• J M Pearl, S A Wellmann, J L McNamara, J P Lombardi, C J Wagner, J L Raake, and D P Nelson.
• Division of Pediatric Cardiothoracic Surgery, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. pearj0@chmcc.org
• Ann. Thorac. Surg. 1999 Nov 1; 68 (5): 1714-21; discussion 1721-2.

BackgroundAcute 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.MethodsTwenty 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.ResultsIn 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.ConclusionsAcute 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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