Aspirin effect on early and late changes in acute lung injury in sheep

There have been several studies that have already explored the potential beneficial role of cyclo-oxygenase (CO) inhibitors on oleic acid (OA)-induced lung injury in different species. These studies report no significant effect of CO inhibition, though thromboxane B2 (TxB2) was effectively blocked. However, recent studies indicate that pre-treatment with aspirin (ASA) preserve gas exchange in OA lung injury in dogs. Aim of our study has been to evaluate the potential beneficial effects of the pre-treatment with low doses of ASA on gas exchange, hemodynamics, respiratory mechanics, prostanoids and lung histology in OA-induced lung injury in sheep.

0.09 ml/kg of OA was administered into the right atrium of 14 anaesthetized sheep. Six received a bolus of ASA (10 mg/kg i.v.) 30 min before OA, the others saline as placebo.

Pulmonary and tissue gas exchange, pulmonary and systematic hemodynamics, respiratory system mechanics, TxB2 and 6-keto-PGF1 alpha, leukocytes and platelets concentrations were measured throughout the subsequent 3 h and lung histology was effected at end-experiment. The principal findings of our study are: 1) ASA reduces OA-induced early pulmonary vasoconstriction and bronchoconstriction, parallelled by a suppression of TxB2 generation; 2) the late increase in pulmonary artery pressure and airway resistance due to OA is not inhibited by ASA; 3) the early disturbance in pulmonary gas exchange is reduced by ASA, whereas the late severe deterioration is exaggerated by ASA; 4) the stability of tissue exchange ratio (R) at approximately 1 in ASA-group compared to its fall to approximately 0.7 in controls.

Our findings suggest that ASA: 1) is only effective to treat the very transient TxB2-induced pulmonary vasoconstriction resulting in hydrostatic edema, and it is ineffective, even accentuates, the subsequent major pulmonary endothelial cell injury leading to alveolar flooding that is unrelated to TxB2; 2) has a transient protective effect on the TxB2-induced early bronchospasm; 3) has a biphasic behaviour on gas exchange, with a benefit which lasts only one hour and then results in a worse gas exchange; 4) has an immediate, stabilizing, persisting effect on R, contrasting with its transient effect on pulmonary hemodynamics and PaO2.