Protective effect of antioxidants on pulmonary endothelial function after cardiopulmonary bypass

Objectives: Pulmonary endothelium-dependent vasodilation is impaired after cardiopulmonary bypass. One explanation might be the generation of reactive oxygen species during the period without flow in the pulmonary artery. The aim of the current study was to investigate if treatment with antioxidants could improve pulmonary endothelial function after cardiopulmonary bypass and influence the blood oxidative status. Design: A prospective, randomized, double-blind study. Setting: The operating room, intensive care unit, and the biochemistry laboratory in University Hospitals. Participants: Patients scheduled for cardiac surgery with cardiopulmonary bypass. Interventions: Treatment with vitamin E, vitamin C, allopurinol, and acetylcysteine (n = 12) or placebo (n = 10). Measurements and Main Results: The pulmonary reactivity to an infusion of acetylcholine and markers of oxidative stress in blood were measured before and after cardiopulmonary bypass. Sixteen control patients received saline instead of acetylcholine. Before surgery the pulmonary vascular resistance index decreased during infusion of acetylcholine by 24% and 21% in the treatment and placebo groups. After surgery the decrease was 20% and 8%, respectively, (p = 0.422 and p = 0.026) compared with preoperative response. Pulmonary vasodilation induced by acetylcholine was better maintained in the group treated with antioxidants (p = 0.048). In the treatment group, the blood concentrations of early intermediates of lipid peroxidation were higher, but not that of the end products. Glutathione and oxidized glutathione increased after cardiopulmonary bypass in the treatment group. Conclusion: The better maintained endothelium-dependent vasodilation after cardiopulmonary bypass in the treatment group indicated that antioxidant therapy reduced endothelial dysfunction. (C) 2003 Elsevier Inc. All rights reserved.