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Mechanisms of protection against pulmonary hyperbaric O2 toxicity by intermittent air breaks

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Abstract

Intermittent exposure to air is used as a protective strategy against hyperbaric O2 (HBO2) toxicity. Little is known about optimal intermittent exposure schedules and the mechanism of protection. In this study, we examined the role of antioxidant enzymes, and inflammatory cytokines in the mechanism of HBO2 tolerance by intermittent air breaks. One group of rats was exposed continuously to 282 kPa O2 until death. Other groups were exposed to 30, 60, and 120 min intervals of HBO2 with different numbers of intermittent 30 min air breaks (1–12 breaks). After the final break, animals were exposed to HBO2 until death. In a separate experiment, animals were sacrificed before terminal exposure and lung tissues were collected for analysis of gene expression. Two intermittent schedules with 6 h cumulative O2 time (30/30 and 60/30 min schedules) were compared with continuous exposure to HBO2 for 6 h and with intermittent exposure of 8 h (120/30 min schedule) duration. Continuous exposure resulted in activation of inflammatory cytokine TNF-α and IL-1β mRNA expression, an increase in lung protein nitration and activation of inducible NOS (iNOS) mRNA. Inflammatory response was not observed at intermittent exposures of the same cumulative O2 time duration (30/30 and 60/30 min schedule). Expression of heme oxygenase-1 (HO-1) mRNA was significantly increased in all exposure groups while manganese superoxide dismutase (MnSOD) mRNA expression was increased only in continuous and 120/30 exposure groups. Results show that intermittent exposure to air protects against pulmonary HBO2 toxicity by inhibiting inflammation. The mechanism of inhibition may involve the antiinflammatory and antioxidative effect of HO-1 but some other mechanisms may also be involved in protection by intermittent air breaks.

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Acknowledgments

This work was supported by Office of Naval Research Work Unit #62236N.04122.1343.A0502. The opinions expressed herein are those of the authors and do not reflect the official policy of the Department of Navy, Department of Defense, of the US Government.

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Correspondence to Mikulas Chavko.

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Chavko, M., Mahon, R.T. & McCarron, R.M. Mechanisms of protection against pulmonary hyperbaric O2 toxicity by intermittent air breaks. Eur J Appl Physiol 102, 525–532 (2008). https://doi.org/10.1007/s00421-007-0611-8

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