| Bosentan prevents hypoxia-reoxygenation-induced pulmonary hypertension and improves pulmonary function. | |
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MedLine Citation:
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PMID: 10585047 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Acute hypoxia results in increased pulmonary vascular resistance. Despite reoxygenation, pulmonary vascular resistance remains elevated and pulmonary function is altered. Endothelin-1 might contribute to hypoxia-reoxygenation-induced pulmonary hypertension and to reoxygenation injury by stimulating leukocytes. This study was carried out using an established model of hypoxia and reoxygenation to determine whether endothelin-1 blockade with Bosentan could prevent hypoxia-reoxygenation-induced pulmonary hypertension and reoxygenation injury. METHODS: Twenty neonatal piglets underwent 90 minutes of hypoxia, 60 minutes of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery. Control animals (n = 12) received no drug treatment, whereas the treatment group (n = 8) received the endothelin-1 receptor antagonist, Bosentan, throughout hypoxia. RESULTS: In controls, pulmonary vascular resistance increased during hypoxia to 491% of baseline and remained elevated after reoxygenation; however in the Bosentan group, it increased to only 160% of baseline by end-hypoxia, then decreased to 76% at end-recovery. Arterial endothelin-1 levels in controls increased to 591% of baseline after reoxygenation. Arterial nitrite levels decreased during hypoxia in controls but were maintained in the Bosentan group. Consequently, animals in the Bosentan group had better postreoxygenation pulmonary vascular resistance, A-a gradient, and airway resistance along with lower myeloperoxidase levels than controls. CONCLUSIONS: Acute hypoxia and postreoxygenation pulmonary hypertension was attenuated by Bosentan, which maintained nitric oxide levels during hypoxia, decreased leukocyte-mediated injury, and improved pulmonary function. |
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Authors:
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J M Pearl; S A Wellmann; J L McNamara; J P Lombardi; C J Wagner; J L Raake; D P Nelson |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Annals of thoracic surgery Volume: 68 ISSN: 0003-4975 ISO Abbreviation: Ann. Thorac. Surg. Publication Date: 1999 Nov |
Date Detail:
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Created Date: 1999-12-14 Completed Date: 1999-12-14 Revised Date: 2004-01-20 |
Medline Journal Info:
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Nlm Unique ID: 15030100R Medline TA: Ann Thorac Surg Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1714-21; discussion 1721-2 Citation Subset: AIM; IM |
Affiliation:
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Division of Pediatric Cardiothoracic Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. pearj0@chmcc.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Anoxia / physiopathology* Antihypertensive Agents / pharmacology* Cardiopulmonary Bypass Endothelin-1 / physiology Hypertension, Pulmonary / physiopathology* Nitric Oxide / physiology Oxygen / blood* Pulmonary Artery / drug effects, physiopathology Receptor, Endothelin A Receptors, Endothelin / antagonists & inhibitors, physiology Sulfonamides / pharmacology* Swine Vascular Resistance / drug effects*, physiology |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Endothelin-1; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 0/Sulfonamides; 10102-43-9/Nitric Oxide; 147536-97-8/bosentan; 7782-44-7/Oxygen |
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