Prematurity alters hypoxic and hypercapnic ventilatory responses in developing lambs

Davey, Mary‐Ann; Moss, Timothy; McCrabb, G. J.; Harding, Richard

doi:10.1016/0034-5687(96)00038-2

Cited by 41 publications

(34 citation statements)

References 22 publications

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“…These data suggest that chronic hypercapnia has a different effect on the ventilatory response to hypercapnia when initiated before birth compared to postnatal hypercapnia, but even the effect of postnatal hypercapnia depends a great deal on the age at which the animal is exposed to hypercapnia. It is likely that the early development of the hypercapnic ventilatory response can also be affected by other environmental factors, such as oxidative stress Mulkey et al, 2003), hypoxia (McGregor et al, 1998;Simard et al, 2003), and low birth weight or pre-maturity (Davey et al, 1996).…”

Section: Modification Of the Development Of Central Chemosensitivitymentioning

confidence: 99%

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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The ventilatory response to CO 2 changes as a function of neonatal development. In rats, a ventilatory response to CO 2 is present in the first 5 days of life, but this ventilatory response to CO 2 wanes and reaches its lowest point around postnatal day 8. Subsequently, the ventilatory response to CO 2 rises towards adult levels. Similar patterns in the ventilatory response to CO 2 are seen in some other species, although some animals do not exhibit all of these phases. Different developmental patterns of the ventilatory response to CO 2 may be related to the state of development of the animal at birth. The triphasic pattern of responsiveness (early decline, a nadir, and subsequent achievement of adult levels of responsiveness) may arise from the development of several processes, including central neural mechanisms, gas exchange, the neuromuscular junction, respiratory muscles and respiratory mechanics. We only discuss central neural mechanisms here, including altered CO 2 sensitivity of neurons among the various sites of central CO 2 chemosensitivity, changes in astrocytic function during development, the maturation of electrical and chemical synaptic mechanisms (both inhibitory and excitatory mechanisms) or changes in the integration of chemosensory information originating from peripheral and multiple central CO 2 chemosensory sites. Among these central processes, the maturation of synaptic mechanisms seems most important and the relative maturation of synaptic processes may also determine how plastic the response to CO 2 is at any particular age.

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Section: Modification Of the Development Of Central Chemosensitivitymentioning

confidence: 99%

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Putnam

Conrad

Gdovin

et al. 2005

Respiratory Physiology & Neurobiology

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“…However, as FBM are restricted to levels of fetal activity, they are discontinuous, occurring <50% of the time. Further, although most FBM generate transpulmonary pressures of <20 cm H 2 O, fetuses commonly can make large inspiratory efforts (>30 cm H 2 O) [9,10], demonstrating that they are capable of generating transpulmonary pressures needed to aerate the lungs after birth [7]. The mechanisms controlling the switch to continuous breathing after birth are currently unknown.…”

Section: Pulmonary Transitionmentioning

confidence: 99%

“…Hypoxia is known to inhibit breathing movements in the fetus and the hypoxic sensitivity is relatively low shortly after birth [10]. After birth, hypoxia increasingly stimulates respiratory drive in the newborn due a temporal change in O 2 sensitivity, which increases days/weeks after birth [10].…”

Section: Pulmonary Transitionmentioning

confidence: 99%

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Measuring Physiological Changes during the Transition to Life after Birth

Vonderen¹,

et al. 2014

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The transition to life after birth is characterized by major physiological changes in respiratory and hemodynamic function, which are predominantly initiated by breathing at birth and clamping of the umbilical cord. Lung aeration leads to the establishment of functional residual capacity, allowing pulmonary gas exchange to commence. This triggers a significant decrease in pulmonary vascular resistance, consequently increasing pulmonary blood flow and cardiac venous return. Clamping the umbilical cord also contributes to these hemodynamic changes by altering the cardiac preload and increasing peripheral systemic vascular resistance. The resulting changes in systemic and pulmonary circulation influence blood flow through both the oval foramen and ductus arteriosus. This eventually leads to closure of these structures and the separation of the pulmonary and systemic circulations. Most of our knowledge on human neonatal transition is based on human (fetal) data from the 1970s and extrapolation from animal studies. However, there is renewed interest in performing measurements directly at birth. By using less cumbersome techniques (and probably more accurate), our previous understanding of the physiological transition at birth is challenged, as well as the causes and consequences for when this transition fails to progress. This review will provide an overview of physiological measurements of the respiratory and hemodynamic transition at birth. Also, it will give a perspective on some of the upcoming technological advances in physiological measurements of neonatal transition in infants who are unable to make the transition without support.

