshold P ET CO 2 than patients without CSA (⌬ P ET CO 2 [eupneic P ET CO 2-threshold P ET CO 2 ] was 2.8 Ϯ 0.3 mm Hg versus 5.1 Ϯ 0.7 mm Hg for apnea, p Ͻ 0.01; 1.7 Ϯ 0.7 versus 4.1 Ϯ 0.5 mm Hg for hypopnea, p Ͻ 0.05). In summary, patients with CHF and CSA neither increase their eupneic P ET CO 2 during sleep nor proportionally decrease their apnea-hypopnea threshold. The resultant narrowed ⌬ P ET CO 2 predisposes the patient to the development of apnea and subsequent breathing instability.

The Journal of Physiology, 2006

Medicine and Science in Sports and Exercise, 1999

Wetter, Thomas J., Craig A. Harms, William B. Nelson, David F. Pegelow, and Jerome A. Dempsey. In... more Wetter, Thomas J., Craig A. Harms, William B. Nelson, David F. Pegelow, and Jerome A. Dempsey. Influence of respiratory muscle work on V O 2 and leg blood flow during submaximal exercise. J. Appl. Physiol. 87(2): 643-651, 1999.-The work of breathing (W b) normally incurred during maximal exercise not only requires substantial cardiac output and O 2 consumption (V O 2) but also causes vasoconstriction in locomotor muscles and compromises leg blood flow (Q leg). We wondered whether the W b normally incurred during submaximal exercise would also reduce Q leg. Therefore, we investigated the effects of changing the W b on Q leg via thermodilution in 10 healthy trained male cyclists [maximal V O 2 (V O 2 max) ϭ 59 Ϯ 9 ml•kg Ϫ1 •min Ϫ1 ] during repeated bouts of cycle exercise at work rates corresponding to 50 and 75% of V O 2 max. Inspiratory muscle work was 1) reduced 40 Ϯ 6% via a proportional-assist ventilator, 2) not manipulated (control), or 3) increased 61 Ϯ 8% by addition of inspiratory resistive loads. Increasing the W b during submaximal exercise caused V O 2 to increase; decreasing the W b was associated with lower V O 2 (⌬V O 2 ϭ 0.12 and 0.21 l/min at 50 and 75% of V O 2 max , respectively, for ϳ100% change in W b). There were no significant changes in leg vascular resistance (LVR), norepinephrine spillover, arterial pressure, or Q leg when W b was reduced or increased. Why are LVR, norepinephrine spillover, and Q leg influenced by the W b at maximal but not submaximal exercise? We postulate that at submaximal work rates and ventilation rates the normal W b required makes insufficient demands for V O 2 and cardiac output to require any cardiovascular adjustment and is too small to activate sympathetic vasoconstrictor efferent output. Furthermore, even a 50-70% increase in W b during submaximal exercise, as might be encountered in conditions where ventilation rates and/or inspiratory flow resistive forces are higher than normal, also does not elicit changes in LVR or Q leg .

Journal of Applied …, 2005

contraction exercise production on locomotor limb venous return during calf Effects of augmented ... more contraction exercise production on locomotor limb venous return during calf Effects of augmented respiratory muscle pressure You might find this additional info useful...

The Journal of Physiology, 2001

The Journal of …, 2001

Our concern in these studies was with the cardiovascular consequences of reflexes from fatiguing ... more Our concern in these studies was with the cardiovascular consequences of reflexes from fatiguing inspiratory muscles in the human. We recently demonstrated that induction of inspiratory muscle fatigue in healthy subjects by means of voluntary hyperpnoea against resistance caused a gradual increase in muscle sympathetic nerve activity (MSNA) in the resting limb (St Croix et al. 2000). This finding, taken together with the finding of increased neural activity in type IV afferents from the diaphragm during fatiguing contractions of this muscle in the anaesthetized rat (Hill,

Rationale: Cerebrovascular reactivity to CO2 provides an important counterregulatorymechanismthat... more Rationale: Cerebrovascular reactivity to CO2 provides an important counterregulatorymechanismthatservestominimizethechangein H at the central chemoreceptor, thereby stabilizing the breathing pattern in the face of perturbations in PaCO2. However, there are no studies relating cerebral circulation abnormality to the presence or absence of central sleep apnea in patients with heart failure. Objectives: To determine whether patients with congestive heart failure and central

Proceedings of the American Thoracic Society, Jan 15, 2008

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is a form of periodic breathing, com... more Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is a form of periodic breathing, commonly observed in patients with heart failure (HF), in which central apneas alternate with hyperpneas that have a waxing-waning pattern of tidal volume. Uniform criteria by which to diagnose a clinically significant degree of CSR-CSA have yet to be established. CSR-CSA is caused by respiratory control system instability characterized by a tendency to hyperventilate. Central apnea occurs when Pa(CO(2)) falls below the threshold for apnea during sleep due to ventilatory overshoot. Patients with CSR-CSA are generally hypocapnic, with a Pa(CO(2)) closer than normal to the apneic threshold such that even slight augmentation in ventilation drives Pa(CO(2)) below threshold and triggers apnea. Factors contributing to hyperventilation in HF include stimulation of pulmonary irritant receptors by pulmonary congestion, increased chemoreceptor sensitivity, reduced cerebrovascular blood flow, and recu...

