Cardiorespiratory effects following acute exposure to pyridostigmine bromide and/or n,n-diethyl-m-toluamide (deet) in rats (2001).

Content Provider	CiteSeerX
Author	Rockhold, Robin W. Hume, Arthur S. Chaney, Leslie A.
Abstract	The acute lethal interaction that occurs in rodents when high doses of a peripherally restricted cholinesterase inhibitor, pyri-dostigmine bromide (PB), and the insect repellent N, N-diethyl-m-toluamide (DEET) are combined was rst described during stud-ies of chemical mixtures that were targeted as potential causative agents of GulfWar illnesses. This study was intended to provide in-sight into possible mechanisms of that lethal interaction. Following a single intraperitoneal injection of PB (2 mg/kg) and/or DEET (300 or 500 mg/kg), respiratory activity was measured in con-scious freely moving rats using whole-body plethysmography. Car-diovascular function was also monitored simultaneously through an arterial catheter. PB (2 mg/kg) given alone stimulated respi-ration and increased blood pressure. Arterial pH levels were de-creased, whereas pO2 and pCO2 remained at control levels. Ad-ministration of DEET (300 mg/kg) alone increased tidal volume and decreased blood pressure. Blood gases and pH levels were un-altered.A higher dose of DEET (500 mg/kg)alsodecreased respira-tory and heart rate. Coadministration of PB (2 mg/kg) and DEET (300 mg/kg) increased tidal volume, decreased arterial pH, and ele-vated pCO2. Heart rate and blood pressure declined progressively after drug coadministration. Pretreatment with atropine methyl nitrate (AMN), a peripherally selective competitive antagonist at nicotinic and muscarinic receptor sites, reduced the individual ef-fects of PB or DEET, and signi cantly increased survival after co-exposure to these agents. Although changes in respiratory function may have contributed to the lethal interaction, it was concluded that the primary cause of death was circulatory failure.
File Format	PDF
Publisher Date	2001-01-01
Access Restriction	Open
Content Type	Text