Effect of Ventilatory Drive on Carbon Dioxide Sensitivity below Eupnea during Sleep

Nakayama, Hideaki; Smith, Curtis A.; Rodman, J. R.; Skatrud, James B.; Dempsey, Jerome A.

doi:10.1164/rccm.2110041

Cited by 181 publications

(124 citation statements)

References 50 publications

(71 reference statements)

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“…354 Diuresis with a reduction in cardiac filling pressure also has been shown to reduce the severity of CSA, 340 but in some patients, the resulting metabolic alkalosis may promote CSA by narrowing the difference between ambient PaCO 2 and the PaCO 2 threshold for apnea. 355,356 ␤-Adrenergic blockade, which counters excess sympathetic activation and may modulate ventilatory responses in heart failure, 18 has been reported to decrease AHI in patients with CSA. 357 However, the increasing use of such antagonists in heart failure appears not to have altered the prevalence of CSA in this condition.…”

Section: Treatment Options In Csamentioning

confidence: 99%

Sleep Apnea and Cardiovascular Disease

et al. 2008

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Section: Treatment Options In Csamentioning

confidence: 99%

Sleep Apnea and Cardiovascular Disease

et al. 2008

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“…The cause of the smaller ⌬PET CO 2 is not just due to nonspecific hypoxic stimulation of the peripheral chemoreceptor because isolated stimulation of the peripheral chemoreceptor with almitrine was not sufficient to enhance the susceptibility to posthyperventilation apnea as has been reported with hypoxia (38). The effect of hypoxia may be related to less central ventilatory drive (40) as result of medullary hypocapnia due to hypoxia-induced hyperventilation and increased cerebral blood flow.…”

Section: Discussionmentioning

confidence: 89%

“…However, carotid body denervation profoundly alters central chemoreception as indicated by the substantial CO 2 retention after denervation. Our laboratory has previously demonstrated the complex effect of hypoxia in the development of posthyperventilation apnea by showing that hypoxia is unique, compared with pure carotid body stimulants such as almitrine, in its failure to reduce the apneic threshold PCO 2 as much as the eupneic PCO 2 (38,52). As a result, the difference between the eupneic PCO 2 and the apneic threshold PCO 2 is narrowed, causing a greater susceptibility to apnea.…”

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

Xie¹,

Skatrud²,

Puleo³

et al. 2006

Journal of Applied Physiology

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Xie, Ailiang, James B. Skatrud, Dominic S. Puleo, and Jerome A. Dempsey. Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep. J Appl Physiol 100: 171-177, 2006. First published September 22, 2005 doi:10.1152/japplphysiol.00440.2005.-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 PO 2. 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 O 2 saturation ϭ 78 -80%), and hyperoxia (inspired O2 fraction ϭ 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 Ϯ 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 Ϯ 0.8 s; P Ͻ 0.05), whereas hyperoxia prolonged it (71.5 Ϯ 13.8 s; P Ͻ 0.01). The apneic threshold end-tidal PCO 2 (PETCO 2 ) was defined as the PETCO 2 at the onset of apnea. During hypoxia, the apneic threshold PET CO 2 was higher (38.9 Ϯ 1.7 Torr; P Ͻ 0.01) compared with normoxia (35.8 Ϯ 1.1; Torr); during hyperoxia, it was lower (33.0 Ϯ 0.8 Torr; P Ͻ 0.05). Furthermore, the difference between the eupneic PET CO 2 and apneic threshold PET CO 2 was smaller during hypoxia (3.0 Ϯ 1.0 Torr P Ͻ 001) and greater during hyperoxia (10.6 Ϯ 0.8 Torr; P Ͻ 0.05) compared with normoxia (8.0 Ϯ 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO 2 below the eupneic PETCO 2 was increased by hypoxia (3.44 Ϯ 0.63 l ⅐ min Ϫ1 ⅐ Torr Ϫ1 ; P Ͻ 0.05) and decreased by hyperoxia (0.63 Ϯ 0.04 l ⅐ min Ϫ1 ⅐ Torr Ϫ1 ; P Ͻ 0.05) compared with normoxia (0.79 Ϯ 0.05 l ⅐ min Ϫ1 ⅐ Torr Ϫ1 ). 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. apnea threshold THE RELATIVE CONTRIBUTION of peripheral vs. central chemoreception in initiating the posthyperventilation apneas remains an unresolved question. The importance of peripheral chemoreception in mediating the rapid ventilatory response to hypocapnia has been supported using animal models. Carotid body denervation either eliminated or prolonged the time course for the development of apnea after the administration of augmented breaths (6, 39). However, carotid body denervation profoundly alters central chemoreception as indicated by the substantial CO 2 retention after denervation. Our laboratory has previously demonstrated the complex effect of hypoxia in t...

