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Cardiorespiratory effects of O ‐Isobutyl S‐[2‐(diethylamino)‐ethyl] methylphosphonothioate – a structural isomer of VX
Author(s) -
Chang F.C. T.,
Gouty S. C.,
Eder L. C.,
Hoffman B. E.,
Maxwell D. M.,
Brecht K. M.
Publication year - 1998
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/(sici)1099-1263(1998090)18:5<337::aid-jat518>3.0.co;2-g
Subject(s) - cardiorespiratory fitness , chemistry , cardiology , medicinal chemistry , medicine
O ‐Isobutyl S ‐[2‐(diethylamino)ethyl]methylphosphonothioate (VR) is a structural 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 μg kg −1 ; s.c.) were evaluated in urethane‐anesthetized (Group 1) and unanesthetized (Group 2) guinea pigs instrumented for concurrent recordings of electrocorticogram (ECoG) and a variety of cardiorespiratory activities. The first sign of intoxication was a state of progressive bradycardia, vascular hypotension and arrhythmia (Group 1, ˜ 13 min post‐VR; Group 2, ˜6 min post‐VR). Bradypnea, excessive salivation and compensatory changes in blood pressure typically did not emerge until 3–5 min prior to apnea (Group 1, ˜28 min post‐VR; Group 2, ˜15 min post‐VR). An idioventricular rhythm, which signalled a failing myocardium, appeared at the same time or shortly after the development of a bradypneic profile. Another notable toxicity component of VR, based on arterial pH, p O 2 / p CO 2 and bicarbonate (HCO 3 − ) level data, was a state of combined hypercapnia, acidemia and hypoxemia during the development of bradypnea. Taken together, findings from this study indicated that changes in medullary respiratory unit activity and ECoG data displayed little, if any, notable signs of CNS perturbation prior to the terminal stage (∼1 min prior to respiratory failure). Thus, in addition to displaying a greater sensitivity to perturbation by VR, the peripheral cardiorespiratory system components also appeared to play a more important role in precipitating a progressively dysfunctional cardiorespiratory status that ultimately led to collapse of central respiratory mechanisms and death. © 1998 John Wiley & Sons, Ltd.