Document Detail

Bosentan prevents hypoxia-reoxygenation-induced pulmonary hypertension and improves pulmonary function.
MedLine Citation:
PMID:  10585047     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  68     ISSN:  0003-4975     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  1999 Nov 
Date Detail:
Created Date:  1999-12-14     Completed Date:  1999-12-14     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1714-21; discussion 1721-2     Citation Subset:  AIM; IM    
Division of Pediatric Cardiothoracic Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
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MeSH Terms
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*
Vascular Resistance / drug effects*,  physiology
Reg. No./Substance:
0/Antihypertensive Agents; 0/Endothelin-1; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 0/Sulfonamides; 10102-43-9/Nitric Oxide; 7782-44-7/Oxygen; Q326023R30/bosentan

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