Increased peripheral chemoreceptor activity may be critical in destabilizing breathing in neonates

Al-Matary, Abdulrahman; Kutbi, Ibrahim; Qurashi, Mansour; Khalil, Mohammed; Alvaro, Ruben; Kwiatkowski, Kim; Cates, Don; Rigatto, Henrique

doi:10.1053/j.semperi.2004.08.003

Cited by 88 publications

(48 citation statements)

References 22 publications

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“…If a correlation exists between PCD and epoch length, the use of long epochs could lead to a selection bias favoring larger PCD values and, as we argue later, a different pattern of maturation. Such a correlation might be expected on theoretical grounds, inasmuch as our calculations using a math model of the infant control system (3,4) assuming mild hypoxia associated with intrapulmonary shunting in the early postnatal period (14) show that, if we assume changes in PCD are mediated through changes in circulatory delay (Fig. 5), then state-related changes in cardiac output would be expected to strongly mediate such changes.…”

Section: Discussionmentioning

confidence: 97%

“…Second, the temporally matched fall in PCD with PNA in the preterm and term infants suggests that the respiratory control system undergoes an adaptation to air breathing starting soon after birth, and that this adaptation is completed by 4 mo postnatally, regardless of whether birth is preterm or term. Third, since a number of studies suggest a dominant role for the peripheral chemoreceptors in the genesis of respiratory instability (3,4,6,14,20,21), the fall in PCD with PNA specifically points to a shortening of the time delays in the peripheral chemoreflex loop as causative. Interestingly, recent evidence suggests that delays in the response to a hypercapnic stimulus are significantly reduced in human infants over the first weeks of life while the peripheral O 2 chemoreflex shows little change (9).…”

Section: Pb Cycle Duration In Infantsmentioning

confidence: 99%

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Postnatal Development of Periodic Breathing Cycle Duration in Term and Preterm Infants

Wilkinson

Skuza

Rennie³

et al. 2007

Pediatr Res

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Previous studies of the maturation of periodic breathing cycle duration (PCD) with postnatal age in infants have yielded conflicting results. PCD is reported to fall in term infants over the first 6 mo postnatally, whereas in preterm infants PCD is reported either not to change or to fall. Contrary to measured values, use of a theoretical respiratory control model predicts PCD should increase with postnatal age. We re-examined this issue in a longitudinal study of 17 term and 22 preterm infants. PCD decreased exponentially from birth in both groups, reaching a plateau between 4 and 6 mo of age. In preterm infants, PCD fell from a mean of 18.3 s to 9.8 s [95% confidence interval (CI) is Ϯ 3.2 s]. In term infants, PCD fell from 15.4 s to 10.1 s (95% CI is Ϯ 3.1 s). The higher PCD at birth in preterm infants, and the similar PCD value at 6 mo in the two groups, suggest a more rapid maturation of PCD in preterm infants. This study confirms that PCD declines after birth. The disagreement between our data and theoretical predictions of PCD may point to important differences between the respiratory controller of the infant and adult. E xperimental evidence is accumulating that PB in the infant, as in the adult, is caused by instability in the respiratory control system, possibly mediated by increased hypoxic stimulation of the peripheral chemoreflex feedback loop during the early postnatal period (1,2). Furthermore, math modeling studies of respiratory control based on a downscaling of adult cardiorespiratory time constants to the infant (3,4) support such a conclusion. Of interest, the theoretical model of Khoo et al. (3) predicts that the PCD should increase progressively with age from approximately 18 s at birth to an adult value in excess of 30 s.Surprisingly, most infant data contradict this model prediction, with three longitudinal studies in term infants (5-7) and one small study in preterm infants (1) reporting that PCD decreases significantly from birth to 6 mo postnatally. However, another cross-sectional study of selected long epochs of PB in a larger group of preterm infants studied just before discharge from the nursery reported that PCD showed no trend or a weakly increasing trend over the first 3 mo postnatally (8); while the results of this study could be interpreted as conforming with the predictions of the Khoo model scaled to the infant, we have argued previously that the study design may have biased the outcome (1).To resolve the issue as to whether PCD decreases or increases with postnatal age, further longitudinal studies were warranted in a larger population of term and preterm infants. Based on our earlier studies, and consistent with recent findings that the ventilatory response to CO 2 becomes brisker with age (9), we hypothesized that the reduction in PCD commencing at birth and completed by 6 mo postnatally in both term and preterm infants represents a similar adaptation to air breathing and is mediated principally by changes in the response time of the peripheral chemoreceptors. ...

