CARDIORESPIRATORY EFFECTS OF O-ISOBUTYL S-[2-(DIETHYLAMINO)-ETHYL]METHYLPHOSPHONOTHIOATE - A STRUCTURAL ISOMER OF VX

O-Isobutyl S-[2-(diethylamino)ethyl]methylphosphonothioate (VR) is a s tructural isomer of a more well-known chemical warefare agent, O-ethyl S-[2(diisopropylamino)ethyl]methylphosphonothioate (code designation VX). In this study, cardiorespiratory and central nervous system (CNS) effects of VR (2LD(50) or 22.6 mu g kg(-1); s.c.) were evaluated in u rethane-anesthetized (Group 1) and unanesthetized (Group 2) guinea pig s instrumented for concurrent recordings of electrocorticogram (ECoG) and a variety of cardiorespiratory activities. The first sign of intox ication was a state of progressive bradycardia, vascular hypotension a nd arrhythmia (Group 1, similar to 13 min post-VR; Group 2, similar to 6 min post-VR). Bradypnea, excessive salivation and compensatory chan ges in blood pressure typically did not emerge until 3-5 min prior to apnea (Group 1, similar to 28 min post-VR; Group 2, similar to 15 min post-VR). An idioventricular rhythm, which signalled a failing myocard ium, appeared at the same time or shortly after the development of a b radypneic profile. Another notable toxicity component of VR, based on arterial pH, pO(2)/pCO(2) and bicarbonate (HCO3-) level data, was a st ate of combined hypercapnia, acidemia and hypoxemia during the develop ment of bradypnea. Taken together, findings from this study indicated that changes in medullary respiratory unit activity and ECoG data disp layed little, if any, notable signs of CNS perturbation prior to the t erminal stage (similar to 1 min prior to respiratory failure). Thus, i n addition to displaying a greater sensitivity to perturbation by VR, the peripheral cardiorespiratory system components also appeared to pl ay a more important role in precipitating a progressively dysfunctiona l cardiorespiratory status that ultimately led to collapse of central respiratory mechanisms and death. (C) 1998 John Wiley & Sons, Ltd.