Pulmonary perfusion during lipopolysaccharide (LPS) induced fetal endotoxemia in the preterm fetal sheep

Objective: To study endotoxin induced changes in pulmonary blood flow during normoxia and hypoxia and analyzed the role of nitric oxide (NO) and endothelin (ET) in this process. Study design: Twenty-seven fetal sheep were chronically instrumented at 107 +/- 1 days (term is 147 days). Experiments were performed 3 days after surgery. Fetuses were randomized into four groups. Group 1: control group (n = 5); Group 2: LPS group (n = 6) with lipopolysaccharide (LPS) injection at t-60 min; Group 3: L-NAME (it = 6) with nitro-L-arginine methyl ester (L-NAME) treatment at t-75 min; Group 4: L-NAME + LPS group (it = 6) with nitro-L-arginine methyl ester (L-NAME) pre-treatment at t-75 min and LPS administration at t-60 min as described above; Group 5: BQ123 + LPS group (17 = 4) with BQ123 Pre-treatment at t-75 min and LPS injection at t-60 min as described above. Results: Unlike in control fetuses, there was a marked elevation in pulmonary per-fusion in response to LPS induced endotoxemia during normoxia (+112%; p < 0.01), which was even further increased during hypoxia (+434%; p < 0.001). This increase was partially blocked by BQ123 (p < 0.05) and completely abolished by pre-treatment with L-NAME (p < 0.001). Conclusion: During fetal endotoxemia, pulmonary perfusion is increased by LPS induced production of nitric oxide. This may have a significant impact in the fetal inflammatory response syndrome, particularly in the inflammation of the fetal lungs observed in response to intrauterine infection. (c) 2005 Elsevier Ireland Ltd. All rights reserved.