Pulmonary vasoconstriction due to impaired nitric oxide production after cardiopulmonary bypass

Abstract

Pulmonary hypertension is a serious complication after cardiopulmonary bypass (CPB). This study tests the hypothesis that CPB provokes oxidant-mediated pulmonary endothelial dysfunction, leading to reduced nitric oxide (NO) production and pulmonary vasoconstriction. Twelve piglets underwent 2 hours of CPB. In 6 of them, CPB prime was supplemented with N-mercaptopropionylglycine and catalase, whereas the others were not treated. Left and right ventricular function were evaluated from end-systolic elastance and Starling analysis. Pulmonary vascular resistance and transpulmonary NO production (measuring NO2-, NO3-) were determined to assess pulmonary endothelial function. Cardiopulmonary bypass caused a significant increase in pulmonary vascular resistance (83 +/- 12 to 212 +/- 30 dynes.cm-5.s kg-1, p < 0.05), associated with a reduction of NO production (8.8 +/- 1.4 to 2.5 +/- 0.5 mumol/min, p < 0.05) and depressed right ventricular function (56 +/- 12% of control), whereas N-mercaptopropionylglycine and catalase added to the CPB allowed a substantial improvement of these deleterious effects of CPB. Cardiopulmonary bypass impairs pulmonary NO production, resulting in pulmonary vasoconstriction and right ventricular dysfunction, which can be reduced by antioxidants. These findings imply the validity of NO inhalation therapy for postoperative pulmonary hypertension as a supplementation of endogenous endothelium-derived relaxing factor.