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“…Recently, a good deal of attention has been focused on the role of proximity of the eupneic point to the CO 2 apneic threshold (10,35,45). The concept of a CO 2 reserve, defined as the difference between the end-tidal CO 2 at eupnea and the endtidal CO 2 at the apneic threshold, has developed (46), and its magnitude has been used as an explanation for the occurrence of apnea and PB.…”

Section: Discussionmentioning

confidence: 99%

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb

Wilkinson¹,

Sia²,

Skuza³

et al. 2005

Journal of Applied Physiology

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. Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb. J Appl Physiol 98: 437-446, 2005. First published October 8, 2004 doi:10.1152/japplphysiol.00532.2004We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in seven lambs following posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or loop gain (LG) of the respiratory control system of the lamb is directly proportional to the difference between alveolar PO2 and inspired PO2. This analysis indicates that during PB, when by necessity LG is Ͼ1, replacement of the inspired gas with one of reduced PO2 lowers LG; if we made inspired PO2 approximate alveolar PO2, we predict that LG would be approximately zero and breathing would promptly stabilize. In six lambs, we switched the inspired gas from an inspiratory oxygen fraction of 0.4 to one of 0.12 during an epoch of PB; PB was immediately suppressed, supporting the view that the peripheral chemoreceptors play a pivotal role in the genesis and control of unstable breathing in the lamb. In the six lambs in which we administered hypercapnic gas during PB, breathing instability was also suppressed, but only after a considerable time lag, indicating the CO2 effect is likely to have been mediated through the central chemoreceptors. When we simulated both interventions in a published model of the adult respiratory controller, PB was immediately suppressed by CO2 inhalation and exacerbated by inhalation of hypoxic gas. These fundamentally different responses in lambs and adult humans demonstrate that PB has differing underlying mechanisms in the two species.Cheyne-Stokes respiration; hypoxia; hypercapnia; sleep apnea syndromes; control of breathing; periodic breathing PERIODIC BREATHING (PB), or Cheyne-Stokes respiration, appears under a wide range of physiological and clinical conditions. It is particularly prevalent during sleep, occurring at sea level in apparently normal-term and preterm infants (22,43), at high altitude in normal adults (27), and after hypoxic exposure in experimental animals (11,21). It also occurs in patients with congestive heart failure (36), with idiopathic central sleep apnea (52), with bilateral brain stem lesions (40), and in periodic obstructive sleep apnea (41). A form of PB can also be found in hibernating animals (7,34).Although it is often assumed that the underlying mechanisms causing PB in infants and adults are similar, in each case involving instability of the chemical control system that regulates breathing, there are some marked differences in the pattern of PB and its responses to changes in inspired gas that remain largely unexplained. For example, in preterm infants, the waxing and waning pattern of PB that is characteristic of the adult is replaced by a more or less abrupt on-off pattern that shows little change in tidal volume during the breathing phase (42); this pattern resembles that seen in hibernating animals (34). Furthermore, although the re...

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Effect of Ventilatory Drive on Carbon Dioxide Sensitivity below Eupnea during Sleep

Cited by 181 publications

References 50 publications

Sleep Apnea and Cardiovascular Disease

Sleep Apnea and Cardiovascular Disease

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

Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb

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