Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons

Meredith, Keith S.; deLemos, Robert A.; Coalson, Jacqueline J.; King, Richard J.; Gerstmann, Dale R.; Kumar, Rakesh; Kuehl, Thomas J.; Winter, D. C.; Taylor, Alfred; Clark, Reese H.

doi:10.1152/jappl.1989.66.5.2150

Cited by 204 publications

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“…Although many animal models of BPD have been described (9)(10)(11)(12)(13)(14)(15), BPD in preterm baboons is most similar to human BPD clinically and pathologically. The original hyperoxic BPD model was in animals at 140 days' gestation (term 5 180 d) given 100% O 2 for 10 days (140-day 100%) (16,17), which develop acute respiratory distress syndrome followed by severe BPD similar to old BPD (18).…”

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confidence: 99%

Bombesin-like Peptides Modulate Alveolarization and Angiogenesis in Bronchopulmonary Dysplasia

Subramaniam

Bausch

Twomey

et al. 2007

Am J Respir Crit Care Med

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Rationale: The incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns, is paradoxically rising despite medical advances. We demonstrated elevated bombesin-like peptide levels in infants that later developed BPD. In the 140-day hyperoxic baboon model of BPD, anti-bombesin antibody 2A11 abrogated lung injury. Objectives: To test the hypothesis that bombesin-like peptides mediate BPD in extremely premature baboons (born at Gestational Day 125 and given oxygen pro re nata [PRN], called the 125-day PRN model), similar to ''modern-day BPD.'' Methods: The 125-day animals were treated with 2A11 on Postnatal Day 1 (P1), P3, and P6. On P14 and P21, lungs were inflation-fixed for histopathologic analyses of alveolarization. Regulation of angiogenesis by bombesin was evaluated using cultured pulmonary microvascular endothelial cells. Measurements and Main Results: In 125-day PRN animals, urine bombesinlike peptide levels at P2-3 are directly correlated with impaired lung function at P14. Gastrin-releasing peptide (the major pulmonary bombesin-like peptide) mRNA was elevated eightfold at P1 and remained high thereafter. At P14, 2A11 reduced alveolar wall thickness and increased the percentage of secondary septa containing endothelial cells. At P21, 2A11-treated 125-day PRN animals had improved alveolarization according to mean linear intercepts and number of branch points per millimeter squared. Bombesin promoted tubulogenesis of cultured pulmonary microvascular endothelial cells, but cocultured fetal lung mesenchymal cells abrogated this effect. Conclusions: Early bombesin-like peptide overproduction in 125-day PRN animals predicted alveolarization defects weeks later. Bombesinlike peptide blockade improved septation, with the greatest effects at P21. This could have implications for preventing BPD in premature infants.Keywords: bombesin; gastrin-releasing peptide; mechanical ventilation; prematurity; antibody treatment Bronchopulmonary dysplasia (BPD) is a chronic lung disease of newborns, often following respiratory distress syndrome. The etiology of BPD remains enigmatic, although it has been associated with multiple factors, including mechanical ventilation, oxygen therapy, infection, inflammatory mediators, and immaturity (1-3). ''Old BPD,'' described by Northway (4), was characterized by airway injury, inflammation, segments of atelectasis alternating with cystic overexpansion, and interstitial fibrosis. Such severe BPD is now less prevalent due to improved medical care. However, BPD is still a major burden in pediatric medicine, paradoxically due to success in improving acute survival. BPD affects approximately 30% of infants weighing less than 1,000 g. ''Modernday BPD,'' occurring in infants less than 30 weeks' gestation, seems to have a different pathophysiology and is characterized by arrested alveolar development and microvascular defects (3,(5)(6)(7)(8).Although many animal models of BPD have been described (9-15), BPD in preterm baboons is most similar to human BPD clinically and path...

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confidence: 99%

Bombesin-like Peptides Modulate Alveolarization and Angiogenesis in Bronchopulmonary Dysplasia

Subramaniam

Bausch

Twomey

et al. 2007

Am J Respir Crit Care Med

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“…5,6 In premature baboon models of hyaline membrane disease, high-frequency oscillatory ventilation (HFOV) results in more uniform lung inflation pattern, improves oxygenation, and reduces the severity of lung pathology produced by assisted ventilation. 7,8 Surprisingly the first multicenter randomized trial of HFOV versus CV by the HIFI Study Group 9 failed to show any benefit in decreasing the frequency of CLD. On the contrary, it showed an increased incidence of intraventricular hemorrhage (IVH) and neurodevelopmental abnormalities at follow-up.…”

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confidence: 99%

Elective High-frequency Oscillatory Ventilation Versus Conventional Ventilation in Preterm Infants With Pulmonary Dysfunction: Systematic Review and Meta-analyses

