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

G. L. Chelucci, S. Boncinelli, M. Marsili, P. Lorenzi, A. Allegra, M. Linden, A. Chelucci, V. Merciai, F. Cresci, C. Rostagno, G. F. Gensini, A. Lockhart, J. Milic-Emili

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: 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. Design: 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. Measurements and results: Pulmonary and tissue gas exchange, pulmonary and systemic hemodynamics, respiratory system mechanics, TxB2 and 6-keto-PGF1α, 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 ≈1 in ASA-group compared to its fall to ≈0.7 in controls. Conclusion: 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.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalIntensive Care Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 1993

Keywords

  • Acute lung injury
  • Adult respiratory distress syndrome
  • Aspirin
  • Pulmonary and tissue gas exchange
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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