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Pharmacological intervention to the inflammatory response from decompression sickness in rats.

Author(s): Little T, Butler BD

Affiliation(s): Baromedical Laboratory, Department of Anesthesiology, The University of Texas Medical School, Houston, TX 77030, USA.

Publication date & source: 2008-02, Aviat Space Environ Med., 79(2):87-93.

Publication type: Research Support, U.S. Gov't, Non-P.H.S.

INTRODUCTION: Venous bubbles resulting from experimental decompression sickness (DCS) may cause an inflammatory-like reaction with activation of granulocytes and release of metabolites from arachidonic acid. The release of cyclooxygenase and lipoxygenase pathway mediated metabolites, namely thromboxane B2 (TXB2) and leukotriene E4 (LTE4) likely contribute to this overall DCS response. In the present study we examined the effect on DCS outcome of several agents affecting both pathways. METHODS: Indomethacin and acetylsalicylic acid were administered to study the cyclooxygenase pathway mediators, Zafirlukast and Zileuton to study inhibition of the lipoxygenase pathway, and isoproterenol for its beta-agonist effects. The agents were administered to randomly selected Sprague-Dawley rats prior to compression to 683 kPa for 60 min. Following 60 min recovery post-decompression, DCS evaluation included: gross symptoms; pulmonary edema; bronchoalveolar lavage and pleural fluid protein; white blood cell and differential cell counts; and urine, bronchoalveolar lavage, and plasma TXB2 and LTE4 analysis. RESULTS: The results indicate that both Zafirlukast and Zileuton reduced the reported DCS symptoms, pulmonary edema, pleural and bronchoalveolar lavage protein levels, white blood cell counts in the pleural and bronchoalveolar lavage, and leukotriene levels in the bronchoalveolar lavage vs. that of vehicle-treated rats exposed to compression/decompression. The effect of these agents on pleural and bronchial alveolar protein levels demonstrated protective effects on microvascular permeability. Acetylsalicylic acid and indomethacin treatment had less effect on reducing inflammatory-induced changes. DISCUSSION: The effect of inflammatory-like responses to DCS can be altered with pharmacological intervention given prior to compression.

Page last updated: 2008-03-26

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