Surfactant Increases the Uniformity of Lung Aeration at Birth in Ventilated Preterm Rabbits

Siew, Melissa Li-Lian; Pas, Arjan B. te; Wallace, Megan Jane; Kitchen, Marcus John; Islam, M.S.; Lewis, Robert A.; Fouras, Andreas; Morley, Colin J; Davis, Peter G; Yagi, Naoto; Uesugi, Kentaro; Hooper, Stuart B.

doi:10.1203/pdr.0b013e31821be094

Cited by 39 publications

(43 citation statements)

References 21 publications

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“…PC X-ray images of the lungs at FRC were analyzed to assess the uniformity of lung aeration using a phase retrieval analysis that calculates lung gas volumes from the images (27,37,38). PC X-ray images were divided into four quadrants, vertically down the spine and horizontally at the seventh rib.…”

Section: Methodsmentioning

confidence: 99%

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits

et al. 2012

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Background: Recent phase-contrast X-ray imaging studies suggest that inspiration primarily drives lung aeration and airway liquid clearance at birth, which questions the role of adrenaline-induced activation of epithelial sodium channels (eNacs). We hypothesized that pressures generated by inspiration have a greater role in airway liquid clearance than do eNacs after birth. Methods: Rabbit pups (30 d of gestation) were delivered and sedated, and 0.1 ml of saline (s) or amiloride (Am; an eNac inhibitor) was instilled into the lungs before mechanical ventilation. Two other groups (30 d of gestation) were treated similarly but were also given adrenaline (s/Ad and Am/Ad) before mechanical ventilation. results: Amiloride and adrenaline did not affect functional residual capacity (FRc) recruitment (P > 0.05). Amiloride increased the rate of FRc loss between inflations (Am: −5.2 ± 0.6 ml/kg/s), whereas adrenaline reduced the rate of FRc loss (s/Ad: −1.9 ± 0.3 ml/kg/s) as compared with saline-treated controls (s: −3.5 ± −0.6 ml/kg/s; P < 0.05). conclusion: These data indicate that inspiration is a major determinant of airway liquid clearance and FRc development during positive pressure ventilation. Although eNac inhibition and adrenaline administration had no detectable effect on FRc development, eNac may help to prevent liquid from re-entering the airways during expiration. a t birth, airway liquid clearance and lung aeration initiate cardiopulmonary changes, and together they underpin the transition to newborn life. Airway liquid clearance is accomplished by a variety of mechanisms (1-3), depending on the mode and timing of delivery. However, cell culture (4,5), animal (6-8), and human (9,10) studies imply that adrenaline-induced activation of pulmonary epithelial sodium channels (ENaCs) is the primary mechanism. This predicts that increased Na + reabsorption from the lung lumen reverses the osmotic gradient across the pulmonary epithelium, favoring liquid movement from the airways into the interstitial tissue (11-13). However, no studies have assessed the independent effects of ENaC inhibition vs. other factors such as increased transpulmonary hydrostatic pressures generated by inspiration. These transpulmonary pressures refer to the pressure difference across the pulmonary epithelium between the distal airways and the surrounding interstitial tissue.Phase-contrast (PC) X-ray imaging exploits the refractive index difference between air and water to generate high-resolution images of the aerating lung after birth. As X-rays pass through the aerated lung, they are refracted at each air-liquid interface, which generates a characteristic "speckle" pattern from which lung gas volumes can be determined (14-16). Together with plethysmography, PC X-ray imaging has demonstrated the dependence of lung aeration on inspiratory activity after birth (17,18). These data have questioned the role of Na + reabsorption and suggest that inspiration may be the primary force promoting airway liquid clearance after birth. However, because ...

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Section: Methodsmentioning

confidence: 99%

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits

et al. 2012

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“…Surfactant also plays an important role in creating and maintaining FRC at birth, by reducing the surface tension, lung recoil and the transpulmonary pressure gradient for lung liquid moving back to the alveolar space [50,51]. In addition, surfactant greatly increases the uniformity of lung aeration, which indicates that surface tension determines whether the air/liquid interface progresses down both airways at each airway branch [51].…”

Section: Pulmonary Transitionmentioning

confidence: 99%

“…In addition, surfactant greatly increases the uniformity of lung aeration, which indicates that surface tension determines whether the air/liquid interface progresses down both airways at each airway branch [51]. …”

Section: Pulmonary Transitionmentioning

confidence: 99%

Measuring Physiological Changes during the Transition to Life after Birth

Vonderen¹,

Roest

Siew

et al. 2014

Neonatology

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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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“…Siew et al [10] showed that PEEP greatly facilitates aeration of the distal airways and prevents distal airway collapse at end expiration in very preterm rabbits mechanically ventilated from birth. In a later study [11] the same group showed that PEEP and Curosurf ® had additive effects on functional residual capacity and that Curosurf markedly improved the uniformity of ventilation irrespective of whether or not PEEP was applied. These results are in agreement with our results using preterm rabbits.…”

Section: Surfactant Activitymentioning

confidence: 95%

New Generation Synthetic Surfactants

2013

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The treatment of preterm newborn rabbits with synthetic surfactants containing simple phospholipid mixtures and peptides gives similar tidal volumes to treatment with poractant alfa (Curosurf®). The addition of both surfactant protein B and C analogs to the phospholipid mixture will stabilize the alveoli, measured as lung gas volumes at end expiration, even if no positive end-expiratory pressure is applied. The effect on lung gas volumes seems to depend on the structure of the peptides as well as the phospholipid composition. It seems that synthetic surfactants containing two peptides and a more complex phospholipid composition will be able to replace natural surfactants within the near future, but more experiments need to be performed before any conclusion can be drawn about the ideal composition of this new generation of synthetic surfactants.

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Surfactant Increases the Uniformity of Lung Aeration at Birth in Ventilated Preterm Rabbits

Cited by 39 publications

References 21 publications

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits

The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits

Measuring Physiological Changes during the Transition to Life after Birth

New Generation Synthetic Surfactants

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