Response of antioxidant enzymes to intermittent and continuous hyperbaric oxygen

Rats and guinea pigs were exposed to O2 at 2.8 ATA (HBO) delivered either continuously or intermittently (repeated cycles of 10 min of 100% O2 followed by 2.5 min of air). The O2 time required to produce convulsions and death was increased significantly in both species by intermittency. To determine whether changes in brain and lung superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx) correlated with the observed tolerance, enzyme activities were measured after short or long HBO exposures. For each exposure duration, one group received continuous and one intermittent HBO; O2 times were matched. HBO had marked effects on these enzymes: lung SOD increased (guinea pigs 47%, rats 88%) and CAT and GSHPx activities decreased (33%) in brain and lung. No differences were seen in lung GSHPx or brain CAT in rats or brain SOD in either species. In guinea pigs, but less so in rats, the observed changes in activity were usually modulated by intermittency. Increases in hematocrit, organ protein, and lung DNA, which may also reflect ongoing oxidative damage, were also slowed with intermittency in guinea pigs. Intermittency benefited both species by postponing gross symptoms of toxicity, but its modulation of changes in enzyme activities and other biochemical variables was more pronounced in guinea pigs than in rats, suggesting that there are additional mechanisms for tolerance.     

Regional lipid peroxidation and protein oxidation in rat brain after hyperbaric oxygen exposure

Reactive oxygen species may participate in development of neurological toxicity resulting from hyperbaric oxygen exposure. To explore the possibility that increased reactive O₂ metabolite generation may result in oxidative modification of lipids and proteins, rats were exposed to five atmospheres (gauge pressure) of O₂ until development of an electroencephalographic seizure. Lipid peroxidation (as thiobarbituric acid-reactive substances) and protein oxidation (as 2,4-dinitrophenyl-hydrazones) were measured in five brain regions. Oxidized and reduced glutathione were also determined because of their role in regulating lipid peroxidation. Lipid peroxidation was confined to the frontal cortex and hippocampus, while protein oxidation (in both cytoplasmic and membranous fractions) and increased oxidized glutathione was evident throughout the brain. These results support a role for formation of reactive O₂ metabolites from hyperbaric O₂ exposure and suggest that protein oxidation, especially in soluble proteins, may be one of the most sensitive measures.     

An analysis of decrements in vital capacity as an index of pulmonary oxygen toxicity

Decrements in vital capacity (% delta VC) were proposed by the Pennsylvania group in the early 1970s as an index of O2-induced lung damage. These workers used the combined effects of PO2 and time of exposure to develop recommendations to limit expected % delta VC. Adopting this general approach, we fitted human pulmonary O2 toxicity data to the hyperbolic equation % delta VC = Bs.(PO2 - B1).(time)B3 using a nonlinear least squares analysis. In addition to the data considered in 1970, our analysis included new data available from the literature. The best fit was obtained when 1) an individual slope parameter, Bs, was estimated for each subject instead of an average slope; 2) PO2 asymptote B1 = 0.38 ATA; and 3) exponent B3 = 1.0. Wide individual variation imposed large uncertainty on any % delta VC prediction. A 12-h exposure to a PO2 of 1 ATA would be expected to yield a median VC decrement of 4%. The 80% confidence limits, however, included changes from +1.0 and -12% delta VC. Until an improved index of pulmonary O2 toxicity is developed, a simplified expression % delta VC = -0.011.(PO2 - 0.5).time (PO2 in ATA and time in min) can be used to predict a median response with little loss in predictability. The limitations of changes in VC as an index are discussed.