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Am J Respir Crit Care Med. 2008 Aug 15;178(4):399-406. doi: 10.1164/rccm.200711-1631OC. Epub 2008 May 29.

Blunted hypoxic pulmonary vasoconstriction in experimental neonatal chronic lung disease.

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  • 1Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Abstract

RATIONALE:

Neonatal chronic lung disease (CLD), caused by prolonged mechanical ventilation (MV) with O(2)-rich gas, is the most common cause of long-term hospitalization and recurrent respiratory illness in extremely premature infants. Recurrent episodes of hypoxemia and associated ventilator adjustments often lead to worsening CLD. The mechanism that causes these hypoxemic episodes is unknown. Hypoxic pulmonary vasoconstriction (HPV), which is partially controlled by O(2)-sensitive voltage-gated potassium (K(v)) channels, is an important adaptive response to local hypoxia that helps to match perfusion and ventilation in the lung.

OBJECTIVES:

To test the hypothesis that chronic lung injury (CLI) impairs HPV.

METHODS:

We studied preterm lambs that had MV with O(2)-rich gas for 3 weeks and newborn rats that breathed 95%-O(2) for 2 weeks, both of which resulted in airspace enlargement and pulmonary vascular changes consistent with CLD.

MEASUREMENTS AND MAIN RESULTS:

HPV was attenuated in preterm lambs with CLI after 2 weeks of MV and in newborn rats with CLI after 2 weeks of hyperoxia. HPV and constriction to the K(v)1.x-specific inhibitor, correolide, were preferentially blunted in excised distal pulmonary arteries (dPAs) from hyperoxic rats, whose dPAs exhibited decreased K(v)1.5 and K(v)2.1 mRNA and K(+) current. Intrapulmonary gene transfer of K(v)1.5, encoding the ion channel that is thought to trigger HPV, increased O(2)-sensitive K(+) current in cultured smooth muscle cells from rat dPAs, and restored HPV in hyperoxic rats.

CONCLUSIONS:

Reduced expression/activity of O(2)-sensitive K(v) channels in dPAs contributes to blunted HPV observed in neonatal CLD.

PMID:
18511704
PMCID:
PMC2542441
DOI:
10.1164/rccm.200711-1631OC
[PubMed - indexed for MEDLINE]
Free PMC Article
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