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“…Therefore, we thought that the process of labor and spontaneous delivery might prepare the lamb to breathe spontaneously. To mimic the clinical situation we gave antenatal betamethasone and an inhibitor of progesterone synthesis to induce preterm labor (16, 17). The ewes delivered without incident, and the preterm lambs had normal cord pH values and began breathing spontaneously.…”

Section: Discussionmentioning

confidence: 99%

Decreased Indicators of Lung Injury with Continuous Positive Expiratory Pressure in Preterm Lambs

Jobe

2002

Pediatric Research

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Continuous positive airway pressure (CPAP) is being used clinically to avoid mechanical ventilation of preterm infants as a strategy to minimize lung injury. There is little experimental information about how CPAP might minimize lung injury after preterm birth. We induced preterm labor in antenatal glucocorticoid-treated sheep carrying twins at 133 d gestation with an inhibitor of progesterone synthesis. The lambs delivered spontaneously approximately 2 d later and were randomized to three groups: no ventilation (n ϭ 4), conventional mechanical ventilation to a target PCO 2 of 40 mm Hg (n ϭ 5), or CPAP using a bubble CPAP device set to deliver 5 cm H 2 O pressure (n ϭ 6). The CPAP lambs breathed without distress and maintained PCO 2 values of approximately 60 mm Hg. At 2 h of age, the lungs of the CPAP lambs held 74 Ϯ 4 mL/kg air at 40 cm H 2 O pressure, which was more than the 60 Ϯ 3 mL/kg for the ventilated lambs (p Ͻ 0.05). Lymphocyte and monocyte numbers in alveolar washes were equivalent in the unventilated, ventilated, and CPAP lambs. However, no neutrophils were found in the unventilated lambs, and the ventilated lambs had 6.6 times more neutrophils in alveolar washes than did the CPAP lambs (p Ͻ 0.05). The cells in alveolar wash from CPAP lambs contained less hydrogen peroxide than did the cells from ventilated lambs The outcomes for preterm infants with RDS have improved during the last 30 y by innovations in neonatal care that include mechanical ventilation for infants, antenatal glucocorticoids, and surfactant treatments (1-3). Before these therapies were commonly available, Gregory et al. (4) described the use of a simple device to provide CPAP as a way to maintain lung gas volumes in preterm infants with RDS. The use of CPAP as a primary therapy for RDS has become less frequent in many centers because of mechanical ventilators, although it is used to facilitate extubation and to treat apnea of prematurity (5). The major pulmonary morbidity resulting from the treatment of RDS is BPD, which is frequent in infants with birth weights less than 1 kg (6). The frequency of BPD varies among neonatal units, and its occurrence has been associated by multivariant analysis with intubation and ventilation on the first day of life (7,8). In several epidemiologic studies, avoidance of mechanical ventilation and the increased use of CPAP have been associated with a decrease in BPD (9, 10). Therefore, there is a renewed interest in the use of CPAP to facilitate the initiation of spontaneous breathing and to decrease the need for mechanical ventilation of preterm infants.BPD develops in very preterm infants because lung injury is superimposed on an immature lung in the saccular stage of development (11,12). The initial inflammation and subsequent repair processes interfere with normal lung development and result in a variable pattern of alveolar simplification, fibrosis, and chronic inflammation (13,14). We found that ventilation of preterm lambs from birth initiates an inflammatory response characterized by recruitm...

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Prematurity alters hypoxic and hypercapnic ventilatory responses in developing lambs

Cited by 41 publications

References 22 publications

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Measuring Physiological Changes during the Transition to Life after Birth

Decreased Indicators of Lung Injury with Continuous Positive Expiratory Pressure in Preterm Lambs

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