Carotid body denervation eliminates apnea in response to transient hypocapnia

2003 ◽  
Vol 94 (1) ◽  
pp. 155-164 ◽  
Author(s):  
Hideaki Nakayama ◽  
Curtis A. Smith ◽  
Joshua R. Rodman ◽  
James B. Skatrud ◽  
Jerome A. Dempsey
Keyword(s):  
Mechanical Ventilation ◽  
Tidal Volume ◽  
Eye Movement ◽  
Carotid Body ◽  
Pressure Support ◽  
Intact Animal ◽  
Periodic Breathing ◽  
Rapid Eye Movement Sleep ◽  
Peripheral Chemoreceptor ◽  
End Tidal

We determined the effects on breathing of transient ventilatory overshoots and concomitant hypocapnia, as produced by pressure support mechanical ventilation (PSV), in intact and carotid body chemoreceptor denervated (CBX) sleeping dogs. In the intact dog, PSV-induced transient increases in tidal volume and hypocapnia caused apnea within 10–11 s, followed by repetitive two-breath clusters separated by apneas, i.e., periodic breathing (PB). After CBX, significant expiratory time prolongation did not occur until after 30 s of PSV-induced hypocapnia, and PB never occurred. Average apneas of 8.4 ± 1-s duration after a ventilatory overshoot required a decrease below eupnea of end-tidal Pco 2 5.1 ± 0.4 Torr below eupnea in the intact animal and 10.1 ± 2 Torr in the CBX dog, where the former reflected peripheral and the latter central dynamic CO2 chemoresponsiveness, as tested in the absence of peripheral chemoreceptor input. Hyperoxia when the dogs were intact shortened PSV-induced apneas and reduced PB but did not mimic the effects of CBX. We conclude that, during non-rapid eye movement sleep, carotid chemoreceptors are required to produce apneas that normally occur after a transient ventilatory overshoot and for PB.

Increased propensity for apnea via dopamine-induced carotid body inhibition in sleeping dogs

2005 ◽  
Vol 98 (5) ◽  
pp. 1732-1739 ◽  
Author(s):  
Bruno J. Chenuel ◽  
Curtis A. Smith ◽  
Kathleen S. Henderson ◽  
Jerome A. Dempsey
Keyword(s):  
Steady State ◽  
Carotid Body ◽  
Pressure Support Ventilation ◽  
Pressure Support ◽  
Ventilatory Response ◽  
Rapid Eye Movement Sleep ◽  
The Difference ◽  
End Tidal ◽  
Carotid Body Chemoreceptors

We determined the effects of specific carotid body chemoreceptor inhibition on the propensity for apnea during sleep. We reduced the responsiveness of the carotid body chemoreceptors using intravenous dopamine infusions during non-rapid eye movement sleep in six dogs. Then we quantified the difference in end-tidal Pco2 (PetCO2) between eupnea and the apneic threshold, the “CO2 reserve,” by gradually reducing PetCO2 transiently with pressure support ventilation at progressively increased tidal volume until apnea occurred. Dopamine infusions decreased steady-state eupneic ventilation by 15 ± 6%, causing a mean CO2 retention of 3.9 ± 1.9 mmHg and a brief period of ventilatory instability. The apneic threshold PetCO2 rose 5.1 ± 1.9 Torr; thus the CO2 reserve was narrowed from −3.9 ± 0.62 Torr in control to −2.7 ± 0.78 Torr with dopamine. This decrease in the CO2 reserve with dopamine resulted solely from the 20.5 ± 11.3% increase in plant gain; the slope of the ventilatory response to CO2 below eupnea was unchanged from normal. We conclude that specific carotid chemoreceptor inhibition with dopamine increases the propensity for apnea during sleep by narrowing the CO2 reserve below eupnea. This narrowing is due solely to an increase in plant gain as the slope of the ventilatory response to CO2 below eupnea was unchanged from normal control. These findings have implications for the role of chemoreceptor inhibition/stimulation in the genesis of apnea and breathing periodicity during sleep.

