Effect of Increased Lung Expansion on Surfactant Protein mRNA Levels in Lambs

Lines, Andrea; Davey, Mary‐Ann; Harding, Richard; Hooper, Stuart B.

doi:10.1203/00006450-200112000-00015

Cited by 10 publications

(13 citation statements)

References 32 publications

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“…Increased lung expansion in an animal model of fetal tracheal obstruction, known to be a potent stimulus for fetal lung growth, caused simultaneous reduction in SP-A, SP-B and SP-C mRNA levels in the fetal lung already within 2 days [16]. However, increased lung expansion post-natally by CPAP for 96 h does not affect surfactant protein gene expression in the preterm lamb [17,18].…”

Section: Animal Models Of Cpapmentioning

confidence: 89%

Interaction between Surfactant and Ventilatory Support in Newborns with Primary Surfactant Deficiency

Plavka

Keszler

2003

Neonatology

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The interaction between exogenous surfactant and various modes of ventilatory support in terms of timing, quality and quantity can influence both short- and long-term outcomes of immature infants. Alterations to the pulmonary surfactant system can occur with all forms of mechanical ventilation. Experimental data suggest possible interaction between ventilatory support and exogenous surfactant even during the first breaths in the delivery room. The adverse effect on surfactant function at this time can increase the need for and duration of ventilatory support. The logical approach to ventilatory support is to be minimally aggressive with optimal recruitment of the lungs to avoid ventilator-induced lung injury. Nasal continuous positive airway pressure (CPAP) in combination with early prophylactic surfactant administration may be an effective and less damaging method capable of reducing the need of artificial ventilation, but its benefit has not been proven in extremely preterm infants less than 28 weeks’ gestation. Because of unproven efficacy of nasal CPAP in extremely premature infants, the population most at risk for adverse pulmonary and neurologic outcome, this paper focuses on the comparison of conventional and high-frequency oscillatory ventilation (HFOV) with respect to alteration of surfactant function, and short- and long-term outcomes, in both human and experimental trials. Though the two most recent large clinical trials provide reassurance with respect to the safety of first-intention high-frequency ventilation, the reduction in the risk of chronic lung disease appears to be only modest or absent. Recent laboratory investigations suggest that the key element of HFOV, namely optimization of volume, can, under some circumstances, be replicated with low tidal volume conventional ventilation and high positive end-expiratory pressure. Recent introduction of patient-triggered volume-targeted conventional ventilation into clinical practice offers the promise of a practical means of providing gentle conventional ventilation capable of minimizing ventilator-induced lung injury. Ultimately, well-designed comparative clinical trials with long-term outcomes are essential to accurately quantify risks and benefits of any new approach to mechanical ventilation. Without such data, these experimental results should not be extrapolated into clinical practice, because of the multifactorial pathophysiology of the development of chronic pulmonary disease in extremely premature infants and the risk of unanticipated adverse effects.

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Section: Animal Models Of Cpapmentioning

confidence: 89%

Interaction between Surfactant and Ventilatory Support in Newborns with Primary Surfactant Deficiency

Plavka

Keszler

2003

Neonatology

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“…Gas exchange Improved ventilation [3,27] Improved oxygenation [23,26] Transient respiratory acidosis [3,26,31,32] Lung function and compliance Improved gas volume [3,26,27] Improved compliance (ex vivo) [3,26,27] Pulmonary surfactant Increased surfactant availability (BAL) compared to unventilated control [3,27] Lung injury/inflammation Decreased lung injury [3], similar induction of inflammatory cytokine [23] Response to intrapulmonary therapy Exogenous surfactant improved oxygenation with CPAP [18] Term lamb No ventilation: Lines et al [17], Martin et al [35] MV: Todd et al [28], Martin et al [35] Lung structure None…”

Section: Large Animalmentioning

confidence: 99%

“…Equally improved oxygenation [35], increased PaCO 2 in CPAP [35], equivalent gas exchange [17] Lung function and compliance Improved functional residual capacity [17] Pulmonary surfactant No effect on surfactant mRNA expression [17] Lung injury/inflammation Equivalent airway injury [28] Response to intrapulmonary therapy None Baboon Unventilated: Thomson et al [33] MV: Thomson et al [33,34] Lung structure No/limited disruption to alveolar development [33,34] Gas exchange Gas exchange not disrupted by CPAP [33], improved oxygenation and ventilation [34] Lung function and compliance Increased compliance [33] Pulmonary surfactant None…”