Bhuta

Henderson‐Smart

1997

Pediatrics

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ABSTRACT. Objectives. To systematically review the evidence to determine whether the routine use of highfrequency oscillatory ventilation (HFOV) as compared with conventional ventilation (CV) is beneficial or harmful in preterm infants requiring mechanical ventilation for pulmonary failure principally due to respiratory distress syndrome.Methods. All randomized controlled trials of elective HFOV versus CV in preterm infants <36 weeks' gestation with respiratory failure mainly attributable to respiratory distress syndrome were identified from the literature through a search of MEDLINE, EMBASE, Oxford database of Perinatal trials, and previous reviews including cross-references and abstracts. Meta-analyses using event rate ratios (ERR), event rate difference, and if significant, number needed-to-treat were calculated (95% confidence limits were used for all analyses). Two prespecified subgroup analyses were performed.Results. Four published trials 9,18 -20 were included. Meta-analyses revealed the following ERR (95% confidence intervals) for HFOV versus CV 19Conclusions. The overall meta-analysis is dominated by the HIFI study, 9 which was criticized for its methodology 11 and surfactant was not used. Subsequent studies, most of which used HVS and/or surfactant, have shown benefits in measures of CLD without an increase in rates of IVH. Caution is warranted in interpreting these results because: 1) the treatment is not blinded and this could affect some outcomes; 2) except for one small trial 20 postneonatal survival, lung function, and neurodevelopment have not been reported from HVS trials; and 3) the benefits and disadvantages have not been reported in infants born at different gestational ages or different birth weights. Importantly, results from groups experienced in the use of HFOV may not be readily generalizable. Pediatrics 1997;100(5). URL: http://www.pediatrics.org/ cgi/content/full/100/5/e6; meta-analyses, high-frequency ventilation, high-frequency oscillatory ventilation, chronic lung disease, preterm, neonatal ventilation, neonatal morbidity.

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“…The biological significance of this finding can only be elucidated in further studies applying the present findings to established models of pulmonary disease in which HFOV is known to be beneficial (Hamilton et al 1983;McCulloch et al 1988;Meredith et al 1989). The benefits of HFOV have traditionally been explained by its potential to optimize lung expansion, thus avoiding both atelectasis and overdistension (Greenough, 1994;Froese, 1997).…”

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confidence: 82%

“…HFOV is now commonly used to alleviate neonatal pulmonary diseases (Greenough, 1994;Ring & Stidham, 1994;Gerstmann et al 1996). Concomitant with improved pulmonary mechanics, a reduction in inspired oxygen concentration and a reduction in structural injury in comparison with conventional ventilation were demonstrated in experimental studies (Hamilton et al 1983;McCulloch et al 1988;Meredith et al 1989). The present study compared the effects of HFOV and intermittent mandatory ventilation (IMV) on NO homeostasis in the lower airways of healthy rabbits.…”

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confidence: 99%

Exhaled Nitric Oxide Increases During High Frequency Oscillatory Ventilation in Rabbits

Artlich¹,

Adding²,

Agvald³

et al. 1999

Exp. Physiol.

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summaryThis study compared the effects of high frequency oscillatory ventilation (HFOV) and intermittent mandatory ventilation (IMV) on the homeostasis of nitric oxide (NO) in the lower respiratory tract of healthy rabbits. The mechanisms underlying a putative stretch response of NO formation in the airways were further elucidated. Male New Zealand White rabbits were anaesthetized, tracheotomized and ventilated with IMV or HFOV in random order. Total NO excretion increased from 9·6 ± 0·8 nl min¢ (mean ± s.e.m.) during IMV to 22·6 ± 2·7 nl min¢ during HFOV (P < 0·001). This increase was not explained by changes of functional residual capacity (ÄFRC). A similar increase in NO excretion during HFOV was seen in isolated buffer-perfused lungs under constant circulatory conditions (P < 0·05, n = 4). Intratracheal mean COµ and NO concentrations, measured at 2·5, 5, 7·5 and 10 cm below tracheostomy, increased significantly with increasing distance into the lung during both IMV and HFOV (P < 0·001 for each comparison). At every intratracheal location of the sampling catheter, particularly low in the airways, both COµ and NO concentrations were significantly higher during HFOV than during IMV (P < 0·01 for each comparison). We conclude that HFOV increases pulmonary NO production in healthy rabbits. Increased stretch activation of the respiratory system during HFOV is suggested as a possible underlying mechanism. The increase in mean airway NO concentrations may have biological effects in the respiratory tract. Whether it can account for some of the benefits of HFOV treatment needs to be considered. introduction NO, which is continuously produced within the lower respiratory tract (Gustafsson et al. 1991;Persson et al. 1993), can be detected in the exhaled gas of most mammalian species, offering a unique possibility to study features of NO metabolism non-invasively (Gustafsson, 1997). However, the anatomic site and main cell type producing those NO molecules detected in exhaled gas is still a matter of debate (Gustafsson, 1997). Thus the extent to which the various biological functions of NO are reflected in the concentration of NO in exhaled gas merits further study. Moreover, factors influencing the amount of NO detected in exhaled gas are only beginning to evolve. We have recently shown in rabbits and guinea-pigs that lower airway NO formation is suppressed by high airway concentrations of COµ Str omberg et al. 1997;Adding et al. 1999). This rapid effect is also present in isolated buffer-perfused rabbit lungs and cannot be explained by either altered sympathetic outflow or changes of extracellular pH (Adding et al. 1999). Another mechanism to increase lower airway NO formation is revealed during increases of positive end-expiratory pressure (PEEP)

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Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboons

Cited by 204 publications

References 0 publications

Bombesin-like Peptides Modulate Alveolarization and Angiogenesis in Bronchopulmonary Dysplasia

Bombesin-like Peptides Modulate Alveolarization and Angiogenesis in Bronchopulmonary Dysplasia

Elective High-frequency Oscillatory Ventilation Versus Conventional Ventilation in Preterm Infants With Pulmonary Dysfunction: Systematic Review and Meta-analyses

Exhaled Nitric Oxide Increases During High Frequency Oscillatory Ventilation in Rabbits

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