scholarly journals Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep

2006 ◽  
Vol 100 (1) ◽  
pp. 171-177 ◽  
Author(s):  
Ailiang Xie ◽  
James B. Skatrud ◽  
Dominic S. Puleo ◽  
Jerome A. Dempsey
Keyword(s):  
Mechanical Ventilation ◽  
Time Course ◽  
Pressure Support ◽  
Ventilatory Response ◽  
Relative Activity ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
The Difference ◽  
End Tidal ◽  
Different Levels

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 < 0.05), whereas hyperoxia prolonged it (71.5 ± 13.8 s; P < 0.01). The apneic threshold end-tidal Pco2 (PetCO2) was defined as the PetCO2 at the onset of apnea. During hypoxia, the apneic threshold PetCO2 was higher (38.9 ± 1.7 Torr; P < 0.01) compared with normoxia (35.8 ± 1.1; Torr); during hyperoxia, it was lower (33.0 ± 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic PetCO2 and apneic threshold PetCO2 was smaller during hypoxia (3.0 ± 1.0 Torr P < 001) and greater during hyperoxia (10.6 ± 0.8 Torr; P < 0.05) compared with normoxia (8.0 ± 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic PetCO2 was increased by hypoxia (3.44 ± 0.63 l·min−1·Torr−1; P < 0.05) and decreased by hyperoxia (0.63 ± 0.04 l·min−1·Torr−1; P < 0.05) compared with normoxia (0.79 ± 0.05 l·min−1·Torr−1). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.

scholarly journals Patient-Ventilator Synchrony and Tidal Volume Variability using NAVA and Pressure Support Mechanical Ventilation Modes

2011 ◽  
Vol 44 (1) ◽  
pp. 569-574
Author(s):  
Katherine T. Moorhead ◽  
Lise Piquilloud ◽  
Bernard Lambermont ◽  
Jean Roeseler ◽  
J. Geoffrey Chase ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Tidal Volume ◽  
Pressure Support ◽  
Ventilation Modes ◽  
Ventilator Synchrony

Postnatal maturation of peripheral chemoreceptor ventilatory response to O2 and CO2 in newborn lambs

1996 ◽  
Vol 80 (6) ◽  
pp. 1928-1933 ◽  
Author(s):  
E. Canet ◽  
I. Kianicka ◽  
J. P. Praud
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Time Frame ◽  
Peripheral Chemoreceptor ◽  
Postnatal Maturation ◽  
Time Courses ◽  
End Tidal ◽  
Peripheral Chemoreflex ◽  
End Tidal Co2

Although studies on lambs have shown that carotid body sensitivity to O2 is reset postnatally, it is still unknown whether O2 and CO2 peripheral chemoreflexes undergo parallel postnatal maturation. The present study was designed to analyze maturation of O2 and CO2 peripheral chemoreflexes in 10 lambs at < 24 h and at 12 days of age. We measured the ventilatory (VE) response to three tidal breaths of pure N2 or 13% CO2 in air. Overall, the N2 peripheral chemoreflex increased significantly with maturation [VE/end-tidal O2 (ml.min-1.kg-1.Torr-1) = 2.94 +/- 0.91 at < 24 h vs. 5.13 +/- 0.59 at 12 days, P < 0.05], whereas the CO2 peripheral chemoreflex did not change (VE/end-tidal CO2 = 7.04 +/- 0.98 at < 24 h vs. 7.75 +/- 1.07 at 12 days, not significant). We conclude that the CO2 peripheral chemoreflex does not change in awake lambs within the time frame studied, in contrast to a marked postnatal maturation of the O2 peripheral chemoreflex. The different time courses of O2 and CO2 peripheral chemoreflex maturation support the concept that carotid body sensitivities to O2 and CO2 do not depend on the same basic mechanisms.

