High-dose intravenous paraoxon exposure does not cause organophosphate-induced delayed neuropathy (OPIDN) in mini pigs

Organophosphorus compounds are inhibitors of serine hydrolases. Some of the se compounds produce, in addition to their high acute toxicity, a more pers istent effect: organophosphate-induced delayed neuropathy (OPIDN). The puta tive molecular entity whose inhibition is thought to be responsible for OPI DN is the neuropathy target esterase (NTE). Although in vitro NTE is resist ant to paraoxon (PX), occasional case reports have associated PX with OPIDN . To assess clinically whether or not high-dose i.v. PX causes OPIDN in mini pigs, 14 mini pigs were anaesthesized, intubated and mechanically ventilate d. In a first set of experiments eight pigs received I mg PX kg(-1) body we ight (BW) dissolved in alcohol. Two control animals received alcohol in a c orresponding amount. After infusion of PX, survival of the animals during t he acute phase of intoxication was achieved by intensive-care support, usin g appropriate drugs and fluids according to a pre-established protocol. The mini pigs were extubated 1036 +/- 363 min later (mean SD). The pigs were o bserved prior to PX application and for 6 weeks thereafter for any abnormal ities and/or signs of OPIDN, such as leg weakness, ataxia and paralysis. Ob servations were graded on a scale for three categories (position, motor def iciency, reaction), with a maximal cumulative score of 9. In a second set o f experiments (four additional pigs) larger PX doses were used (3, 9, 27 an d 81 mg kg(-1) BW). After recovering from general anaesthesia/surgery, within 2 weeks all anima ls reached the initial score on the scale. It can be concluded that high-do se i.v. PX exposure does not induce OPIDN in mini pigs during the 6-week ob servation period. Copyright ((C) 2001 John Wiley & Sons, Ltd.