Toxic doses of paraoxon alter the respiratory pattern without causing respiratory failure in rats

Respiratory failure, through a combination of muscarinic, nicotinic, and central effects, is the primary cause of death in acute organophosphate poisoning. However, the mechanisms inducing respiratory failure remain unclear. In rats poisoned subcutaneously with paraoxon at doses near the LD50, we studied the pattern of respiration using whole body plethysmography and the occurrence of respiratory failure using arterial blood gases. Subsequently, we studied the effects of atropine on paraoxon-induced modification of ventilation and arterial blood gases. Fifty and 75%, but not 10% of the subcutaneous LD50 of paraoxon induced marked and sustained signs and symptoms. At 30 min post-injection and throughout the study, there was a significant decrease in the respiratory frequency (34% (50% versus solvent), and 29% (75% versus solvent)) and a significant increase in the expiratory time (72% (50% versus solvent) and 60% (75% versus solvent)) with no modifications of the inspiratory time. The tidal volume was significantly increased for the 75% but not for the 50% dose. Apnea was never detected. Even at the 75% dose, paraoxon had no effects on PaO2, PaCO2 or HCO3−; however, a significant decrease in arterial pH was observed at 30 min (7.34 ± 0.07 versus 7.51 ± 0.01, p = 0.03). Atropine completely reversed the paraoxon-induced respiratory alterations. We conclude that paraoxon, at doses equal to 50 and 75% of the LD50, alters ventilation at rest without inducing respiratory failure during the study period.