Determinants of poststimulus potentiation in humans during NREM sleep

1992 ◽  
Vol 73 (5) ◽  
pp. 1958-1971 ◽  
Author(s):  
M. S. Badr ◽  
J. B. Skatrud ◽  
J. A. Dempsey
Keyword(s):  
Eye Movement ◽  
Control Period ◽  
Periodic Breathing ◽  
Nrem Sleep ◽  
Normal Subjects ◽  
Central Apnea ◽  
Inhibitory Effects ◽  
Arterial Pco2 ◽  
End Tidal ◽  
Sustained Hypoxia

To test whether active hyperventilation activates the “afterdischarge” mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.

scholarly journals Susceptibility to periodic breathing with assisted ventilation during sleep in normal subjects

1998 ◽  
Vol 85 (5) ◽  
pp. 1929-1940 ◽  
Author(s):  
Sonia Meza ◽  
Manuel Mendez ◽  
Michele Ostrowski ◽  
Magdy Younes
Keyword(s):  
Airway Pressure ◽  
Stepwise Regression ◽  
Pressure Support ◽  
Amplification Factor ◽  
Periodic Breathing ◽  
Normal Subjects ◽  
Assisted Ventilation ◽  
The Subject ◽  
Central Apneas ◽  
End Tidal

Assisted ventilation with pressure support (PSV) or proportional assist (PAV) ventilation has the potential to produce periodic breathing (PB) during sleep. We hypothesized that PB will develop when PSV level exceeds the product of spontaneous tidal volume (Vt) and elastance (Vt sp ⋅ E) but that the actual level at which PB will develop [PSV(PB)] will be influenced by the[Formula: see text] (difference between eupneic[Formula: see text] and CO2 apneic threshold) and by ΔRR [response of respiratory rate (RR) to PSV]. We also wished to determine the PAV level at which PB develops to assess inherent ventilatory stability in normal subjects. Twelve normal subjects underwent polysomnography while connected to a PSV/PAV ventilator prototype. Level of assist with either mode was increased in small steps (2–5 min each) until PB developed or the subject awakened. End-tidal [Formula: see text], Vt, RR, and airway pressure (Paw) were continuously monitored, and the pressure generated by respiratory muscle (Pmus) was calculated. The pressure amplification factor (PAF) at the highest PAV level was calculated from [(ΔPaw + Pmus)/Pmus], where ΔPaw is peak Paw − continuous positive airway pressure. PB with central apneas developed in 11 of 12 subjects on PSV. [Formula: see text]ranged from 1.5 to 5.8 Torr. Changes in RR with PSV were small and bidirectional (+1.1 to −3.5 min−1). With use of stepwise regression, PSV(PB) was significantly correlated with Vt sp( P = 0.001), E ( P = 0.00009),[Formula: see text]( P = 0.007), and ΔRR ( P = 0.006). The final regression model was as follows: PSV(PB) = 11.1 Vt sp + 0.3E − 0.4 [Formula: see text] − 0.34 ΔRR − 3.4 ( r = 0.98). PB developed in five subjects on PAV at amplification factors of 1.5–3.4. It failed to occur in seven subjects, despite PAF of up to 7.6. We conclude that 1) a[Formula: see text] apneic threshold exists during sleep at 1.5–5.8 Torr below eupneic[Formula: see text], 2) the development of PB during PSV is entirely predictable during sleep, and 3) the inherent susceptibility to PB varies considerably among normal subjects.

