Inhalation of nitric oxide as a treatment of pulmonary hypertension in congenital diaphragmatic hernia

Henneberg, Steen Winther; Jepsen, S; Andersen, P. K.; Pedersen, Sidsel Arnspang

doi:10.1016/0022-3468(95)90763-7

Cited by 37 publications

(8 citation statements)

References 21 publications

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“…Although newer treatment modalities, including high-frequency ventilation, extracorporeal membrane oxygenation, surfactant therapy, and nitric oxide inhalation, have been introduced in an attempt to improve survival in patients with CDH, the mortality in this condition still remains high (1,2).…”

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confidence: 99%

Antenatal Dexamethasone Administration Increases Fetal Lung DNA Synthesis and RNA and Protein Content in Nitrofen-Induced Congenital Diaphragmatic Hernia in Rats

et al. 2000

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Antenatal glucocorticoids treatment has been shown to correct pulmonary immaturity. The thymidine analog bromodeoxyuridine (BrdU) is incorporated into S-phase cells and used as a marker of DNA synthesis. In this study, we investigated the effect of antenatal glucocorticoid administration on DNA synthesis and RNA and protein content in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats to better understand the effect of antenatal glucocorticoids on CDH lung. The CDH model was induced in pregnant rats using nitrofen. Dexamethasone (0.25 mg/kg) was given on d 18.5 and 19.5 of gestation (term ϭ 22 d). BrdU was administered 1 h before fetuses were killed on d 21, and detected by immunohistochemistry. DNA synthesis was evaluated by percentage of BrdU-incorporated nuclei (BrdU labeling index). Total RNA and soluble protein were extracted from another set of left lungs to measure RNA and protein content. BrdU labeling index and total RNA content were significantly decreased in CDH lung compared with control rats. Antenatal dexamethasone treatment significantly increased BrdU labeling index and RNA and protein content in the left CDH lung. Our findings of decreased DNA synthesis and decreased RNA and protein content in CDH lung suggest that lung growth and development are suppressed in hypoplastic CDH lung. Increased DNA synthesis and increased RNA and protein content in dexamethasone-treated CDH lung suggest that antenatal glucocorticoids may accelerate fetal lung growth and development in CDH. The high mortality in patients with CDH has been shown to be the result of pulmonary hypoplasia and persistent pulmonary hypertension (1). Although newer treatment modalities, including high-frequency ventilation, extracorporeal membrane oxygenation, surfactant therapy, and nitric oxide inhalation, have been introduced in an attempt to improve survival in patients with CDH, the mortality in this condition still remains high (1, 2).Recent improvements in antenatal sonography have resulted in a large number of CDH cases being diagnosed antenatally (3), which provided a possibility of antenatal treatment for severe CDH patients. Recently, antenatal administration of glucocorticoid has been proposed as a noninvasive modality in promoting fetal lung maturation and differentiation. Several control trials have shown the beneficial effects of antenatal glucocorticoid therapy as a means of promoting lung maturation and preventing respiratory distress syndrome in premature human newborns (4, 5). In experimentally produced CDH in animals, it has been reported that antenatal glucocorticoid treatment improves surfactant biochemical immaturity, increases lung compliance and distensibility, enhances lung morphology, and reduces pulmonary vascular adventitial and medial thickness (6 -11). The exact mechanism by which antenatal glucocorticoid therapy improves pulmonary immaturity in CDH is not fully understood.BrdU is a thymidine analog that is incorporated into the newly replicated DNA of S-phase cells. Since an antibody specific for...

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Antenatal Dexamethasone Administration Increases Fetal Lung DNA Synthesis and RNA and Protein Content in Nitrofen-Induced Congenital Diaphragmatic Hernia in Rats

et al. 2000

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“…We also found that 25% failed INO therapy, most likely as a result of severe pulmonary hypoplasia seen in CDH, and severe lung damage due to severe hypoxia as in asphyxia and RDS. A number of studies have noted a general lack of a sustained improvement in oxygenation in response to INO in the management of CDH [12,13,14]. In this study ECMO was not used as an alternative therapy for the INO non-responders because it was not available in our hospital for neonates.…”

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confidence: 99%

Inhaled nitric oxide in persistent pulmonary hypertension of the newborn refractory to high-frequency ventilation

Al‐Alaiyan

Neiley

1999

Crit Care

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Background:This study was designed to evaluate the effect of nitric oxide (NO) on the management of neonates with severe persistent pulmonary hypertension refractory to high-frequency oscillatory ventilation.Methods:The birth weight and the gestational age of infants were 3125.5 ± 794 g (mean ± SD) and 39 ± 2.4 weeks, respectively. All neonates were ventilated for an average of 137.5 min (range 90-180 min) prior to NO therapy. The mean oxygenation index (OI) of all neonates prior to NO was 46.3 ± 5 (mean ± SEM). NO was initially administered at 20 parts per million (ppm) for at least 2 h and increased gradually by 2 ppm to a maximum of 80 ppm.Results:Eighteen infants (75%) responded and six (25%) did not respond to the treatment. Three neonates died in the responding group, while all the non-responders died (P = 0.0001). The survival rate was 62.5% among all neonates. NO significantly decreased OI (P < 0.0001) and improved the arterial/alveolar (a/A) oxygen ratio (P < 0.0001) within the first 2 h of NO therapy in 61.1% of the responders. However, the OI and the a/A oxygen ratio remained almost the same throughout the treatment in the non-responders and the non-survivors.Conclusion:Inhaled NO at 20 ppm, following adequate ventilation for 2 h without significant response, could be used to identify the majority of the non-responders in order to seek other alternatives.

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“…166 Inhalation of NO has been used successfully in a few CDH patients, and it has been proposed that NO may be an alternative for ECMO in some cases. [167][168][169] Karamanoukian and coworkers reported that NO only had a positive effect in five CDH patients studied after decanulation from ECMO, but not in patients who had been treated with NO before ECMO. 170 The same group described that oxygenation could only be improved in fetal lambs when inhaled NO was combined with exogenous surfactant.…”

Section: Therapy Focusing On Lowering the Pulmonary Vascular Tonementioning

confidence: 99%

The lungs in congenital diaphragmatic hernia: Do we understand?

IJsselstijn

Tibboel

1998

Pediatr. Pulmonol.

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Inhalation of nitric oxide as a treatment of pulmonary hypertension in congenital diaphragmatic hernia

Cited by 37 publications

References 21 publications

Antenatal Dexamethasone Administration Increases Fetal Lung DNA Synthesis and RNA and Protein Content in Nitrofen-Induced Congenital Diaphragmatic Hernia in Rats

Antenatal Dexamethasone Administration Increases Fetal Lung DNA Synthesis and RNA and Protein Content in Nitrofen-Induced Congenital Diaphragmatic Hernia in Rats

Inhaled nitric oxide in persistent pulmonary hypertension of the newborn refractory to high-frequency ventilation

The lungs in congenital diaphragmatic hernia: Do we understand?

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