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Cardiopulmonary bypass is associated with altered vascular reactivity of isolated pulmonary artery in a porcine model: therapeutic potential of inhaled tezosentan.

Abstract：

OBJECTIVE:Whereas it is established that endothelin-1 elicits sustained deleterious effects on the cardiovascular system during cardiopulmonary bypass (CPB), presently it remains unknown whether the inhaled administration of the dual ETA and ETB antagonist tezosentan prevents the development of pulmonary endothelial dysfunction. DESIGN:A prospective, randomized laboratory investigation. SETTING:University research laboratory. PARTICIPANTS:Landrace swine. INTERVENTIONS:Three groups of animals underwent a 90-minute period of full bypass followed by a 60-minute period of reperfusion. Among treated groups, one received tezosentan through inhalation prior to CPB, whereas the other one received it intravenously at weaning from CPB; the third group remained untreated. Pulmonary vascular reactivity studies, realized on a total of 285 rings, were performed in all groups, including 1 sham. MEASUREMENTS AND MAIN RESULTS:The contractility of pulmonary arteries to prostaglandin F2α and to the thromboxane A2 mimetic U46619 was preserved in animals submitted to CPB. By contrast, there were significant increases both in the maximal contraction to endothelin-1 and in the plasma levels of the peptide 60 minutes after reperfusion. Tezosentan administered by inhalation or intravenously did not prevent the development of pulmonary CPB-associated endothelial dysfunction. However, while hemodynamic disturbances were improved with both routes, the inhaled administration had a beneficial effect on oxygen parameters over intravenous administration. CONCLUSIONS:Despite the blockade of the endothelin-1 pathway with tezosentan, the development of the pulmonary endothelial dysfunction associated with CPB still occurred. However, only the inhalation route had a significant impact on gas exchange during CPB.

journal_name

J Cardiothorac Vasc Anesth

journal_title

Journal of cardiothoracic and vascular anesthesia

authors

Mommerot A,Denault AY,Dupuis J,Carrier M,Perrault LP

doi

10.1053/j.jvca.2013.12.013

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

698-708

issue

eissn

1053-0770

issn

1532-8422

pii

S1053-0770(13)00680-0

journal_volume

pub_type

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Cardiopulmonary bypass is associated with altered vascular reactivity of isolated pulmonary artery in a porcine model: therapeutic potential of inhaled tezosentan.