Lethal physiological effects of carbon dioxide exposure at high concentration in rats

The acute toxicity of high concentrations of carbon dioxide (CO₂) was investigated in anesthetized rats using physiological parameters. At an oxygen concentration of 21%, the survival time decreased in a concentration-dependent manner from ≥7.3 h at 20% CO₂ to 1.0 h at 50% CO₂. The animals were divided into groups that were exposed to 40% CO₂ and 21% O₂ balanced with nitrogen (CO₂ group), 40% CO₂ and 12.6% O₂ (CO₂-Hypoxia group), 0% CO₂ and 12.6% O₂ (Hypoxia group), and 0% CO₂ and 21% O₂ (Control group) for 3 h. In the CO₂ group, mean blood pressure (MBP) increased temporarily in the first 60 min followed by a gradual decrease, while breathing rate (BR) decreased immediately up to 3 h and the concentration of serum indicators reflecting organ damage increased. Most of these effects progressed in the CO₂-Hypoxia group. The Hypoxia group showed a contrasting response to the CO₂ groups in MBP and BR, and a slight partial increase in the serum indicators. Histological changes were not observed in any primary organs of any group, except for eosinophilic or necrosis of pyramidal cells in the hippocampal CA1 region of the CO₂ group. These results indicate that high concentrations of CO₂ inhalation are toxic, likely due to BR suppression, and that hypoxia produced under a high CO₂ environment, while showing little effect on its own, enhances the toxic effects of CO₂.