Breath-by-breath respiratory timing and volume control during periodic breathing

1989 ◽  
Vol 257 (3) ◽  
pp. R653-R660
Author(s):  
D. W. Carley ◽  
C. Maayan ◽  
J. Grimes ◽  
D. C. Shannon
Keyword(s):  
Cross Correlation ◽  
Minute Ventilation ◽  
Periodic Breathing ◽  
Respiratory Pattern ◽  
Volume Control ◽  
Cycle Duration ◽  
Rapid Eye Movement Sleep ◽  
The Mean ◽  
End Tidal ◽  
End Tidal Co2

We examined the control of respiratory pattern during non-rapid-eye-movement sleep-related periodic breathing (PB) in adults, with and without hypoxia. We analyzed 186 cycles of PB from 18 epochs occurring in eight subjects; the mean (+/- SD) cycle duration was 30.8 +/- 8.4 s. Significant oscillations occurred in inspired tidal volume (VT), inspiratory duration (TI), mean inspired flow, inspired minute ventilation, and expiratory duration (TE) (P less than 0.005). For each epoch of PB, moving cross-correlation (MCC) functions were employed to describe the time-dependent intervariable relationships between 1) TI vs. TE, 2) VT vs. TE, and 3) VT vs. breath duration (TT) as synchronization, a strong and consistent intervariable correlation; relative coordination (RC), a weaker interaction characterized by an unstable MCC function oscillating at a subharmonic of the PB frequency; or as independence, with no statistical evidence of interaction. Fourteen epochs showed RC between TI and TE, 11 and 12 of which also showed RC between VT and TE, and VT and TT, respectively. In 4 epochs negative synchronization was exhibited by all three variable pairs. In no case were the oscillations between any pair of variables independent. The modes of coupling between variables were not correlated to O2 saturation, end-tidal CO2 levels, or inspired O2 level. We conclude that during sleep-related PB a nonrandom but weak coupling usually exists between TI and TE, VT and TE, and VT and TT.(ABSTRACT TRUNCATED AT 250 WORDS)

State influences on ventral medullary surface and physiological responses to sodium cyanide challenges

2000 ◽  
Vol 89 (5) ◽  
pp. 1919-1927 ◽  
Author(s):  
Paul M. Macey ◽  
Christopher A. Richard ◽  
David M. Rector ◽  
Rebecca K. Harper ◽  
Ronald M. Harper
Keyword(s):  
Eye Movement ◽  
Time Course ◽  
Control Site ◽  
Sodium Cyanide ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Peripheral Chemoreceptor ◽  
Waking And Sleep ◽  
Sleep Physiology ◽  
Ventral Medullary Surface

Intravenous sodium cyanide (NaCN) administration lowers ventral medullary surface (VMS) activity in anesthetized cats. Sleep states modify spontaneous and blood pressure-evoked VMS activity and may alter VMS responses to chemoreceptor input. We studied VMS activation during peripheral chemoreceptor stimulation by intravenous NaCN using optical procedures in six cats instrumented for recording sleep physiology during sham saline and control site trials. Images of scattered 660-nm light were collected at 50 frames/s with an optical device after 80–100 μg total bolus intravenous NaCN delivery during waking and sleep states. Cyanide elicited an initial ventilatory decline, followed by large inspiratory efforts and an increase in respiratory rate, except in rapid eye movement sleep, in which an initial breathing increase occurred. NaCN evoked a pronounced decrease in VMS activity in all states; control sites and sham injections showed little effect. The activity decline was faster in rapid eye movement sleep, and the activity nadir occurred later in waking. Sleep states alter the time course but not the extent of decline in VMS activity.

scholarly journals The apneic threshold during non-REM sleep in dogs: sensitivity of carotid body vs. central chemoreceptors

2007 ◽  
Vol 103 (2) ◽  
pp. 578-586 ◽  
Author(s):  
C. A. Smith ◽  
B. J. Chenuel ◽  
K. S. Henderson ◽  
J. A. Dempsey
Keyword(s):  
Carotid Body ◽  
Pressure Support Ventilation ◽  
Pressure Support ◽  
Systemic Circulation ◽  
Peripheral Chemoreceptors ◽  
Support Ventilation ◽  
Stimulus Response ◽  
Central Chemoreceptors ◽  
End Tidal ◽  
Carotid Body Chemoreceptors