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Section: Discussionmentioning

confidence: 97%

Section: Pb Cycle Duration In Infantsmentioning

confidence: 99%

Postnatal Development of Periodic Breathing Cycle Duration in Term and Preterm Infants

Wilkinson

Skuza

Rennie³

et al. 2007

Pediatr Res

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“…Although we measured SpO 2 only, the latter parameter is thought to accurately reflect the simultaneous PaO 2 (26); in our work, SpO 2 was negatively correlated with FRC. Recent studies (27,28) have reported that a low PaO 2 magnifies the peripheral chemoreceptors' contribution to breathing and induces major ventilatory changes. As a result, respiratory instability and increased apnea frequency may be observed.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Functional Residual Capacity and Oxygen Desaturation During Short Central Apneic Events During Sleep in “Late Preterm” Infants

et al. 2008

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Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O 2 -desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O 2 -desaturation during short central apneic events (Ͼ3 s) in "late-preterm" infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 Ϯ 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O 2 -desaturation (drop in SpO 2 Ͼ5% from the baseline, lowest SpO 2 during apnea: 91.4 Ϯ 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O 2 -desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.

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“…In rat pups, the incidence of apneas correlates positively with the magnitude of the HVR (Julien et al, 2008). In preterm infants, an augmented (rather than reduced) O 2 chemoreflex, as indicated by the rapid change in breathing that occurs during exposure to moderate hypoxia or hyperoxia, exacerbates periodic breathing and promotes apneas (Al-Matary et al, 2004;Gauda et al, 2004). Conversely, a reduced ventilatory response to CO 2 contributes to respiratory disorders in the newborn, such as apnea of prematurity (KatzSalamon, 2004;Gaultier and Gallego, 2005), and is a risk factor for SIDS (Gauda et al, 2004;.…”

Section: Mechanisms By Which Gs Promotes Respiratory Instability and mentioning

confidence: 99%

Gestational Stress Promotes Pathological Apneas and Sex-Specific Disruption of Respiratory Control Development in Newborn Rat

et al. 2013

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Recurrent apneas are important causes of hospitalization and morbidity in newborns. Gestational stress (GS) compromises fetal brain development. Maternal stress and anxiety during gestation are linked to respiratory disorders in newborns; however, the mechanisms remain unknown. Here, we tested the hypothesis that repeated activation of the neuroendocrine response to stress during gestation is sufficient to disrupt the development of respiratory control and augment the occurrence of apneas in newborn rats. Pregnant dams were displaced and exposed to predator odor from days 9 to 19 of gestation. Control dams were undisturbed. Experiments were performed on male and female rats aged between 0 and 4 d old. Apnea frequency decreased with age but was consistently higher in stressed pups than controls. At day 4, GS augmented the proportion of apneas with O 2 desaturations by 12%. During acute hypoxia (12% O 2 ), the reflexive increase in breathing augmented with age; however, this response was lower in stressed pups. Instability of respiratory rhythm recorded from medullary preparations decreased with age but was higher in stressed pups than controls. GS reduced medullary serotonin (5-HT) levels in newborn pups by 32%. Bath application of 5-HT and injection of 8-OH-DPAT [(Ϯ)-8-hydroxy-2-di-(n-propylamino) tetralin hydrobromide; 5-HT 1A agonist; in vivo] reduced respiratory instability and apneas; these effects were greater in stressed pups than controls. Sex-specific effects were observed. We conclude that activation of the stress response during gestation is sufficient to disrupt respiratory control development and promote pathological apneas in newborn rats. A deficit in medullary 5-HT contributes to these effects.

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Increased peripheral chemoreceptor activity may be critical in destabilizing breathing in neonates

Cited by 88 publications

References 22 publications

Postnatal Development of Periodic Breathing Cycle Duration in Term and Preterm Infants

Postnatal Development of Periodic Breathing Cycle Duration in Term and Preterm Infants

Relationship Between Functional Residual Capacity and Oxygen Desaturation During Short Central Apneic Events During Sleep in “Late Preterm” Infants

Gestational Stress Promotes Pathological Apneas and Sex-Specific Disruption of Respiratory Control Development in Newborn Rat

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