Postnatal changes in ventilation during normoxia and acute hypoxia in the rat: implication for a sensitive period

Liu, Qiuli; Lowry, T. F.; Wong‐Riley, Margaret T.T.

doi:10.1113/jphysiol.2006.121970

Cited by 73 publications

(134 citation statements)

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“…Dynamic compliance was estimated from data obtained during a single-frequency forced oscillation maneuver, using a mathematical model-fitting technique according to the specifications of Scireq Inc. (Montreal, PQ). To determine ventilator settings, we started with the normal breathing frequency of a 8-d-old rat [ϳ160/min (15)] and adjusted V T and positive end expiratory pressure (PEEP) to achieve normal blood gases. The V T and PEEP values for this frequency were ϳ12.5 mL.kg Ϫ1 and 2 cm H 2 O, respectively.…”

Section: Animalsmentioning

confidence: 99%

Inflammatory Response to Oxygen and Endotoxin in Newborn Rat Lung Ventilated With Low Tidal Volume

et al. 2010

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Herein, we determined the contribution of mechanical ventilation, hyperoxia and inflammation, individually or combined, to the cytokine/chemokine response of the neonatal lung. Eight-dayold rats were ventilated for 8 h with low (ϳ3.5 mL/kg), moderate (ϳ12.5 mL/kg), or high (ϳ25 mL/kg) tidal volumes (V T ) and the cytokine/chemokine response was measured. Next, we tested whether low-V T ventilation with 50% oxygen or a preexisting inflammation induced by lipopolysaccharide (LPS) would modify this response. High-, moderate-, and low-V T ventilation significantly elevated CXCL-2 and IL-6 mRNA levels. Low-V T ventilation with 50% oxygen significantly increased IL-6 and CXCL-2 expression versus low-V T ventilation alone. LPS pretreatment combined with low-V T ventilation with 50% oxygen amplified IL-6 mRNA expression when compared with low V T alone or low V T ϩ 50% O 2 treatment. In contrast, low V T up-regulated CXCL-2 levels were reduced to nonventilated levels when LPS-treated newborn rats were ventilated with 50% oxygen. Thus, low-V T ventilation triggers the expression of acute phase cytokines and CXC chemokines in newborn rat lung, which is amplified by oxygen but not by a preexisting inflammation. Depending on the individual cytokine or chemokine, the combination of both oxygen and inflammation intensifies or abrogates the low V T -induced inflammatory response. (Pediatr Res 68: 63-69, 2010) B ronchopulmonary dysplasia (BPD) remains the most important cause of respiratory morbidity in very low birth weight infants. Mechanical ventilation (MV), intra-uterine infections and oxidative stress up-regulate proinflammatory cytokines/chemokines including IL-1␤, IL-6, and IL-8 (1). Elevated concentrations of these cytokines/chemokines in amniotic fluid and bronchoalveolar lavage fluid (BALF) have been associated with BPD (2,3). The contribution of each risk factor, alone or combined, to the inflammatory response remains to be determined.Ample animal studies have suggested that high frequency oscillatory ventilation (HFOV) is less injurious compared with conventional ventilation (CMV) (4,5). However, in the baboon model of BPD impaired alveolarization and capillary development occurred in spite of appropriate oxygenation and use of HFOV (4). MV with moderate and high tidal volumes increased lung cytokine/chemokine response to systemic endotoxin in rabbits (6) and newborn rats (7). Oxidant injury alone can produce the pathologic features of BPD (8). Inflammatory cells such as monocytes and neutrophils are primary contributors to the oxygen-induced lung injury (9,10). Other animal studies have investigated the contributions of oxygen exposure and MV alone or in combination. In term ventilated piglets hyperoxia caused less lung damage than hyperoxia combined with hyperventilation but more than hyperventilation alone (11). Premature baboons ventilated with the minimum necessary supplemental oxygen had significant less damage than those ventilated with 100% oxygen (12), but alveolarization and capillary developmen...

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Section: Animalsmentioning

confidence: 99%

Inflammatory Response to Oxygen and Endotoxin in Newborn Rat Lung Ventilated With Low Tidal Volume

et al. 2010

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“…We hypothesized that at and around P12 is a sensitive period in the postnatal development of the rat's respiratory control network, when a transient dominance of inhibitory over excitatory neurotransmission renders the animals less capable of overcoming exogenous respiratory stressors. Our subsequent ventilatory studies revealed striking changes in normoxic ventilation as well as hypoxic ventilatory response (HVR) at and around P13, with a peak in respiratory frequency and a transient peak both in tidal volume (VT) and minute ventilation (V E) under normoxia (32). The body temperature also peaked at P13.…”

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confidence: 99%

“…The body temperature also peaked at P13. Significantly, the lowest HVR (decreased frequency response and the lowest VT response; therefore, the lowest V E response) was also at P13 (32). Thus the end of the second postnatal week is likely to be a critical period during which the animals are less responsive to external stressors, such as hypoxia.…”

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confidence: 99%

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Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

