Background:
Whereas the increase in endothelin-1 (ET-1) level occurring during cardiopulmonary bypass (CPB) elicits sustained deleterious effects on the cardiovascular system, it remains presently unknown whether it is the sole peptide implicated in the vasomotor alteration of the pulmonary tree and whether the blockade of its receptors may be beneficial.

Material and Methods:
Landrace swine were submitted to a 90 minute period of full bypass, followed by a 60 minute period of reperfusion; hemodynamic and biochemical parameters were assessed throughout the procedure. Vascular reactivity studies were performed on pulmonary coronary arteries in order to evaluate the implication of various vasocontracting agents; the role of ET-1 was further evaluated through measurements of its plasmatic levels. In a separate set of experiments, swine submitted to CPB were treated with tezosentan, a non-selective ETA and ETB blocker, by inhalational or intravenous route. Hemodynamic and vascular reactivity studies were performed.

Result:
Vascular reactivity studies demonstrated that the contractility of pulmonary arteries to prostaglandin F2α and to the prostaglandin H2 analog U46619 was preserved in the CPB group compared to sham. By contrast, the maximal contraction to ET-1 was significantly increased. The implication of the peptide was supported by a significant increase in plasmatic levels after the 60 minute period of reperfusion compared to baseline. In animals treated with tezosentan, hemodynamic disturbances such as poor oxygen exchange and increase in mean pulmonary artery pressure were prevented with inhaled and intravenous tezosentan. However, the development of pulmonary CPB-associated endothelial dysfunction was not prevented in both treated groups.

Conclusion:
thus, following CPB, an abnormal activation of the ET-1 transduction pathway may significantly contribute to the development of the pulmonary vasomotor alteration. Blockade of its action with a non-selective receptor antagonist prevent, depending on the route of administration, the hemodynamic impairments but not the pulmonary endothelial dysfunction, two factors contributing to the development of pulmonary hypertension.