The relative importance of peripheral vs. central chemoreceptors in causing apnea/unstable breathing during sleep is unresolved. This has never been tested in an unanesthetized preparation with intact carotid bodies. We studied three unanesthetized dogs during normal sleep in a preparation in which intact carotid body chemoreceptors could be reversibly isolated from the systemic circulation and perfused. Apneic thresholds and the CO2 reserve (end-tidal Pco2 eupneic − end-tidal Pco2 apneic threshold) were determined using a pressure support ventilation technique. Dogs were studied when both central and peripheral chemoreceptors sensed transient hypocapnia induced by the pressure support ventilation and again with carotid body isolation such that only the central chemoreceptors sensed the hypocapnia. We observed that the CO2 reserve was ≅4.5 Torr when the carotid chemoreceptors sensed the transient hypocapnia but more than doubled (>9 Torr) when only the central chemoreceptors sensed hypocapnia. Furthermore, the expiratory time prolongations observed when only central chemoreceptors were exposed to hypocapnia differed from those obtained when both the central and peripheral chemoreceptors sensed the hypocapnia in that they 1) were substantially shorter for a given reduction in end-tidal Pco2, 2) showed no stimulus: response relationship with increasing hypocapnia, and 3) often occurred at a time (>45 s) beyond the latency expected for the central chemoreceptors. These findings agree with those previously obtained using an identical pressure support ventilation protocol in carotid body-denervated sleeping dogs (Nakayama H, Smith CA, Rodman JR, Skatrud JB, Dempsey JA. J Appl Physiol 94: 155–164, 2003). We conclude that hypocapnia sensed at the carotid body chemoreceptor is required for the initiation of apnea following a transient ventilatory overshoot in non-rapid eye movement sleep.

scholarly journals Ventilatory responses to specific CNS hypoxia in sleeping dogs

2000 ◽  
Vol 88 (5) ◽  
pp. 1840-1852 ◽  
Author(s):  
Aidan K. Curran ◽  
Joshua R. Rodman ◽  
Peter R. Eastwood ◽  
Kathleen S. Henderson ◽  
Jerome A. Dempsey ◽  
...  
Keyword(s):  
Eye Movement ◽  
Carotid Body ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Whole Body ◽  
Hypoxic Exposure ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Cardiorespiratory Control ◽  
Ventilatory Responses

Our study was concerned with the effect of brain hypoxia on cardiorespiratory control in the sleeping dog. Eleven unanesthetized dogs were studied; seven were prepared for vascular isolation and extracorporeal perfusion of the carotid body to assess the effects of systemic [and, therefore, central nervous system (CNS)] hypoxia (arterial [Formula: see text] = 52, 45, and 38 Torr) in the presence of a normocapnic, normoxic, and normohydric carotid body during non-rapid eye movement sleep. A lack of ventilatory response to systemic boluses of sodium cyanide during carotid body perfusion demonstrated isolation of the perfused carotid body and lack of other significant peripheral chemosensitivity. Four additional dogs were carotid body denervated and exposed to whole body hypoxia for comparison. In the sleeping dog with an intact and perfused carotid body exposed to specific CNS hypoxia, we found the following. 1) CNS hypoxia for 5–25 min resulted in modest but significant hyperventilation and hypocapnia (minute ventilation increased 29 ± 7% at arterial [Formula: see text] = 38 Torr); carotid body-denervated dogs showed no ventilatory response to hypoxia. 2) The hyperventilation was caused by increased breathing frequency. 3) The hyperventilatory response developed rapidly (<30 s). 4) Most dogs maintained hyperventilation for up to 25 min of hypoxic exposure. 5) There were no significant changes in blood pressure or heart rate. We conclude that specific CNS hypoxia, in the presence of an intact carotid body maintained normoxic and normocapnic, does not depress and usually stimulates breathing during non-rapid eye movement sleep. The rapidity of the response suggests a chemoreflex meditated by hypoxia-sensitive respiratory-related neurons in the CNS.

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