Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport*

Kaskinen, Anu; Helve, Otto; Andersson, Sture; Kirjavainen, Turkka; Martelius, Laura; Mattila, Ilkka; Rautiainen, Paula; Pitkänen, Olli

doi:10.1097/pcc.0000000000000568

Cited by 11 publications

(20 citation statements)

References 38 publications

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“…Cytokeratin 18 (CK18) and β1‐Na‐K‐ATPase primers and probes were designed using the Primer Blast and Beacon designer. Relative amounts of mRNAs were calculated according to the ΔΔCq‐algorithm using the epithelial cell–specific CK18 as an endogenous reference gene for normalization …”

Section: Methodsmentioning

confidence: 63%

“…Post‐expression regulation of the ion transporters is essential, but its study is primarily limited to in vitro settings. In humans, the gene expression associates with the channel function . Nevertheless, larger studies combining different methods of study of lung fluid clearance during adaptation are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Airway epithelial cell samples from the nasal epithelium were collected at three time points: 2 (0‐6) min, 1.3 (0.8‐2.9) h, and 25.5 (24.0‐30.4) h [median (range)] postnatally with a sterile probe (RhinoProbe, Arlington Scientific, Springville, UT). Time points were designated as 2 min, 1 h, and 24 h. RNA isolation (RNeasy, Qiagen, Valencia, CA) as well as its spectrophotometric quantitation (NanoDrop, ThermoFisher, Wilmington, DE) were performed as previously described …”

Section: Methodsmentioning

confidence: 99%

“…We performed the reverse transcription of epithelial cell RNA and PCR of cDNA as previously described . Samples containing genomic DNA were omitted.…”

Section: Methodsmentioning

confidence: 99%

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Postnatal gene expression of airway epithelial sodium transporters associated with birth stress in humans

Süvari

Janér

Helve

et al. 2019

Pediatric Pulmonology

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Introduction Lung fluid clearance is essential for successful postnatal pulmonary adaptation. The epithelial sodium channel (ENaC) and Na‐K‐ATPase, induced by serum‐ and glucocorticoid‐inducible kinase 1 (SGK1) as well as aquaporins (AQP), represent key players in the switch from fetal lung fluid secretion to absorption and in early postnatal lung fluid balance. Birth stress, including a surge in catecholamines, promotes pulmonary adaptation, likely through the augmentation of epithelial sodium reabsorption. Objectives We sought to determine the changes in the airway gene expression of molecules vital to epithelial sodium transport during early pulmonary adaptation, and the association with birth stress reflected in the norepinephrine concentration in the cord blood in humans. Methods We included 70 term newborns: 28 born via vaginal delivery and 42 via elective cesarean section. We determined the norepinephrine concentrations in the cord blood using tandem mass spectrometry and collected nasal epithelial cell samples at 2 min, 1 h, and 24 h postnatally to quantify ENaC, Na‐K‐ATPase, AQP5, and SGK1 mRNAs using RT‐PCR. Results The molecular gene expression involved in airway epithelium sodium transport changed markedly within the first hour postnatally. Newborns born via elective cesarean section exhibited a lower expression of ENaC, Na‐K‐ATPase, and SGK1. Significant correlations existed between the expressions of ENaC, Na‐K‐ATPase, and SGK1, and the concentration of norepinephrine in the cord blood. Conclusions The association of ENaC, Na‐K‐ATPase, and SGK1 expression with the cord blood norepinephrine concentration points to the importance of birth stress in promoting lung fluid clearance during early postnatal pulmonary adaptation.