Section: Gas Exchangementioning

confidence: 99%

A Systematic Review of the Influence of Continuous Positive Airway Pressure on Fetal and Newborn Animal Models: Suggestions to Improve Neonatal Respiratory Care

et al. 2020

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Introduction: Prematurely born infants regularly develop respiratory distress syndrome and require assisted ventilation. Ventilation may injure the premature lung and increase the risk of bronchopulmonary dysplasia. Continuous positive airway pressure (CPAP), a form of noninvasive ventilation, is commonly used in modern neonatology. Limited clinical data are available on the acute and long-term effect of neonatal exposure to CPAP on the lung. Given the restricted clinical data, newborn animal models have been used to study the influence of CPAP on lung structure and function. The findings of animal studies can guide neonatal care and improve the use of CPAP. Methods: A systematic review of electronic databases (Medline, Embase, and Cinahl) was performed using the medical subject heading terms, “CPAP” or “continuous positive airway pressure” and “animals” and “newborn.” Abstracts were screened for inclusion using predetermined eligibility criteria. Results: In total, 235 abstracts were identified and screened for inclusion. Of these, 21 papers were included. Large (N = 18) and small (N = 3) animal models investigated the effects of CPAP. Pulmonary outcomes included gas exchange, lung structure and function, surfactant metabolism, lung inflammation and injury, and the effect of intrapulmonary therapy. Compared to mechanical ventilation, CPAP improves lung function, evokes less lung injury, and does not disrupt alveolar development. Surfactant administration combined with CPAP further improves respiratory outcomes. Of concern are findings that CPAP may increase airway reactivity. Discussion/Conclusion: CPAP offers numerous advantages over mechanical ventilation for the immature lung. The combination of CPAP and exogenous surfactant administration offers further pulmonary benefit.

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“…Similarly, the application of continuous positive airway pressure (CPAP) to newborn ferret pups for 2 wk also increases lung weights (32). On the other hand, we have previously found no effect of 12 h of CPAP on postnatal lung growth or surfactant protein mRNA levels in newborn lambs (19). Thus the question of whether lung expansion regulates postnatal lung growth and AEC differentiation after birth is not resolved.…”

mentioning

confidence: 98%

Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs

Flecknoe

Crossley²,

Zuccala³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Although increased lung expansion markedly alters lung growth and epithelial cell differentiation during fetal life, the effect of increasing lung expansion after birth is unknown. We hypothesized that increased basal lung expansion, caused by ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and decrease surfactant protein mRNA levels. Two groups of lambs were sedated and ventilated with either 0 cmH(2)O PEEP (controls, n = 5) or 10 cmH(2)O PEEP (n = 5) for 48 h beginning at 15 +/- 1 days after normal term birth. A further group of nonventilated 2-wk-old lambs was used for comparison. We determined wet and dry lung weights, DNA and protein content, a labeling index for proliferating cells, surfactant protein mRNA expression, and proportions of AECs using electron microscopy. Although ventilating lambs for 48 h with 10 cmH(2)O PEEP did not affect total lung DNA or protein, it significantly increased the proportion of proliferating cells in the lung when compared with nonventilated 2-wk-old controls and lambs ventilated with 0 cmH(2)O PEEP (control: 2.6 +/- 0.5%; 0 PEEP: 1.9 +/- 0.3%; 10 PEEP: 3.5 +/- 0.3%). In contrast, no differences were observed in AEC proportions or surfactant protein mRNA levels between either of the ventilated groups. This study demonstrates that increases in end-expiratory lung volumes, induced by the application of PEEP, lead to increased lung growth in mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.

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Effect of Increased Lung Expansion on Surfactant Protein mRNA Levels in Lambs

Cited by 10 publications

References 32 publications

Interaction between Surfactant and Ventilatory Support in Newborns with Primary Surfactant Deficiency

Interaction between Surfactant and Ventilatory Support in Newborns with Primary Surfactant Deficiency

A Systematic Review of the Influence of Continuous Positive Airway Pressure on Fetal and Newborn Animal Models: Suggestions to Improve Neonatal Respiratory Care

Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs

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