| Intrauterine inflammation causes pulmonary hypertension and cardiovascular sequelae in preterm lambs. | |
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MedLine Citation:
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PMID: 20339013 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chorioamnionitis increases the risk and severity of persistent pulmonary hypertension of the newborn in preterm infants. Exposure of preterm fetal lambs to intra-amniotic (IA) lipopolysaccharide (LPS) induces chorioamnionitis, causes hypertrophy of pulmonary resistance arterioles, and alters expression of pulmonary vascular growth proteins. We investigated the cardiopulmonary and systemic hemodynamic consequences of IA LPS in preterm lambs. Pregnant ewes received IA injection of LPS (n=6) or saline (controls; n=8) at 122 days gestation, 7 days before exteriorization, instrumentation, and delivery of the fetus with pulmonary and systemic flow probes and catheters at 129 days gestation. Newborn lambs were ventilated, targeting a tidal volume of 6-7 ml/kg and a positive end-expiratory pressure (PEEP) of 4 cmH2O. At 30 min, all lambs underwent a PEEP challenge: PEEP was increased by 2 cmH2O at 10-min intervals to 10 cmH2O and then decreased similarly to 4 cmH2O. Ventilation parameters, arterial blood flows, and pressures were recorded in real-time for 90 min. LPS lambs had higher total protein in bronchoalveolar lavage fluid (P<0.002), increased medial thickness of arteriolar walls (P=0.013), and right ventricular hypertrophy (P=0.012). Compared with controls, LPS lambs had worse oxygenation (P<0.001), decreased pulmonary blood flow (P=0.05), and higher pulsatility index (P<0.001) and pulmonary (P<0.001) and systemic arterial pressures (P=0.005) than controls. Intra-amniotic LPS increased right-to-left shunting across the ductus arteriosus (P=0.018) and decreased left ventricular output (P<0.001). We conclude that inflammation and pulmonary remodeling induced by IA LPS adversely alters pulmonary hemodynamics with subsequent cardiovascular and systemic sequelae, which may predispose the preterm lamb to persistent pulmonary hypertension of the newborn. |
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Authors:
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Graeme R Polglase; Stuart B Hooper; Andrew W Gill; Beth J Allison; Kelly J Crossley; Timothy J M Moss; Ilias Nitsos; J Jane Pillow; Martin Kluckow |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-25 |
Journal Detail:
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Title: Journal of applied physiology (Bethesda, Md. : 1985) Volume: 108 ISSN: 1522-1601 ISO Abbreviation: J. Appl. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-03 Completed Date: 2010-10-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8502536 Medline TA: J Appl Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 1757-65 Citation Subset: IM |
Affiliation:
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School of Women's and Infants' Health, The University of Western Australia, Crawley, Western Australia, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chorioamnionitis / physiopathology* Female Hypertension, Pulmonary / etiology*, physiopathology* Pregnancy Premature Birth / physiopathology* Sheep Ventricular Dysfunction, Left / etiology*, physiopathology* |
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