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Section: Methodsmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…We performed the reverse transcription of epithelial cell RNA and PCR of cDNA as previously described . Samples containing genomic DNA were omitted.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Postnatal gene expression of airway epithelial sodium transporters associated with birth stress in humans

Süvari

Janér

Helve

et al. 2019

Pediatric Pulmonology

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“…To distinguish them, either amiloride, a specific blocker of ENaC, or Na + -free saline was used to eliminate NPD following positive charge flow 16 17 . To investigate Cl − secretion or CFTR activity, either Cl − -free Ringer solution or a cAMP-elevating compound was added to the perfusate 18 19 .…”

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confidence: 99%

Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury

Zhu

et al. 2016

Sci Rep

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Nasal potential difference (NPD), a well-established in vivo clinical test for cystic fibrosis, reflects transepithelial cation and anion transport in the respiratory epithelium. To analyze whether NPD can be applied to diagnose hypoxic lung injury, we searched PubMed, EMBASE, Scopus, Web of Science, Ovid MEDLINE, and Google Scholar, and analyzed data retrieved from eleven unbiased studies for high altitude pulmonary edema (HAPE) and respiratory distress syndrome (RDS) using the software RevMan and R. There was a significant reduction in overall basal (WMD −5.27 mV, 95% CI: −6.03 to −4.52, P < 0.00001, I2 = 42%), amiloride-sensitive (ENaC) (−2.87 mV, 95% CI: −4.02 to −1.72, P < 0.00001, I2 = 51%), and -resistant fractions (−3.91 mV, 95% CI: −7.64 to −0.18, P = 0.04, I2 = 95%) in lung injury patients. Further analysis of HAPE and RDS separately corroborated these observations. Moreover, SpO2 correlated with ENaC-associated NPD positively in patients only, but apparently related to CFTR-contributed NPD level inversely. These correlations were confirmed by the opposite associations between NPD values and altitude, which had a negative regression with SpO2 level. Basal NPD was significantly associated with amiloride-resistant but not ENaC fraction. Our analyses demonstrate that acute lung injury associated with systemic hypoxia is characterized by dysfunctional NPD.

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Glucocorticoids, sodium transport mediators, and respiratory distress syndrome in preterm infants

et al. 2020

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Background Antenatal glucocorticoids (GCs) reduce respiratory distress syndrome (RDS) in preterm infants and are associated with reduced lung liquid content. Our aim was to assess whether airway gene expression of mediators of pulmonary epithelial sodium and liquid absorption, and further, respiratory morbidity, associate with cord blood GC concentrations. Methods The study included 64 infants delivered <32 weeks gestation. Cortisol and betamethasone in umbilical cord blood were quantified with liquid chromatography-tandem mass spectrometry. The total GC concentration was calculated. Gene expression of the epithelial sodium channel (ENaC), Na,K-ATPase, and serum- and GC-inducible kinase 1 at <2 h and at 1 day postnatally in nasal epithelial cell samples was quantified with reverse transcription-polymerase chain reaction. The mean oxygen supplementation during the first 72 h was calculated. Results Concentrations of cord blood betamethasone and total GC were significantly lower in infants with RDS and correlated with mean oxygen supplementation. Expression of αENaC and α1- and β1Na,K-ATPase at <2 h correlated with betamethasone and total GC concentrations. Expression of Na,K-ATPase was lower in infants with RDS. Conclusion Enhancement of lung liquid absorption via increased expression of sodium transporters may contribute to the beneficial pulmonary effects of antenatal GCs. Impact RDS is related to lower umbilical cord blood GC concentrations and lower airway expression of sodium transporters. In addition to the timing of antenatal GC treatment, resulting concentrations may be of importance in preventing RDS. Induction of sodium transport may be a factor contributing to the pulmonary response to antenatal GCs.

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Chronic Hypoxemia in Children With Congenital Heart Defect Impairs Airway Epithelial Sodium Transport*

Abstract: The impaired airway epithelial amiloride-sensitive Na transport activity in profoundly hypoxemic children with cyanotic congenital heart defect may hinder defense against lung edema after cardiac surgery.

Cited by 11 publications

References 38 publications

Postnatal gene expression of airway epithelial sodium transporters associated with birth stress in humans

Postnatal gene expression of airway epithelial sodium transporters associated with birth stress in humans

Systematic review and meta-analysis of nasal potential difference in hypoxia-induced lung injury

Glucocorticoids, sodium transport mediators, and respiratory distress syndrome in preterm infants

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