The Journal of Physiology, 2004

Sleep unmasks a highly sensitive hypocapnia‐induced apnoeic threshold, whereby apnoea is initiate... more Sleep unmasks a highly sensitive hypocapnia‐induced apnoeic threshold, whereby apnoea is initiated by small transient reductions in arterial CO2 pressure (PaCO2) below eupnoea and respiratory rhythm is not restored until PaCO2 has risen significantly above eupnoeic levels. We propose that the ‘CO2 reserve’ (i.e. the difference in PaCO2 between eupnoea and the apnoeic threshold (AT)), when combined with ‘plant gain’ (or the ventilatory increase required for a given reduction in PaCO2) and ‘controller gain’ (ventilatory responsiveness to CO2 above eupnoea) are the key determinants of breathing instability in sleep. The CO2 reserve varies inversely with both plant gain and the slope of the ventilatory response to reduced CO2 below eupnoea; it is highly labile in non‐random eye movement (NREM) sleep. With many types of increases or decreases in background ventilatory drive and PaCO2, the slope of the ventilatory response to reduced PaCO2 below eupnoea remains unchanged from control. Thu...

Journal of Applied Physiology, 2009

Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO2 in c... more Our previous work showed a diminished cerebral blood flow (CBF) response to changes in PaCO2 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 Pco2 at the site of the central chemoreceptors, it may play an important role in maintaining breathing stability. We hypothesized that an attenuated cerebrovascular reactivity to changes in PaCO2 would narrow the difference between the eupneic PaCO2 and the apneic threshold PaCO2 (ΔPaCO2), known as the CO2 reserve, thereby making the subjects more susceptible to apnea. Accordingly, in seven normal subjects, we used indomethacin (Indo; 100 mg by mouth) sufficient to reduce the CBF response to CO2 by ∼25% below control. The CO2 reserve was estimated during non-rapid eye movement (NREM) sleep. The apnea threshold was determined, both with and without Indo, in NREM sleep, in a random order using a ventilator in pressure support mod...

Journal of Applied Physiology, 2013

We review evidence in support of significant contributions to the pathogenesis of obstructive sle... more 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 neurochemical control of central respiratory motor output through its effects on output stability, upper airway dilator muscle activation, and arousability. In turn, we consider the evidence demonstrating effective treatment of OSA via approaches that address each of these pathophysiologic risk factors. Finally, a case is made for combining treatments aimed at both anatomical and ventilatory control system deficiencies and for individualizing treatment to address a patient 's own specific risk factors.

Journal of Applied Physiology, 2013

To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predic... more To determine how the obstructive sleep apnea (OSA) patient's pathophysiological traits predict the success of the treatment aimed at stabilization or increase in respiratory motor outputs, we studied 26 newly diagnosed OSA patients [apnea-hypopnea index (AHI) 42 ± 5 events/h with 92% of apneas obstructive] who were treated with O2supplementation, an isocapnic rebreathing system in which CO2was added only during hyperpnea to prevent transient hypocapnia, and a continuous rebreathing system. We also measured each patient's controller gain below eupnea [change in minute volume/change in end-tidal Pco2(ΔV̇e/ΔPetCO2)], CO2reserve (eupnea-apnea threshold PetCO2), and plant gain (ΔPetCO2/ΔV̇e), as well as passive upper airway closing pressure (Pcrit). With isocapnic rebreathing, 14/26 reduced their AHI to 31 ± 6% of control ( P < 0.01) (responder); 12/26 did not show significant change (nonresponder). The responders vs. nonresponders had a greater controller gain (6.5 ± 1.7 vs. ...

Journal of Applied Physiology, 2006

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyp... more To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired Po2. We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78–80%), and hyperoxia (inspired O2 fraction = 50–52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sighlike breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 ± 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 ± 0.8 s; P...

