Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20-28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28degreesC core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 mug/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO(2)) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0 +/- 5.3 nmol/g of tissue rose to 67.6 +/- 5.7 nmol/g of tissue after weaning from CPB in group I (P = 0.028). In group II MDA values also increased from 43.1 +/- 4.3 to 52.4 +/- 5.7 nmol MDA/g of tissue after weaning from CPB (P = 0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P = 0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1 +/- 0.2, significantly lower than in the control group (6.8 +/- 0.4), (P = 0.01). AaDO(2) increased significantly in group I (P = 0.028). There was no statistically significant difference (P = 0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P < 0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass. (C) 2003 Elsevier Science B.V. All rights reserved.