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 LD(50), 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 LD(50) of paraoxon induced marked and sustained signs and symptoms. At 30min 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 PaO(2), PaCO(2) or HCO(3)(-); however, a significant decrease in arterial pH was observed at 30min (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 LD(50), alters ventilation at rest without inducing respiratory failure during the study period.
Villa
Antoine F
AF
INSERM U705, CNRS UMR 7157, Université Paris 5, Hôpital Fernand Widal, 75010 Paris, France.
Houze
Pascal
P
Monier
Claire
C
Risède
Patricia
P
Sarhan
Hala
H
Borron
Stephen W
SW
Mégarbane
Bruno
B
Garnier
Robert
R
Baud
Frederic J
FJ
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001784:Blood Gas Analysis; D002245:Carbon Dioxide / Q000097:blood; D002802:Cholinesterases / Q000097:blood; D004347:Drug Interactions; D007306:Insecticides / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010261:Paraoxon / Q000633:toxicity*; D010993:Plethysmography, Whole Body; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000097:blood / Q000139:chemically induced
D007306:Insecticides; D018727:Muscarinic Antagonists; D002245:Carbon Dioxide; D001285:Atropine; D002802:Cholinesterases; D010261:Paraoxon; D010100:Oxygen