American Journal of Respiratory and Critical Care Medicine, 2002

To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart fai... more To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart failure (CHF), we measured the end-tidal carbon dioxide pressure (P ET CO 2) during spontaneous breathing, the apnea-hypopnea threshold for CO 2 , and then calculated the difference between these two measurements in 19 stable patients with CHF with (12 patients) or without (7 patients) CSA during non-rapid eye movement sleep. Pressure support ventilation was used to reduce the P ET CO 2 and thereby determine the thresholds. In patients with CSA, 1.5-3% CO 2 was supplied temporarily to stabilize breathing before determining the thresholds. Unlike patients without CSA whose eupneic P ET CO 2 increased during sleep (37.7 Ϯ 1.4 mm Hg versus 40.2 Ϯ 1.5 mm Hg, p Ͻ 0.01), patients with CSA showed no rise in P ET CO 2 from wakefulness to sleep (37.5 Ϯ 0.9 mm Hg versus 38.2 Ϯ 1.0 mm Hg, p ϭ 0.2). Patients with CHF and CSA had their eupneic P ET CO 2 closer to the threshold P ET CO 2 than patients without CSA (⌬ P ET CO 2 [eupneic P ET CO 2-threshold P ET CO 2 ] was 2.8 Ϯ 0.3 mm Hg versus 5.1 Ϯ 0.7 mm Hg for apnea, p Ͻ 0.01; 1.7 Ϯ 0.7 versus 4.1 Ϯ 0.5 mm Hg for hypopnea, p Ͻ 0.05). In summary, patients with CHF and CSA neither increase their eupneic P ET CO 2 during sleep nor proportionally decrease their apnea-hypopnea threshold. The resultant narrowed ⌬ P ET CO 2 predisposes the patient to the development of apnea and subsequent breathing instability.

The Journal of Physiology, 2006

Medicine and Science in Sports and Exercise, 1999

Wetter, Thomas J., Craig A. Harms, William B. Nelson, David F. Pegelow, and Jerome A. Dempsey. In... more Wetter, Thomas J., Craig A. Harms, William B. Nelson, David F. Pegelow, and Jerome A. Dempsey. Influence of respiratory muscle work on V O 2 and leg blood flow during submaximal exercise. J. Appl. Physiol. 87(2): 643-651, 1999.-The work of breathing (W b) normally incurred during maximal exercise not only requires substantial cardiac output and O 2 consumption (V O 2) but also causes vasoconstriction in locomotor muscles and compromises leg blood flow (Q leg). We wondered whether the W b normally incurred during submaximal exercise would also reduce Q leg. Therefore, we investigated the effects of changing the W b on Q leg via thermodilution in 10 healthy trained male cyclists [maximal V O 2 (V O 2 max) ϭ 59 Ϯ 9 ml•kg Ϫ1 •min Ϫ1 ] during repeated bouts of cycle exercise at work rates corresponding to 50 and 75% of V O 2 max. Inspiratory muscle work was 1) reduced 40 Ϯ 6% via a proportional-assist ventilator, 2) not manipulated (control), or 3) increased 61 Ϯ 8% by addition of inspiratory resistive loads. Increasing the W b during submaximal exercise caused V O 2 to increase; decreasing the W b was associated with lower V O 2 (⌬V O 2 ϭ 0.12 and 0.21 l/min at 50 and 75% of V O 2 max , respectively, for ϳ100% change in W b). There were no significant changes in leg vascular resistance (LVR), norepinephrine spillover, arterial pressure, or Q leg when W b was reduced or increased. Why are LVR, norepinephrine spillover, and Q leg influenced by the W b at maximal but not submaximal exercise? We postulate that at submaximal work rates and ventilation rates the normal W b required makes insufficient demands for V O 2 and cardiac output to require any cardiovascular adjustment and is too small to activate sympathetic vasoconstrictor efferent output. Furthermore, even a 50-70% increase in W b during submaximal exercise, as might be encountered in conditions where ventilation rates and/or inspiratory flow resistive forces are higher than normal, also does not elicit changes in LVR or Q leg .

Journal of Applied …, 2005

contraction exercise production on locomotor limb venous return during calf Effects of augmented ... more contraction exercise production on locomotor limb venous return during calf Effects of augmented respiratory muscle pressure You might find this additional info useful...

The Journal of Physiology, 2001

The Journal of …, 2001

Our concern in these studies was with the cardiovascular consequences of reflexes from fatiguing ... more Our concern in these studies was with the cardiovascular consequences of reflexes from fatiguing inspiratory muscles in the human. We recently demonstrated that induction of inspiratory muscle fatigue in healthy subjects by means of voluntary hyperpnoea against resistance caused a gradual increase in muscle sympathetic nerve activity (MSNA) in the resting limb (St Croix et al. 2000). This finding, taken together with the finding of increased neural activity in type IV afferents from the diaphragm during fatiguing contractions of this muscle in the anaesthetized rat (Hill,

Rationale: Cerebrovascular reactivity to CO2 provides an important counterregulatorymechanismthat... more Rationale: Cerebrovascular reactivity to CO2 provides an important counterregulatorymechanismthatservestominimizethechangein H at the central chemoreceptor, thereby stabilizing the breathing pattern in the face of perturbations in PaCO2. However, there are no studies relating cerebral circulation abnormality to the presence or absence of central sleep apnea in patients with heart failure. Objectives: To determine whether patients with congestive heart failure and central