Liu¹,

Fehring²,

Lowry³

et al. 2009

Journal of Applied Physiology

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Liu Q, Fehring C, Lowry TF, Wong-Riley MTT. Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period. J Appl Physiol 106: 1212-1222, 2009. First published December 31, 2008 doi:10.1152/japplphysiol.90949.2008.-Previously, we reported that the hypoxic ventilatory response (HVR) in rats was weakest at postnatal day (P) P13, concomitant with neurochemical changes in respiratory nuclei. A major determinant of minute ventilation (V E) is reportedly the metabolic rate [O2 consumption (V O2) and CO2 production (V CO2)]. The present study aimed at testing our hypothesis that daily metabolic rates changed in parallel with ventilation during development and that a weak HVR at P13 was attributable mainly to an inadequate metabolic rate in hypoxia. Ventilation and metabolic rates were monitored daily in P0 -P21 rats. We found that 1) ventilation and metabolic rates were not always correlated, and V E/V O2 and V E/V CO2 ratios were not constant during development; 2) metabolic rate and V E/V O2 and V E/V CO2 ratios at P0 -P1 were significantly different from the remaining first postnatal week in normoxia and hypoxia; 3) at P13, metabolic rates and V E/V O2 and V E/V CO2 ratios abruptly increased in normoxia and were compromised in acute hypoxia, unlike more stable trends during the remaining second and third postnatal weeks; and 4) the respiratory quotient (V CO2/V O2) was quite stable in normoxia and fluctuated slightly in hypoxia from P0 to P21. Thus our data revealed heretofore unsuspected metabolic adjustments at P0 -P1 and P13. At P0 -P1, ventilation and metabolic rates were uncorrelated, whereas at P13, they were closely correlated under normoxia and hypoxia. The findings further strengthened the existence of a critical period of respiratory development around P13, when multiple physiological and neurochemical adjustments occur simultaneously. carbon dioxide production; critical period; oxygen consumption; respiratory quotient; ventilation PREVIOUSLY, WE CONDUCTED DETAILED, day-to-day studies of various brain stem respiratory nuclei of the rat and found that neurotransmitters and receptors underwent distinct developmental changes. Significantly, at or around postnatal day (P) 12, the expression of excitatory neurotransmitter glutamate and its N-methyl-D-aspartate receptors dropped precipitously, whereas the expression of inhibitory neurotransmitter ␥-aminobutyric acid (GABA), GABA B receptors, and glycine receptors rose sharply (27,30, 61). Concomitantly, there was a sudden fall in cytochrome oxidase activity (27,28, 61), a sensitive indicator of metabolic capacity and neuronal activity (60). We hypothesized that at and around P12 is a sensitive period in the postnatal development of the rat's respiratory control network, when a transient dominance of inhibitory over excitatory neurotransmission renders the animals less capable of overcoming exogenous respiratory stressors. Our subsequent ventilatory studies revealed striking changes in normoxic ventilation ...

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“…Why animals did not hyperventilate at P12 is unknown, but it may reflect either the high tidal volume observed in control animals (probably a result of the highly variable breathing pattern and the switch from neonatal to adult breathing in this age group), which stabilised during CO 2 exposure, or a window of development where these animals are more vulnerable to hypoxia. Such a window of vulnerability has been reported in P12 rats with an absence of increasing V E /V O2 , due to a decrease in tidal volume and a comparatively weak metabolic response to hypoxia; a response that was different from that in the rest of the first 3 postnatal weeks (Liu et al, 2006). In addition, a reduction in excitatory and an increase in inhibitory neurotransmitters (Wong-Riley and Liu, 2005) as well as a significant decline in tryptophan hydroxylase and serotonin transporter immunoreactivity (Liu and Wong-Riley, 2010b;Liu and Wong-Riley, 2010a) further suggests that normal development can contribute to a narrow window of vulnerability in rats at this age (P12), though lack of proper controls limits the interpretation of these developmental studies.…”

Section: The Journal Of Experimental Biology 215 (24)mentioning

confidence: 98%

The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart

Simpson

Fong

Cummings

et al. 2012

Journal of Experimental Biology

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SUMMARYAt birth, the newborn fat-tailed dunnart relies on cutaneous gas exchange to meet metabolic demands, with continuous lung ventilation emerging several days later. We hypothesised that the delayed expression of lung ventilation (V E ) in these animals is in part due to a low responsiveness of the respiratory control system to blood gas perturbations. To address this hypothesis, we assessed the ventilatory and metabolic response to hypoxia (10% O 2 ) and hypercapnia (5% CO 2 ) using closed-system respirometry from birth to 23days postpartum (P). Neonatal fat-tailed dunnarts displayed no significant hypoxic or hypercapnic ventilatory responses at any age. Regardless, significant hyperventilation through a suppression of metabolic rate (V O2 ) was observed at birth in response to hypercapnia and in response to hypoxia at all ages, except P12. Therefore, reliance on cutaneous gas exchange during early life may be partially attributed to reduced chemosensitivity or a lack of central integration of chemosensitive afferent information. This may be in part due to the relative immaturity of this species at birth, compared with other mammals.

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Postnatal changes in ventilation during normoxia and acute hypoxia in the rat: implication for a sensitive period

Cited by 73 publications

References 62 publications

Inflammatory Response to Oxygen and Endotoxin in Newborn Rat Lung Ventilated With Low Tidal Volume

Inflammatory Response to Oxygen and Endotoxin in Newborn Rat Lung Ventilated With Low Tidal Volume

Postnatal development of metabolic rate during normoxia and acute hypoxia in rats: implication for a sensitive period

The ventilatory response to hypoxia and hypercapnia is absent in the neonatal fat-tailed dunnart

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