Dichloroacetate treatment of patients with severe lactic acidosis results in statistically significant but clinically unimportant changes in arterial-blood lactate concentrations and pH and fails to alter either hemodynamics or survival.

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Exposure of rats to 100% O2 at high pressure (greater than 2.0 ATA) results in generalized convulsions and death within several hours. The tripeptide, glutathione, has been shown to protect rats exposed to hyperbaric hyperoxia with delayed onset of seizures and prolonged survival. To investigate the hypothesis that glutathione exerts its protective effects via the glutathione redox cycle, we injected selenium-deficient rats and their selenium-supplemented controls with either glutathione (1 mmol/kg) or an equivolume of saline before exposure to 100% O2 at 4 ATA. Selenium-deficient rats exhibit marked reduction in liver glutathione peroxidase activity (GSH-Px). Glutathione administration significantly delayed both the onset of seizures and time to death in the control animals. In selenium-deficient rats, however, glutathione administration was not protective, having no significant effects on time to seizure or time to death. We also measured changes in glutathione concentrations in lung, liver, and brain of these same groups of animals exposed either to hyperbaric hyperoxia or to room air. In control rats, lung and brain glutathione concentrations did not change with the hyperbaric exposure regardless of glutathione pretreatment status, but hepatic glutathione concentration declined significantly during the exposure when glutathione was not supplied. If these animals were pretreated with glutathione, the decline in hepatic glutathione concentrations did not occur. In selenium-deficient rats, the hyperbaric exposure did not result in changes in lung, brain, or liver glutathione concentrations either in the glutathione-pretreated or in the saline-pretreated animals. Exogenous GSH administration does not protect selenium-deficient rats from hyperbaric hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

The administration of very low doses of bacterial endotoxin protects rats during exposure to hyperoxia and is associated with the induction of lung antioxidant enzyme activities. Copper-deficient rats have increased susceptibility to O2 toxicity, which may be related to their decreased lung superoxide dismutase activity (SOD) or decreased plasma ceruloplasmin concentrations. To determine whether endotoxin can protect against hyperoxia in this susceptible model, we exposed copper-deficient and control rats to a fractional inspiratory concentration of O2 greater than 0.95 for 96 h after pretreatment with 500 micrograms/kg of bacterial endotoxin or phosphate-buffered saline (PBS). Mortality in the copper-deficient and control rats given PBS and exposed to O2 for 96 h was 100%. Copper-deficient rats died significantly earlier during the exposure than controls. No mortality occurred in either group treated with endotoxin and hyperoxia despite the decreased activity of copper-dependent enzymes in the copper-deficient rats. Copper-deficient rats treated with endotoxin and exposed to hyperoxia did increase lung Cu-Zn-SOD activity, but activity remained below levels found in air-exposed controls. Mn-SOD activity was found to be induced above air-exposed controls in the copper-deficient rats treated with endotoxin and exposed to hyperoxia. Hyperoxic exposure resulted in a marked increase in plasma ceruloplasmin concentrations in the control rats, but no increases in ceruloplasmin occurred in the copper-deficient animals. Endotoxin protects copper-deficient rats from hyperoxia despite their decreased lung Cu-Zn-SOD activity, and decreased plasma ceruloplasmin.